Technology for “actionable insights”: Dr Nicolas Gaudenzio

Technology for “actionable insights”: Dr Nicolas Gaudenzio

Next up in our exciting Congress Conversations series is an interview with Genoskin’s Dr Nicolas Gaudenzio. He joined us at the Congress for a technology showcase, presenting on optimising vaccine candidate selection with an “insight into VaxSkin’s human skin-based multimodal immune profiling system”. We are glad that he was able to make some time to share some information on the work his team is doing to revolutionise vaccine discovery and development, and we hope that you enjoy the interview!

Introducing Dr Gaudenzio

Dr Gaudenzio explains that he is the Chief Scientific Officer at Genoskin and Principal Investigator at Inserm. Genoskin is a French-American biotech company based in Toulouse and Salem.

“We have built a network of surgeons in hospital in Europe and in the US and we actually obtain donated human skin samples that we preserve alive, in a culture dish, and that we use actually to test the safety and efficacy of different drugs that would be administered through the subcutaneous route.”

 

What happens at the site of injection?

We asked Dr Gaudenzio to give us an insight into what actually happens at the site of injection and how this informs the work that Genoskin is doing. He explains that how we currently “assess” and “study” the effects of vaccination in people is through a blood draw, days or weeks after an injection, to examine the presence of antibodies or antigen-specific immune cells.

“But what’s going on actually at the site of injection, when we inject the vaccine, it’s still a black box.”

Genoskin, therefore, tests vaccines in donated skin samples. The team injects vaccine candidates into “samples from multiple donors” to “reproduce the heterogeneity of the population”. This allows them to understand two things: “what’s going on at the tissue level and then what’s going on at the single cell level”. At tissue level, they can understand the risks of the vaccine and how it will “modify the skin ecosystem”. At single cell level they can understand the type of immune cells that uptake the vaccine, how it’s received, and how this uptake will activate specific cells.

“And so we mix different technologies; we mix some transcriptomic analyses, proteomic analyses, and we integrate all those data with some AI and machine learning systems to better understand and get really actionable insights.”

For more on the technology and its applications you can visit Genoskin’s website here.

 

Why does this matter?

If this technology is new to you, questions about the benefit might arise. We asked how this approach is different, and better, than other, more ‘traditional’ approaches. Dr Gaudenzio suggests that the data are “100% human”. Therefore, they do not “extrapolate data from animal studies”. This has several benefits, not only for the animals; the team gets the “true reaction” that would happen in the human organ.

“This is a very valuable information because there is always a gap between when we finish the animal studies and then we go into the clinic, what’s going to happen in the patients?”

The “opportunity” that is offered by Genoskin’s technology is a “fully immunocompetent organ” that provides “a lot of information” so we can predict what will happen in the patient.

 

How receptive is the community?

When we consider these innovative technologies, a question that often springs to mind is about the reception they might get from the established vaccine community. We asked Dr Gaudenzio about entering the space and offering new solutions; how easy or hard is it? He suggests that this community is “experiencing the same problem”: “how do we translate animal studies into prediction for humans”? Different approaches are being explored, but none offer the “solution that is needed”. Indeed, “people are also coming to us directly” to discuss collaboration.

“Something very unique, I think of our approach, is to be able to study our immune system, the human immune system, in its native environment…I think this is something very valuable, and it seems to be appreciated so far by the community!”

 

Why WVC?

Our final question, as always, gives our experts an opportunity to share what they are looking forward to at the event.

“I’m looking forward to exchange with many people!”

Not only that, Dr Gaudenzio, like other speakers, was looking forward to enjoying our beautiful Spanish setting.

 

We hope that the Congress was fruitful for Dr Gaudenzio, and that you enjoy learning more about his work! Thank you to Dr Gaudenzio for his time and insight. For more like this, don’t forget to subscribe here.

Dynamics of nAbs: progress towards HIV-1 vaccine in research

Dynamics of nAbs: progress towards HIV-1 vaccine in research

A team of researchers shared in November 2023 that their study, published in Nature Medicine, has provided insight into the longevity of neutralising antibodies (nAbs) in HIV-1 infected people. Despite the assumption that an HIV-1 vaccine “can only be effective” if it produces these antibodies in vaccinated people, no neutralising antibody-eliciting vaccines are yet available. Therefore, only data from “HIV-1 neutralisers – persons with HIV-1 who naturally develop broad and potent nAbs – can inform” research.  

The team therefore assessed HIV-1-neutralising immunoglobulin G (IgG) from 2,354 persons with HIV-1, either on or off antiretroviral therapy. The results indicate that these responses can persist for “several years”, even at low antigen levels, from which the researchers infer that an HIV-1 vaccine “may elicit a durable nAb response”.  

Getting to know nAbs  

The authors state that neutralising antibodies (nAbs) block viral infection by “directly binding circulating viruses, thus preventing these viruses from infecting their intended target cells”. Furthermore, they can “eliminate infected cells” through “antibody-mediated effector functions”. Therefore, they are “crucial” to “preventing and overcoming viral infections” and are considered “one of the most important correlates of vaccine-mediated protection”.  

In HIV-1 infection, elicited circulating antibodies are reportedly “mostly strain-specific” and unable to prevent replication of the “broad diversity of viral strains” that evolves in a person who is infected with HIV-1. However, broadly neutralising antibodies (bNAbs) targeting “up to 99% of tested HIV-1 variants” have been isolated from persons with an “extraordinary HIV-1 neutralising serum response. The authors refer to “elite neutralisers”, with “elite activity” previously defined as the “ability to neutralise, on average, more than one pseudovirus at an IC50 titer of 300 within a clade group and across at least four clade groups”.  

These bNAbs have shown an ability to prevent infection in mice and nonhuman primate models. Additionally, research into two multicentre trials revealed that intravenous infusions of the bNAb VRC01 were “associated with reduced incidence of infection by VRC01-sensitive HIV-1 strains”. Despite this, there was no greater protection from HIV-1 acquisition overall in comparison with placebo. It is understood that “serum titers and the potency against infecting strains of passively infused bNAbs correlate with protection from HIV-1 infection”.  

What does this mean for vaccines? 

Considering available research, the authors suggest that a vaccine that can elicit “potent and borad nAbs in humans at high titers could effectively protect from HIV-1 infection”. Thus, the induction of nAbs is a “main goal” for vaccine development. The paper recognises the development of “several” vaccine candidates and strategies. However, there are challenges to overcome, and information on the “durability and dynamics” of nAb responses in humans will be “highly relevant” for these strategies.  

What does the study do? 

The paper explores the results of the “largest international study” of HIV-1 neutralisation dynamics, sampling over 2,300 individuals. Through IgG isolation, the team “determined the neutralising activity” in participants on and off ART, assessing the “association between different levels of viral replication” and nAb responses.  

Consequently, they 

  1. Determine factors driving IgG-neutralising activity 
  2. Describe the neutralisation activity of highly potent elite neutralisers  
  3. Longitudinally decipher the nAb activity in response to different viral load dynamics 
Study findings and implications 

The authors suggest that for “many” infections and vaccines the dynamics of nAb responses are “well-studied” and knowledge about nAb durability can inform vaccination regimens. However, in the absence of an effective HIV-1 vaccine and considering that “only a few people develop a potent neutralising response” during natural infection, knowledge about the “durability of naturally developing anti-HIV-1 nAb responses” is “missing”. While there are “promising” candidates in development, it is “unclear” how long vaccine-induced nAb responses would last and offer protection.  

In the cohort, involving HIV-1-infected persons from “various countries” (Cameroon, Germany, Nepal, and Tanzania), the researchers identified “several factors” as “independent predictors for better IgG neutralisation”. To understand the changes in nAb response over time in response to different levels of viral replication, they conducted a longitudinal study of individuals with potent HIV-1-neutralising IgG activity.  

The nAb half-lives in individuals with no- and low-level viraemia were 9.3 years and 16.9 years. At 4.0 years, half-life was “considerably shorter” in individuals who initiated ART and therefore experienced a suppression of their viraemia during the follow-up period. Thus, neutralising serum responses are “relatively stable” over time, even without “large amounts of stimulating antigen”.  

“If effective nAb-inducing vaccines are available in the future, our data indicate that nAbs can be rather long-lived even if the vast majority of the stimulating antigen vanishes over time.”  

We’re looking forward to more on the development of HIV vaccines at the Congress later this month; will you join us there? If you can’t make it, why not subscribe for more research insights and updates.

Study: how might a Strep A vaccine reduce antibiotic use?

Study: how might a Strep A vaccine reduce antibiotic use?

As the threat presented by antimicrobial resistance (AMR) grows globally, the pressure is mounting on the vaccine community to continue contributing to the “toolkit” against AMR. A recent study in eBioMedicine suggests that an effective vaccine against group A Streptococcus (Strep A) could “avert 2.8 million courses of antibiotics” for sore throat treatment in children. This would increase to an “estimated 7.5 million” courses averted if an effective vaccination programme “also reduced precautionary prescribing”.  

Strep A and AMR 

The authors state that infection by Streptococcus pyogenes, also known as group A Streptococcus or Strep A, is the “most common bacterial case of sore throat”; more than 600 million cases are identified each year worldwide. These infections can cause “severe clinical sequelae” like streptococcal toxic shock syndrome, sepsis, or acute post-streptococcal glomerulonephritis.  

Although accurate diagnosis and treatment of Strep A sore throat is “known” to reduce the risk of developing acute rheumatic fever (ARF) and may reduce the risk of other sequelae, “most sore throats are caused by viral infections”, where antibiotics are “ineffective”.  

“Difficulties in clinically discriminating between pharyngitis due to Strep A and other pathogens, along with the time and cost associated with performing and processing a diagnostic test, means that many patients are prescribed antibiotics either without testing or before the test result is known.”  

Furthermore, in low-resource settings tests are not always readily available, practical, or affordable. Therefore, there is cause for concern that the frequency of antibiotic prescriptions exceeds the necessary number.  

“Inappropriate and excessive antibiotic consumption is a major contributor to AMR.”  

AMR “reduces antibiotic effectiveness, worsens patient outcomes, and increases treatment costs” with a particular burden borne in lower-resource settings. The study suggests that immunisation with a future Strep A vaccine could prevent necessary prescription of antibiotics for sore throat by preventing Strep A infection and will “likely reduce unnecessary prescription”. Therefore, the development of a vaccine is a “global priority”.  

How important would a vaccine be? 

The authors believe that understanding the “full scope of antibiotic consumption” for sore throat is “a key part of understanding the potential value” of a vaccination programme. The study sought to: 

  1. Estimate the mean rate and total number of antibiotic courses prescribed to treat sore throat 
  2. Estimate the proportion of prescriptions for sore throat that is attributable to treatment of sore throat caused by Strep A 
  3. Summarise the distribution of antibiotic classes prescribed for sore throat 
  4. Explore the potential reduction in antibiotic prescribing for sore throat due to implementation of prospective Strep A vaccines 

The team reviewed and analysed articles published between January 2000 and February 2022 with reference to antibiotic prescribing or consumption, sore throat, pharyngitis, or tonsillitis. They then calculated the estimated reduction in antibiotic prescribing due to the introduction of Strep A vaccines by combining these analyses with assumptions for the effectiveness, duration of protection, and coverage of a vaccine.  

From 101 studies across 38 countries the mean prescribing rate for sore throat was “approximately 5 courses per 100 population per year”, accounting for “approximately 5% of all antibiotic consumption”.  

“Based on 2020 population estimates for countries with empiric prescribing rates, antibiotic consumption for sore throat was estimated to exceed 37 million courses annually, of which half could be attributable to treatment for Strep A.” 

The study suggests that a vaccine that reduces infection rates by 80%, with 80% coverage and a 10-year duration of protection, could avert over 2.7 million courses of antibiotics in 5 to 14-year-olds. A key finding of the study was a lack of published research from low- and middle-income countries, where Strep A disease and complications are “much higher”.  

“Understanding sore throat-based antimicrobial use in these countries is critical and may be a major driver of AMR. Equally, the impact of a Strep A vaccine may be even more dramatic in such settings.” 

The paper recognises that there is “little empirical data” to estimate the consumption of antibiotics due to sore throat, nor the proportion that is attributable to Strep A infection. These data are “crucial” to understanding the effects of Strep A vaccination, beyond a direct reduction in infections, the “economic and societal value”.  

How do you think a vaccine could transform Strep A-associated antibiotic use? Do check out the full paper here and don’t forget to subscribe for more research insights.

“We know what works”: the “last mile” with Dr Angus Thomson

“We know what works”: the “last mile” with Dr Angus Thomson

With the Congress in Barcelona firmly behind us we are able to reflect on the key themes and discussions that took place. Such a theme was undoubtedly sparked by Dr Angus Thomson who led our Vaccine Hesitancy and Misinformation workshop on the pre-Congress workshop day. We were lucky to catch him the day after this to hear about what went on and what he is taking away from the event. Thank you to Dr Thomson for his time and insight, and we hope that you enjoy the conversation!

Introducing Dr Thomson

Dr Thomson is “trained as a molecular geneticist” but is now working in behavioural and social sciences, particularly as pertaining to “vaccine behaviours”. During the pandemic he served as a senior technical advisor to UNICEF, and has since established a behaviour design consultancy, called Irimi. Irimi’s approach is “listen to understand people’s lives”, and we’ll explore this in greater detail later on.

 

What did the workshop cover?

If you weren’t able to join the workshop, Dr Thomson explores some of the key ideas that were covered in this next segment. He reflects that the session was full of insights and attendees engaged with the key theme of the panel: getting on the “front foot”. For Dr Thomson, this means institutionalising the work that has been done to encourage public trust in vaccines.

“We’re always on the back foot; we’re always playing catch up, whether it’s in a pandemic or in our routine programmes.”

What the workshop highlighted were a “serious of mechanisms” with “strong science” behind them. Therefore, we can design “human-centred” and more effective interventions. When he speaks of effectiveness, Dr Thomson refers both to “public trust” and getting people vaccinated.

“The theme that emerged from yesterday’s discussion was: we know what works now. We invest billions of dollars in solid cold chain and vaccine delivery mechanisms, in discovery and clinical development, in bringing vaccines to market. But this last mile, or in many ways it’s like the last millimetre in people’s heads, of vaccine delivery, is the forgotten child of vaccination.”

During the pandemic, we saw the consequences of “failure to secure public trust” before vaccine introduction; Dr Thomson describes this as “disastrous” in many settings.

 

Listening, listening, listening

If you’ve encountered Irimi before, or perhaps you’ve checked out their website today, you’ll notice an emphasis on listening. We asked Dr Thomson to explain the significance of this.

“So, social listening is fundamental.”

With an understanding of “what’s driving people’s decisions” we can “design programmes that respond to those barriers or levers”, whether they are psychological, social, or even logistical. Dr Thomson refers to Dr Joe Smyser, from Public Good Projects, as an example of social listening to inform practices.

“Social listening is often confused with social media listening, and it’s not.”

Dr Thomson highlights that much of the world is “digitally disenfranchised” so social listening must be flexible to all avenues of social communication. For example, television or radio, are examples of offline communication that many people access. Social listening is “fundamental” to vaccine demand strategies.

“Any strategy should be underpinned by a solid social listening programme. That programme allows you to… not just detect mis- and disinformation but to be able to tune into people’s questions and concerns, understand the information they’re looking for, and therefore provide that to them.”

 

Offline communities and a call to action

After Dr Thomson mentioned “digitally disenfranchised” communities we were curious about how easy it is to engage in, or implement, social listening programmes in these communities. Interestingly, he suggests that, despite the “standard thinking”, many countries already have “very strong networks” within communities already.

“The challenge is, countries need to build a strategy for this, a strategy that fits within the current programme…it actually needs to become institutionalised.”

Dr Thomson emphasises that “we will never stop having crises of confidence or just key questions that arise”. For him, the “only” response is rooted in understanding, to which a national social listening programme is “fundamental”. Then, the next steps are using the behavioural insights to inform behavioural interventions and “wrapping all of that into a broader strategy”.

Looking back to the workshop, Dr Thomson identifies some key themes. The first is “dialogue”.

“It must be dialogue; it can’t be one way communications”.

Another theme is “empirical” data, the social and behavioural insights that are revealed. Finally, collaboration is key.

“No single vaccination programme can be expected to be doing everything that is needed to sustain high coverage, high immunisation rates in all of their programmes.”

For Dr Thomson, some of the “best examples” are partnerships or coalitions involving academics, the private sector, or civil society. These come together and “coordinate” a strategy.

“There was almost a call to action yesterday to many of the attendees, to be thinking about what their organisation can be contributing to this. It’s not something you can leave in the lap of a programme, which is usually overworked and understaffed.”

Partnerships bring resources and “mobilise and align actions”, and have an effect on both trust and uptake.

 

The media

With varying levels of engagement and trust in the media during the pandemic, we asked Dr Thomson about how the vaccine community can effectively support media outlets and ensure that vaccine information is effectively and accurately reported. He defers to Apoorva Mandavilli, who spoke during the workshop, making a “very clear request” for “more information, more data, and the provision of that in a transparent way”.

Dr Thomson emphasises that “journalist are fundamental”. Although some media outlets have lost trust, there are still “key” outlets that provide essential information. Journalists working at these outlets “consistently” ask for more information, both during pandemics and not. However, some health authorities were “opaque” in sharing data.

“Risk communication is a science and we know what works, and it is underpinned by the principle of transparency; you say what you know; you say what you don’t know, and you say it very, very regularly.”

This principle was applied “differently” during the pandemic, with “dramatic” results. A study that Dr Thomson refers to highlights this, demonstrating that “public trust” in institutions correlated with vaccine uptake. Therefore, the national health response of different countries had a “differentially positive or negative” effect, and we are now catching up.

 

Why WVC?

As with all of our speakers, we asked Dr Thomson what his hopes for, or highlights of, the Congress are. He suggests that everyone has “our own agenda”. For him, that involves several things, including understanding the “great and very exciting work” that is taking place across the vaccine environment.

“As a biological scientist it’s the most exciting period in my whole career!”

However, “we can’t continue to forget” the last stage of vaccine delivery: building public trust. For him, the “reality is” that technology is “unlikely to transform public trust”.

“It takes strategy; it takes investment; it takes a programme at a national and subnational level in every country. We know what works…I guess we’re here trying to mobilise people to be thinking through what is the role they can play, at an individual or an organisational level, to be supporting this crucial part of vaccination programmes across the world.”

If you encountered Dr Thomson we are confident that he mobilised you in this way, and we hope that he had a productive time with us in Barcelona. Thank you to Dr Thomson for his contribution to the Congress Conversations series, and we hope that you enjoyed his insights. For more conversations like this one, don’t forget to subscribe to our newsletter.

UK JCVI recommends routine childhood chickenpox vaccination

UK JCVI recommends routine childhood chickenpox vaccination

In November 2023 the UK’s Joint Committee on Vaccination and Immunisation (JCVI) announced that it was recommending a “universal varicella (chickenpox) vaccination programme” to be introduced as part of the routine childhood schedule. The programme would comprise 2 doses of the combined MMRV (measles, mumps, rubella, and varicella) vaccine, offered at 12 and 18 months. This recommendation follows the evidence from other countries that a 2-dose schedule decreases the number of varicella cases in childhood “rapidly and dramatically”.  

Chickenpox in childhood 

Varicella, known as chickenpox, is a “highly contagious infectious disease” caused by the varicella zoster virus. Symptoms include an itchy, spotty rash, a fever, and general malaise. JCVI states that it is a “very common” disease that “affects most children during childhood”. However, it can be caught at any age. It is transmitted through direct contact with infected people or through airborne droplets.  

Although most varicella cases in children are “relatively mild” and resolve without medical interventions, some children can develop complications such as bacterial infection of skin lesions, or encephalitis or pneumonitis. It is most serious in “very young infants” under the age of 4 weeks, and in adults. Data from the UKHSA suggest that “approximately half of children” have had varicella by the time they reach 4 years old; this increases to 90% by the age of 10. Thanks to COVID-19-related restrictions, fewer cases of varicella were identified; this leaves a “larger pool of children” susceptible.  

Herpes zoster, or shingles, is triggered when the varicella zoster virus is reactivated in a previously infected person. This is a risk because the virus remains dormant after an initial infection. People with herpes zoster can transmit the virus to susceptible people to cause chickenpox.  

What is currently in place? 

The JCVI reports that the UK has had a universal shingles vaccination programme in place since 2013 for adults. The programme was updated in September 2023 and includes: 

  • Adults turning 65 years of age 
  • Adults aged 70 and over 
  • Adults over the age of 50 with a severely weakened immune system” 

In 2009 the JCVI considered strategies to protect against varicella and herpes zoster, electing not to recommend varicella vaccination.  

“It was agreed at the time that this recommendation should be reviewed when further information relating to varicella epidemiology, vaccination, and exogenous boosting were available.” 
What’s changed? 

The varicella-zoster JCVI sub-committee has met “multiple times” over the past two years to review updated evidence on disease burden, potential effect on exogenous boosting, updated seroprevalence data, and modelling cost-effectiveness and real-world data from countries with programmes in place. The main JCVI then discussed these updates in October 2023.  

Disease burden 

The JCVI states that “errors in coding” confuse estimations of the true extent of hospitalisations caused by varicella. As hospitalisations are “frequently” due to secondary complications they are not always recorded as related to varicella. Furthermore, there may be other secondary complications that are less understood than the recognised cellulitis, invasive group A streptococcal infection, or childhood stroke. Complications from severe varicella are common, costly, and burdensome on health services.  

Real-world experience 

The JCVI can always draw on the experience of several countries with varicella vaccination in their routine vaccine schedules, such as the USA, Canada, Australia, and Germany. These countries have observed “significant” effects on cases and hospitalisations. Data were reviewed and incorporated into modelling work to investigate the “true extent” of the potential effect of vaccination on exogenous boosting.  

Cost-effectiveness modelling 

The JCVI sub-committee reviewed and provided input parameters for unpublished research carried out by the University of Cambridge. It was agreed that “previous assumptions” on the duration of protection from herpes zoster through exogenous boosting was too long. Cost-effectiveness analysis revealed that a routine childhood programme would be cost effective and possibly cost saving, depending on the vaccine price obtained.  

The recommended vaccination programme 

There were two options for varicella vaccination: a varicella-only product or as a combination with measles, mumps, and rubella, as MMRV. The proposed schedule involves two doses at 12 and 18 months. This coincides with times already reserved for the MMR vaccine according to upcoming changes to the routine infant schedule. This would mean that fewer injections are required per single immunisation visit, which is preferred among parents.  

JCVI recognises an “increased risk” of febrile seizures but describes the “absolute risk” as “very low”. This is “not of clinical concern” particularly in contrast to the “considerable benefit” of reduced injections.  

There is also potential to implement a catch-up vaccination programme, following the implementation of a routine programme. The committee considered this “beneficial” to prevent a gap in immunity. However, more work is needed to understand the cost-effectiveness of this programme.  

Does your country include varicella vaccination in routine childhood schedules? If not, would you like to see this change soon? For more on routine vaccination schedule updates, don’t forget to subscribe here.

NHS testing finds thousands of bloodborne virus cases

NHS testing finds thousands of bloodborne virus cases

In November 2023 the UKHSA and University of Bristol shared a report that reveals the results of an NHS England emergency department opt-out testing programme. The report was commissioned by NHS England to evaluate the first year of the programme, which tests for bloodborne viruses. It tests people in emergency departments who are having a blood test, regardless of symptoms. UKHSA states that this programme will increase diagnoses and treatment for HIV, hepatitis B, and hepatitis C, supporting elimination goals.  

Testing for BBV 

In April 2022 an NHS England funded programme of testing for bloodborne viruses (BBVs) in emergency departments (EDs) began. This was focused in “areas of very high diagnosed HIV prevalence” (5 or more people per 1,000 people between the ages of 15 and 59). Across 33 EDs 857,117 HIV tests, 473,723 hepatitis C virus (HCV) tests, and 366,722 hepatitis B virus (HBV) tests were conducted during the first year. 

“The scale of the programme makes it a substantial contribution to all BBV testing in England.” 

The report offers an interim public health evaluation from the first 12 months of the programme. Dr Sema Mandal, Deputy Director of Blood Safety, Hepatitis, STI, and HIV division at UKHSA, believes that the programme has already had a “significant” effect. The report “highlights how many people are living with an undiagnosed bloodborne virus.” 

“Fewer new diagnoses of HIV and hepatitis C were made compared to hepatitis B, highlighting the significant efforts and financial investment made to enhance diagnosis and treatment for HIV and HCV. Similar efforts are necessary for HBV to meet disease elimination targets.” 
Interim recommendations 

The following recommendations are offered. 

Delivery of testing: 
  • Develop and implement standard operating procedures (SOPs) for opt-out testing for all BBVs if these are not yet in place and ensure ED staff are fully briefed. 
  • Adopt opt-out procedures recommended as good practice, using verbal prompts where appropriate. 
  • Continue to work with electronic patient record (EPR) teams in sites that do not yet have automated test ordering in place to replicate approaches taken by other sites with high uptake. 
  • Develop procedures to contact individuals in the event of insufficient blood samples and to inform individuals if no BBV test has been performed. 
  • Continue to work with sites with low test uptake to understand barriers to testing and to facilitate higher testing rates. 
Linkage to care: 
  • Map and optimise care pathways for people newly diagnosed with HBV in ED as part of roll out of ED testing to new sites. 
  • Continue to improve linkage to care from ED by identifying the needs of individuals diagnosed in ED and structural facilitators to linkage to care, including additional interventions such as community support.  
  • Continue to share learning from different care pathways used within the programme. 
Evaluation and surveillance: 
  • Collaborate to increase recruitment of laboratories to SSBBV to improve representative coverage across sites, including those outside London.  
  • Work with laboratories to understand and address data incompleteness and recording of ED test setting SSBBV surveillance data. 
  • Investigate ways to identify confirmatory testing for HIV in SSBBV surveillance data.  
  • Undertake a deep dive with selected sites to understand why some people with positive HIV results are not matching to HARS and are not categorised as ED test setting.  
  • Work with HIV and sexual health clinics to improve recording of first site of HIV test to better understand the extent of ED testing nationally. 
  • Encourage sites to work with UKHSA on monitoring HBV linkage to care.  
What does the report conclude? 

The report states that the programme has demonstrated that opt-out ED BBV testing “can be delivered at scale” and “equitably”, despite large differences between sites. Although the programme has not yet reached the target of 95% of eligible people being tested, the data represent early stages.  

Identified issues include the confusion caused by a “no news is good news” approach, where individuals might assume that they have been tested. Therefore, sites are encouraged to develop procedures to “mitigate this risk”. The programme was “effective” at identifying new diagnoses for all 3 BBVs, the highest number being HBV. This high number has “implications of how to meet the increased need for HBV care when considering expansion”. Linkage to care is described as “sub-optimal” for all 3 BBVs, but more so for HBV and HCV than HIV.  

“There were limitations in the coverage and completeness of surveillance data for this evaluation.” 
Making contact count 

Matt Fagg, NHS England’s director for prevention and long-term conditions, said that “thanks to our routine opt-out testing programme” the NHS has been able to “identify and treat thousands more people” living with HIV and hepatitis.  

“Without this testing programme, these people may have gone undiagnosed for years, but they now have access to the latest and most effective life-saving medication.”  

The NHS, he says, is “committed to making all contact with patients count”. Public Health Minister Neil O’Brien agrees that the “amazing programme” is already making a “real difference”. He is “grateful” to the NHS for its “excellent work”. Professor Kevin Fenton, Chief Advisor on HIV and Chair of the HIV Action Plan Implementation Steering Group reflected that the “flagship initiative” is effective in “identifying people living with undiagnosed HIV” so they can be “signposted to support and treatment”.  

“While we know there are improvements to be made, this data gives us confidence that this essential part of our strategy is working. It’s crucial that we continue scaling up HIV testing, so people receive high quality care as we work towards ending HIV transmission in England by 2030.” 
Detecting silent threats 

Pamela Healy, Chief Executive of the British Liver Trust, described hepatitis B as an often “silent virus” with “thousands of people” in the UK unaware that they have it. If this virus is left undetected, it can cause liver damage or increase the risk of liver cancer.  

“It is crucial to find and provide treatment to these people to stop the virus causing further health issues and transmission.” 

Daniel Fluskey, Director of Policy at National AIDS Trust, suggests that “at least 340 people” who now know they are living with HIV can “access transformative treatment”. He encourages the NHS to take the “vital” lessons from the evidence to ensure that more people get diagnosed.  

Expansion plans  

Rachel Halford, The Hepatitis C Trust Chief Executive, commented that the pilot scheme has proven to be a “successful way to find people” who are living with HIV, hepatitis B, or hepatitis C. She offers the example of people who are experiencing homelessness and “only interact with healthcare services via emergency departments”. This scheme is a “great way to reach and treat these people”. 

“This life-saving initiative must now be expanded across the whole of the UK to ensure that everyone who is living with a bloodborne virus is found and offered treatment.”  

Anne Aslett, CEO at Elton John AIDS Foundation, reflected that “opt-out HIV testing works to diagnose HIV and find those who have dropped out of care” due to “stigma and other challenges facing treatment”. However, there are still 4,400 people who live with undiagnosed HIV, she suggests.  

“We need to ensure that we reach all communities across the country and roll out this successful method of HIV diagnosis to other high prevalence areas.”  

Richard Angell, Chief Executive of Terrence Higgins Trust, agrees.  

“It’s now time to urgently expand opt-out to more A&Es in England to change even more lives and ensure we make the rapid progress necessary to end new HIV cases by 2030.”  

For more on how vaccines and antiviral therapies can contribute to these goals, why not join us in Santa Clara for the Congress this month? If you can’t make it, do subscribe to our newsletters here.  

WHO commissions Vaccine Value Profiles for endemic pathogens

WHO commissions Vaccine Value Profiles for endemic pathogens

In what WHO is describing as a “significant stride towards facilitating and informing priorities in global vaccine development” it has commissioned 16 “Vaccine Value Profiles (VVPs)” to be published in Vaccine. This is a result of “collaborations” with pathogen and vaccine experts directed by the Product Development and Research team in WHO’s Immunisation, Vaccines & Biologicals department. The primary objective is the advancement of the development of vaccines for pathogens that “pose a substantial public health and socio-economic burden, especially in low- and middle-income countries (LMICs)”.  

What and why: VVPs 
“Despite the recognised public health need for vaccines against the most important pathogens causing disease and death, investment in research and development for many of these vaccines is hindered for reasons including challenging biological and technical feasibility, complex and costly pathways to regulatory approval and policy, and uncertain demand, impact, and uptake.”  

So begins the Vaccine Value Profiles editorial in the supplement. The authors suggest that the “hurdles” are “most detrimental” for vaccines without a “substantial high-income country market”, and for which “commitment to product development and commercialisation” relies on “clear articulation and quantification” of the value they bring to countries in need. They identify a need for this value assessment to begin at early development stage to ensure that products “with the greatest value to consumers are developed”.  

The intriguingly named “valley of death” between discovery and early clinical development must be avoided. Therefore, the WHO team encourages assessments of vaccine value through two main instruments: the Vaccine Value Profile and the Full Value of Vaccine Assessment (FVVA). The former uses a “templated format” to offer a consistent and holistic overview” of currently available data to define vaccine value for a specific pathogen. VVPs can identify research gaps that must be addressed to assess potential vaccine “impact” as part of an FVVA. 

WHO states that VVPs “serve as comprehensive summaries of critical evidence” that inform funding, research initiatives, and clinical and policy development strategies. They are “key resources for multiple stakeholders” in the vaccine community. For example, they are helping to direct Gavi’s Vaccine Investment Strategy (VIS), which we look forward to covering in our forthcoming interview with Gavi’s Dr Marta Tufet Bayona.  

What does the supplement offer? 

The special issue contains 16 VVPs for vaccines and prophylactic monoclonal antibodies against respiratory syncytial virus (RSV), Shigella, Enterotoxigenic Escherichia coli (ETEC), Group B Streptococcus, Salmonella paratyphi A., norovirus, Neisseria gonorrhoeae, cytomegalovirus (CMV), Chikungunya, invasive non-typhoidal Salmonella (iNTS), hookworm, leishmaniasis, schistosomiasis, malaria, tuberculosis, and herpes simplex virus (HSV).  

It will comprise two volumes, the first of which can be read here. Each profile has been developed by “globally diverse independent subject matter experts” according to the VVP template. The second volume is expected later this year. Dr Katherine O’Brien, Director of Immunisation, Vaccines & Biologicals at WHO, hopes to “leverage” lessons from the published profiles to “work in-step” with “key stakeholders”. This will “accelerate vaccine development and ensure access”, fortifying global health and improving equity.  

Professor Ruth Karron of Johns Hopkins University identifies in the profiles a “potential to catalyse vaccine development and activate new research collaborations”.  

“Our goal is to provide stakeholders, including R&D funders, policymakers, regulators, manufacturers, and the public, with the insights necessary to make informed defcisions and accelerate the development of vaccines that will have the greatest impact.”  

Some of our wonderful speakers have contributed to this project, so do let us know your thoughts on their work, and how you think these VVPs can inform your work, if at all. For more insights and updates, and to ensure you don’t miss our interview with Dr Tufet Bayona, make sure you subscribe here.

UK JCVI encourages routine vaccination: gonorrhoea and mpox

UK JCVI encourages routine vaccination: gonorrhoea and mpox

In November 2023 the UK’s Joint Committee on Vaccination and Immunisation issued advice to the government on a routine targeted vaccination programme for the prevention of gonorrhoea alongside advice on a routine vaccination programme against mpox for those at greatest risk. JCVI recommends that both programmes should be offered on an “opportunistic” basis through specialist sexual health services with experience in assessment and identification of people at increased risk of infection with bacterial STIs. The UKHSA and Department of Health and Social Care state that ministers will consider the advice before making policy decisions.  

Gonorrhoea 

The JCVI states that gonorrhoea is a bacterial STI caused by the Neisseria gonorrhoea bacterium and is the “second most commonly diagnosed” STI in England; around 80,000 cases are diagnosed a year. It is transmitted through unprotected anal, oral, or vaginal sex, or genital contact with an infected partner. People who are infected may not display symptoms but can still transmit infection.  

“Typical” symptoms include thick green or yellow discharge from the vagina or penis, and painful urination. The infection can also cause pelvic inflammatory disease, ectopic pregnancy and infertility, or painful infection in the testicles and prostate. 

“Gonorrhoea causes significant morbidity and remains a public health concern globally.” 

This concern increases as resistance to antibiotics increases; WHO considers the pathogen a priority pathogen due to the widespread antimicrobial resistance. In the UK, the recommended first-line therapy is ceftriaxone, to which resistance remains “very low”. However, resistance is increasing. 

The UK has been conducting surveillance for “over 100” years, and the number of diagnoses in 2022 was the “highest annual number on record”. These rates are “consistently disproportionately higher” in “specific communities”. These include: 

  • Those who live in the most deprived areas 
  • People of black Caribbean ethnicity  
  • People born in Central or South America (this measure is used as a proxy for being of Latino, Latina, or Latine ethnicity) 
  • Young people 15-24 years old and gay, bisexual, and other men who have sex with men (GBMSM) 
“Natural infection does not give protection against future infections, and among both GBMSM and heterosexuals, a recent history of gonorrhoea is a reliable predictor of future reinfection with gonorrhoea or other STIs.”  
JCVI’s recommendation 

The latest advice suggests that a targeted vaccination programme should use the 4CMenB vaccine to prevent gonorrhoea. It is a 4-component serogroup B meningococcal vaccine containing: 

  • 3 main Neisseria meningitidis proteins 
    • Neisseria heparin binding antigen (NHBA) 
    • Neisserial adhesion A (NadA) 
    • Factor H binding protein (fHbp) 
  • Meningococcal serogroup B outer membrane vesicles (OMVs) 

There is one licensed 4-component vaccine in the UK: Bexsero. This is manufactured by GSK and authorised for the prevention of meningococcal disease in patients over the age of 2 months. It’s used in the routine childhood programme administered at 8 weeks, 16 weeks, and 1 year for the prevention of meningococcal disease.  

“Neisseria meningitidis and Neisseria gonorrhoeae are closely genetically related with between 80 to 90% sequence homology. This homology gives the potential for cross-protection from OMV containing meningococcal B vaccines against Neisseria gonorrhoeae.”  

The JCVI agreed that the targeted programme should be “initiated” using the 4CMenB vaccine for gonorrhoea prevention in those who are “at greatest risk”. It emphasises that individuals who are offered vaccination must understand that real world studies have estimated that the vaccine has “between 32.7% to 42% effectiveness against gonorrhoea”. Therefore, although it would “be expected to reduce the chance of becoming infected”, it would “not completely eliminate the possibility”. 

“Vaccinated individuals could expect to have some reduction in their own risk of contracting gonorrhoea; however, the main benefit of a vaccination programme is expected to be at a community level.” 

Professor Andrew Pollard, Chair of the JCVI, hopes that the programme would not only “be a world first” but “should significantly help to reduce levels of gonorrhoea, which are currently at a record high”. Dr Katy Sinka, Head of Sexually Transmitted Infections at UKHSA, described a vaccination programme that would reduce gonorrhoea cases as a “hugely welcome intervention”. 

“We saw a rapid rise last year with more cases than ever before and with gonorrhoea becoming increasingly resistant to antibiotics, tackling this infection is a serious concern.” 
Mpox 

Mpox (previously called monkeypox) is a “rare disease caused by infection with the mpox virus”, an orthopox virus related to the viruses that cause smallpox and cowpox. JCVI states that before early 2022, cases of mpox in the UK were “either associated with travel to or from countries where mpox is endemic”. However, in May 2022 there was a “large outbreak” in the UK that presented a “different” pattern and scale to what had previously been observed.  

During this outbreak, cases were “primarily identified among gay, bisexual, and other men who have sex with men” (GBMSM) without a history of travel to endemic countries. From this it was inferred that there was community transmission; epidemiological surveillance suggested that this occurred from person-to-person contact in “defined sexual networks of GBMSM”.  

In response, although there was no licensed vaccine for protection against mpox, there was “good evidence” that the Modified Vaccinia Ankara – Bavarian Nordic (MVA-BN) provided cross-protection to mpox when given pre-exposure. The MHRA approved this vaccine for immunisation against mpox in September 2022. However, due to a limited supply of vaccines, intial recommendations focused on first doses.  

JCVI’s recommendation 

For mpox, the JCVI advises an “ongoing routine vaccination strategy” to prevent outbreaks and protect those at risk of exposure. This advice encourages the strategy to “target GBMSM who are at highest risk of exposure”; they will be identified via sexual health services through “markers of high-risk behaviour” such as those used to assess eligibility for HIV pre-exposure prophylaxis (PrEP). These criteria include: 

  • A recent history of multiple partners 
  • Participating in group sex 
  • Attending sex-on-premises venues 
  • A proxy marker such as a bacterial STI within the last year 

Furthermore, JCVI encourages efforts to “ensure” that the vaccine is “offered equitably to those at equivalent risk”, including “transgender women or gender-diverse people assigned male at birth”. Dr Sinka commented that “while mpox case numbers across England remain very low” the community should “not be complacent”. 

“Any routine vaccination offer to those at highest risk of infection will help ensure we remain on top of the disease and prevent any major future outbreaks.”  

Updates to the latest advice are expected as further information about “vaccine effectiveness and duration of protection” becomes available.  

How might these recommendations influence policy for better infection control in the UK, and can we expect to see other areas follow this decision? If your country has a better approach to infection management, why not share it? For more on vaccination policy and practice don’t forget to subscribe here.  

FDA approves Valneva’s world-first chikungunya vaccine

FDA approves Valneva’s world-first chikungunya vaccine

In November 2023 Valneva announced that the US FDA has approved its single-dose, live-attenuated vaccine for the prevention of disease caused by chikungunya virus: IXCHIQ. The vaccine has been approved for individuals aged 18 or above who are at “increased risk of exposure” to chikungunya (CHIKV). The approval was granted under accelerated approval based on anti-CHIKV neutralising antibody titers, and continued approval for the indication relies on confirmation of clinical benefit in confirmatory studies.  

What is CHIKV? 

Chikungunya is a mosquito-borne viral disease caused by chikungunya virus, a member of the Togaviridae family. It is transmitted by Aedes mosquitoes, endemic in parts of the Americas, parts of Africa, and Southeast Asia. Infection provokes symptomatic disease in up to 97% of humans after 4-7 days after a mosquito bite. These symptoms include acute onset of fever, debilitating pain, headaches, and nausea. 

“While mortality with CHIKV is low, morbidity is high.” 

The virus often causes “sudden” outbreaks with “high attack rates”, affecting between one-third and three-quarters of the population in areas where the virus is circulating. The economic effects are considered “significant”, and the medical and economic burden will grow as the primary mosquito vectors increase their geographic spread.  

“The global market for vaccines against chikungunya is estimated to exceed $500 million annually by 2032.” 

Until this approval there were no approved vaccines or effective treatments, allowing chikungunya to be a “major public health threat”.  

IXCHIQ 

In the US, IXCHIQ is a live-attenuated vaccine indicated for the prevention of disease caused by CHIKV in adults aged 18 and above who are “at increased risk of exposure”. It is administered as a single dose by intramuscular injection. Valneva reports that, with this approval, the vaccine becomes the “world’s first licensed chikungunya vaccine” to address the “unmet medical need”.  

Pivotal Phase III results were shared in The Lancet in June 2023, but the company will continue to evaluate antibody persistence for “at least five years”. The FDA states that it is “requiring” Valneva to conduct a post marketing study to “assess the serious risk” of “serve chikungunya-like adverse reactions” following administration of the vaccine.  

An ongoing clinical study in adolescents between the ages of 12 and 17 is continuing in Brazil. This forms part of an agreement between Instituto Butantan and Valneva in January 2021 to ensure the vaccine is “more accessible” to low- and middle-income countries (LMICs). This study is funded by CEPI and could support future regulatory submissions in the age group and licensure in Brazil, signifying the first potential approval for use in an endemic region.  

Valneva also expects this study to support regulatory approval in Europe; initial safety data was included in a submission to the EMA last month. The vaccine was granted PRIME designation by EMA in 2020. A regulatory review is also taking place in Canada.  

Who will benefit? 

Valneva suggests that the vaccine will “initially” address the “potential needs” of US travellers, fitting “seamlessly into Valneva’s global established travel vaccines business”. The company intends to begin commercialising IXCHIQ in the US at the start of 2024, while “continuing to support the work towards an anticipated vote” from the Advisory Committee on Immunisation Practices at the end of February. FDA’s Director of the Centre for Biologics Evaluation and Research, Dr Peter Marks, is hoping that “older adults and individuals with underlying health conditions” will benefit. 

“Today’s approval addresses an unmet medical need and is an important advancement in the prevention of a potentially debilitating disease with limited treatment options.”  

The approval is a source of pride for Valneva’s CEO Thomas Lingelbach, whom we interviewed at the Congress in Washington this April about “unmet medical needs”. He described it as an “important step forward” and “personally” expressed “a huge thank you” to everyone involved. Notably, he looks forward to the ongoing trial results. 

“I would also like to recognise CEPI and Instituto Butantan for their collaboration in potentially bringing this product to low- and middle-income countries.” 

CEPI’s CEO Dr Richard Hatchett is “proud” of his organisation’s contribution and offered his congratulations to “our partner Valneva” on “this historic achievement”. 

“The first-ever licensed chikungunya vaccine will play a crucial role in preventing the suffering caused by this debilitating disease.” 

He emphasised that the partnership with Valneva and Instituto Butantan, with “support from the EU”, will ensure the vaccine is accessible to the “people most affected by the virus”. Dr Juan Carlos Jaramillo, Chief Medical Officer at Valneva, echoed this intention. 

“Our objective is to make this vaccine available to the largest number of people that will benefit from it.” 

Dr Jaramillo reflects that “more than 75%” of the global population lives in “areas at risk” due to factors like “global warming and climate change”. Will Valneva’s vaccine reach these people in time? How do you think the FDA approval might drive further progress for other areas? 

For more insights into vaccine approvals don’t forget to subscribe to our weekly newsletters here.  

Childhood vaccine refusal study: what is to be done?

Childhood vaccine refusal study: what is to be done?

In a study published in BMC Medical Ethics in November 2023 the authors present a systematic review of normative arguments made about parental refusal of routine vaccination. Describing the topic as an “ethically contested area”, the researchers searched 9 databases for the period of January 1998 to March 2022. The goal of this publication is to offer “researchers, practitioners, and policymakers” a “synthesis of current normative literature”. In this article we examine the results and how it can support future research to “better understand the role of cultural context in normative judgements about vaccination” and “more comprehensively translate the nuance of ethical arguments into practice and policy”.  

Routine rejections 

The authors acknowledge that “vaccine rejection has existed for as long as vaccines”. Despite the “significant contribution” of childhood vaccination to a decrease in global child morbidity and mortality, some parents reject vaccines for their children. The reasons for this rejection “vary widely” and are often associated with “social setting”. A stated example is parents in high-income settings, among whom 2-3% reject routine childhood vaccines, where factors include previous “bad experiences”, concerns about safety, doubt about either the effectiveness or necessity of vaccines, preference for “alternative” health approaches, or “participation in particular social groups of communities”. 

“Vaccination plays a dual role in disease prevention: it serves to protect the vaccinated individual from disease, and when vaccination rates reach a high enough threshold for some diseases, also protects the broader community – including those who remain unvaccinated – by disrupting disease transmission through herd immunity.” 

This dual role “complicates ethical questions” about vaccine refusal. Health care providers, communities, and governments influence vaccine acceptance “by various means”. For example, interventions like incentives and recommendations or strategies like cost reduction may determine a parent’s decision. On the other hand, mandates can be imposed, and the study acknowledges that these are “not always well-supported”.  

Although there exists a “broad literature” on the ethics of childhood vaccine rejection, the authors claim that there is no systematic review of this literature. Therefore, they “sought to systematically explore and characterise” arguments about parental refusal of routine vaccination. This is intended to inform vaccine policy and practice.  

The review and results 

The survey identified 5,231 publications, of which 822 duplicates were removed; the remaining 4409 records were “screened by title and abstract”. After further eliminations, the resulting group included 117 journal articles, 3 theses, and 1 book. Journal articles included were from 3 main areas or a combination of them: medicine, philosophy or ethics, and law. The articles addressed “two central questions”: 

  1. Whether vaccine refusal was justified (to be known as ‘refusal’ arguments) 
  2. Whether various policy or practice responses to those who reject vaccines are justified (to be known as ‘response’ arguments) 

Most of the papers addressed the ‘response’ arguments (61%), with a small group addressing ‘refusal’ arguments, (19%) and about 18% considering both. Less than 2% had a “different focus”.  

‘Refusal’ arguments 
“On balance, most of the literature argues that it is not justifiable for parents to refuse routine vaccination for their children.” 

Most of the literature that falls into the ‘refusal’ category is based on three key areas of concern: 

  1. Respect for autonomy, the doctrine of informed consent, and the value of liberty 
  2. Consequences for the child and others 
  3. The normative significance of parental trust, distrust, and uncertainty 

These concerns are “not discrete” and “are often weighed against one another, linked by causal claims, or held in tension”.  

Respect for autonomy, the doctrine of informed consent, and the value of liberty 

15 papers from the sample present arguments that vaccine refusal is justified based on respect for parental autonomy, rights, or liberties. Some argue that refusal is justified as a preservation of legal rights or expression of religious freedom. Opposition arguments argue that “considerations regarding respect for autonomy are, or can be, outweighed by the potential harm caused to the child and others by not vaccinating”. These arguments include legal and religious perspectives.  

Consequences for the child and others 
“Most of the literature argues for or against the justifiability of vaccine refusal based on consequences.” 

These consequences include the potential harm from vaccine preventable diseases, or vaccines themselves, as well as the potential benefits from herd immunity. The authors note that herd immunity is “deployed in different ways”. Those who justify vaccine refusal in certain circumstances suggest that in settings with a “high level” of herd immunity, the risk presented by an unvaccinated child is not sufficient to override respect for parental autonomy, and that the benefits of “community protection” do not justify the “individual risk” posed by the vaccine. Furthermore, some argue that “some diseases are not harmful enough to proscribe vaccine refusal” and “vaccine injury contributes to and justifies refusal”.  

On the other hand, arguments that refusal is not justifiable consider the “duty” to contribute to herd immunity as a “public good” or the unfairness of “free riding” on that herd immunity. Additionally, the refusal of “a few” may “undermine herd immunity” and cause harm “to the many”; the greatest risk of this is borne by the most vulnerable. These arguments include those written by authors writing from religious perspectives.  

Another account from a vaccinating parent presents the idea that “harms resulting from non-vaccination” are “blameworthy”. They interpret these harms as an “intentional act of aggression against vaccinated children”. The notion of the “child’s interests” is “frequently” raised. Alongside concerns for the consequences of non-vaccination for the child come concerns for autonomy “in the broad sense of being able to direct one’s life in accordance with one’s values or aims”. 

The “interests of the child” are considered in a general sense as well as a legal sense; this term is used by the authors to imply “the formal ‘best interests of the child standard’”. The legal construction is used on both sides. 

The normative significance of parental trust, distrust, and uncertainty 

The sample included a set of papers written from the perspective of parents who chose not to vaccinate, with many of these contributions seeking to justify vaccine refusal; these justifications were often “grounded in distrust”.  

“They call into question vaccine safety and effectiveness, and the accuracy of the reporting of adverse events following immunisation. They claim financial conflicts, constructing clinicians, clinical medicine, and/or regulatory agencies as untrustworthy or non-credible.” 

Empirical studies of non-vaccinators are used to support parental preferences for “natural infection” over a vaccine. However, non-vaccinating parents were not alone in this line of argument; some authors referred to the “lack of absolute certainty” of vaccine safety, especially regarding newer vaccines. This argument “depicts vaccine proponents as driven by commercial interests”, which permits mistrust and refusal

“Contra this, one paper asserts that refusal on the grounds of mistrust of government or medicine is not justifiable, as it is inconsistent with the scientific evidence and the well-established regulatory processes in place.”  
‘Response’ arguments 

The literature examines four main responses to non-vaccination: 

  1. Government mandate policies and other coercive policies 
  2. Exemptions to mandate policies 
  3. Individual practitioner and medical practice responses 
  4. Withholding health resources 
“Much like the refusal arguments, some response arguments are absolute in their position, while others advocate weighing competing values in a context-specific way.” 
Respect for autonomy, the doctrine of informed consent, and the value of liberty 

Just as with the literature on refusal, many arguments about policy and practice responses to non-vaccinating parents “depend on the interrelated concepts of respect for autonomy, informed consent, and liberty”.  

A handful of papers engage with the issue of practitioners vaccinating against parents’ will, arguing that “forced vaccination by healthcare providers violates parents’ autonomy and/or the ethical requirement for informed consent”. Some authors offer alternatives to forced vaccination, such as rebuilding trust. However, proponents of forced vaccination use the harm principle and the ‘best interest of the child standard’ to justify their position. 

Another group of papers draw on autonomy or liberty justifications in comparison with harm or risk of harm considerations.  

“Arguments justifying mandates are often legal in nature and use, for example, the harm principle or case law to argue that the freedom or liberty to choose not to vaccinate is limited by the risk of ill health and/or death to the child or others.”  

One author suggests that legal actions should be brought against parents who “harm others by refusing vaccination”. The idea is that this would “discourage refusal” and “compensate victims” if claims are successful. Others argue that mandates are justifiable if the “exercise of liberty rights poses a threat to public health”.  

Some arguments that mandates are not justifiable rely on arguments about risk of harm, yet many make arguments from the perspective of autonomy, informed consent, and personal liberty. One author suggests that even if mandates improved vaccination rates, they “damage trust” and make refusers “more steadfast in their decision” so are unsustainable. A few authors present “middle-ground positions” that are “autonomy- or liberty-preserving” such as persuasion or weakly enforced mandates. Others argue that “policy responses should take the least coercive approach that is feasible and effective”. This argument seeks to “balance the needs of the individual with public health”.  

Authors who support conscientious objection to mandates argue that these provisions “contribute to the collective good of a culture of respect for autonomy” or “reflect the ‘American ideal’ of personal freedom”. On the other hand, those opposed to these provisions argue that challenges to mandates based in religious freedom have failed in case law.  

“Authors disagree about whether certain policies or practice responses do, or do not, respect autonomy or uphold important liberties.”  

The notion of “nudges” is considered “autonomy-preserving” with some weighing “multiple normative considerations”. However, some consider the “invasive nature of immunisation” a reason for increased need for “independent and informed decision making”.  

Consequences for the child and others 
“Many of the arguments in this literature consider individual and collective consequences…and propose that these may override other normative considerations.” 

The paper implies that “risk and prevention of harm is particularly pertinent”. Arguments about mandates often feature “concern about consequences” such as increased vaccination rates leading to fewer disease outbreaks and associated harms. Mandates are occasionally justified by the “duty to contribute to herd immunity”. This includes under the “clean hands principle”.  

Others argue that mandates are not necessary to achieve high levels of population immunity, from which “state coercion is unjustified”. Mandate opposition also includes arguments that vaccine safety is not absolute or that mandates are a “disutility”.  

“Consequences to the child and others are used to justify whether responses should be applied in general practice settings.” 

For example, one paper considers the consequences of treating non-vaccinating families for general practitioners, suggesting that practices that care for unvaccinated children should disclose this to other patients.  

A “small body of literature” examines the responsibility for the consequences of non-vaccination to make arguments about responses to non-vaccination. Examples include an article that “seeks to justify discriminating against unvaccinated children with a vaccine preventable disease by limiting their access to health resources”. This relies on precedents like surgery being denied to obese people or smokers. The implication is that “those who contribute to their own ill-health” are not deserving of healthcare.  

Inequity 
“Some critiques of policy or practice responses to non-vaccination emphasise that these responses can have inequitable effects and argue that this is unjustifiable.” 

In these cases, “exemption policies are a key focus” with some arguing against exemptions to mandates on the grounds that these “unevenly distribute the risks and benefits of vaccinations”. These authors claim that the “inaction of a few compromises the health of the most vulnerable” or “disenfranchises those with medical contraindications for vaccines”.Some authors who oppose coercive mandates or practice dismissal for non-vaccination critique these responses as having inequitable effects.  

The duty of practitioners and the state 

Several papers consider the duties of practitioners and duties of the state to respond to non-vaccination in “ways that go beyond simply weighing up consequences, implications for autonomy or freedom, or equity of impacts”.  

Duties for practitioners include protecting a child from their parent’s beliefs, if the beliefs are likely to cause harm, and protecting patients in the waiting room from risks posed by non-vaccinating patients. On the other hand, some authors consider a health professional’s obligation to provide healthcare in the best interest of the child despite the parent’s decision, which counters practice dismissal.  

Some assert that the state is “obliged” to discourage non-vaccination for reasons included a “fundamental duty” to protect society, a responsibility to “protect herd immunity as a common good or to reduce social and financial burdens and costs”. Some arguments focus on exemptions, proposing that states can’t justify such exemptions because the government’s interest in protecting society “outweighs the individual’s interest” or because “vaccination is a social and moral good owed by a society to its children”.  

So what? 

At the end of a lengthy review, which we have merely summarised above, the authors highlight an “opportunity for interdisciplinary collaboration” to “widen the scope and reach of normative arguments about non-vaccination”. Although arguments about the justifiability of non-vaccination and “what should be done about it” can “positively influence” routine vaccination rates, they can also “alienate non-vaccinating families” unless they are deployed “with their perspectives in mind”.  

If you’ve made it this far and still have the energy to engage with what you’ve read, do let us know your thoughts on the paper, which you can access in full here. We understand that the issues explored are contentious, so we are interested in thoughtful responses. In particular, if you work in vaccine uptake and deployment how might this inform your work? For more on research into vaccine attitudes and practices do subscribe to our weekly newsletter here.  

Vaccines for everyone: study investigates HPV strategies

Vaccines for everyone: study investigates HPV strategies

Research published in Cell Host & Microbe in November 2023 reaches a “somewhat provocative conclusion” that HPV vaccination is so effective that screening protocols might need a review. The paper suggests that “comprehensive human papillomavirus (HPV) vaccine implementation” is “essentially changing the ecological conditions of this virus-host interaction worldwide”. The researchers included over 60,000 women from 33 Finnish communities born between 1992 and 1994. They were divided randomly into groups based on their cities’ HPV vaccination strategies and followed up after vaccination to test for 16 types of genital HPV. 

HPV and vaccine strategies 

HPV is described by the CDC as the “most common STI”. Although common, we do have effective vaccines to prevent the diseases caused by HPV, which include some types of cancer. This vaccine is currently recommended for “everyone” up to the age of 26 in the US. In the UK the recommended group includes other people at “higher risk”.  Although we have this effective vaccine, the latest research aims to evaluate several different immunisation strategies and understand the effects of a successful strategy. 

What does the study find? 

The study evaluates the long-term, population level effect of “community-randomised gender-neutral and girls-only HPV vaccination” on the “ecology” of the remaining oncogenic HPVs among young adult women who were vaccinated in adolescence. The researchers identified a “significant depletion” of high-oncogenicity vaccine-targeted HPV types 16,18,31, and 45 in gender-neutral and girls-only vaccination communities at the 4-year follow up after vaccination. However, this was consistent 8 years after vaccination “only among gender-neutral vaccination communities”.  

Their “most important finding” is the “significantly increased” oncogenic HPVs ecological diversity from 4 to 8 years after vaccination “exclusively in gender-neutral vaccination communities”, despite the clearance of the vaccine-targeted types in these communities”. 

“This rising ecological diversity of the oncogenic HPVs in gender-neutral vaccination communities with a stronger herd immunity compared with girls-only vaccination communities is likely the first recorded sign of ecological niche occupation by the non-vaccine-targeted HPV post-population-level vaccination.”  

So, what does this all mean? Previous research has demonstrated the “need to opt for gender-neutral HPV vaccination strategies” to meet WHO-targeted eradication of the oncogenic HPVs. To do this, the authors claim that we must “understand the evolutionary dynamics of these oncoviruses”, particularly under “long-term vaccine-induced selective pressure”.  

“Taken together, understanding the differences in the transmissibility, antigenic variation, and oncogenic potential of the remaining HPV types in the newly established ecological niche following different vaccination strategies creates new basis for future cancer screening of HPV-vaccines and the herd effect protected non-HPV-vaccinated women and men.”  
Painting a picture 

Professor Ville Pimenoff, lead author, senior researcher at Karolinska Institutet, and professor at the University of Oulu, told STAT that it is “clear that there’s a stronger protection” achieved when you “have both genders vaccinated”. 

“This paper nicely paints a picture that indeed the vaccine is most efficient when you vaccinate boys and girls.”  

Professor Pimenoff highlights that “apart from the individual” protection, you also secure “herd protection”. The findings, he suggests, might indicate a need to rethink screening approaches. There is a cohort of women about to reach screening age in Finland who have been vaccinated. Different HPV varieties may be detected, leading to a “reasonable number of women” testing positive for types that are included in protocols but are “low risk”.  For these people, there is a chance of “overdiagnosis” or misdirection of public health resources. Therefore, Professor Pimenoff believes that screening could be limited to high-oncogenic types and conducted less frequently.

Others weigh in 

Professor Stephen Duffy of Queen Mary University of London is quoted by Science Media Centre, praising the “interesting and well conducted study”. However, he urges interpretive caution. 

“While we should not rush to change screening policy…it would be prudent to check if these results are replicated elsewhere, and to consider the implications for which populations we screen and how we screen them.” 

Professor Margaret Stanley of University of Cambridge warned that, despite the “high standard” of the analyses, we should not rush to change the HPV screening programme in the UK. 

“Evidence from national immunisation programmes with high coverage and good surveillance of HPV infection and disease pre- and post-vaccination is needed before re-evaluation of screening programmes and strategies.”  

How do you think this study could inform national screening? If you are interested in more insights into the latest vaccine research don’t forget to join our newsletter list here.  

BioCina and CPN Vaccines expand Gamma-PN partnership

BioCina and CPN Vaccines expand Gamma-PN partnership

In November 2023 BioCina and GPN Vaccines announced that they are expanding their partnership to develop GPN’s proprietary engineered whole-cell vaccine: Gamma-PN. This is a vaccine against Streptcoccus pneumoniae, a bacterium responsible for life-threatening infections. BioCina will manufacture “large-scale cGMP batches” for the programme.  

Streptococcus pneumoniae 

Streptococcus pneumoniae is responsible for up to 2 million deaths worldwide every year due to infections like pneumonia, bacteraemia, and meningitis. It is a Gram-positive “commensal organism” in the respiratory tract, which means that it can benefit from the human body without causing harm. Humans are the “only known host”. Although it is sensitive to penicillin, there is a growing rate of resistance. 

“This leaves vaccination as a critical tool in disease control.” 

GPN’s technology is based on a strain that “lacks capsular polysaccharide, is avirulent, and safe to handle”. It is inactivated with gamma irradiation to create the vaccine. This process offers an advantage over other methods as it “maintains the structures of conserved surface antigens” which allows effective induction of protective immunity”.  

The partnership 

BioCina has a facility in Australia with a “rich history” of working with recombinant proteins in microbial systems, such as E. coli. The company’s CEO, Mark W. Womack, is “extremely proud” of the opportunity to continue supporting production of the vaccine, which “has the potential to protect so many olives against a broad range of serotypes”.  

GPN Vaccines’ Chair and CEO Professor Tim Hirst is “delighted” to progress with the next stage of manufacture with BioCina as the “CDMO of choice”. 

“They successfully optimised the manufacture of Phase I material, and we now look forward to working with them to deliver a scaled-up process for the manufacture of Phase II material suitable for clinical evaluation worldwide.”  

For more updates on partnerships and vaccine technology don’t forget to subscribe to our weekly newsletters here.  

WHO shares Tuberculosis Report 2023: more effort needed

WHO shares Tuberculosis Report 2023: more effort needed

In November 2023 the WHO shared the Global Tuberculosis Report 2023, a “comprehensive and up-to-date assessment” on the epidemic and progress in preventing, diagnosing, and treating the disease at all levels. The report uses data from national ministries of health, with 192 countries and areas providing insights into more than 99% of the global population and cases. WHO reflects that the report “underscores a significant worldwide recovery” from 2022, an “encouraging trend” in response to the “detrimental effects of COVID-19 disruptions” on tuberculosis measures.   

The ‘what’ and ‘why’ 

The report begins with an introduction to this “preventable and usually curable disease”: tuberculosis (TB). It is caused by the bacillus Mycobacterium tuberculosis, spread through bacteria expelled into the air by infected patients. Despite the progress that has been made in prevention and control, WHO reports that, in 2022, TB was the “world’s second leading cause of death from a single infectious agent”, following COVID-19. It caused “almost twice as many deaths as HIV/AIDS”. 

“More than 10 million people continue to fall ill with TB every year.” 

 Roughly quarter of the global population is believed to have been infected with TB, and the risk of developing TB disease is highest in the first 2 years after infection. However, some may clear the infection. Although the disease “typically affects the lungs”, it can affect other areas as well. If a patient cannot access treatment, the risk of death is high, but for those who receive the recommended 4–6-month course of anti-TB drugs, there is an 85% chance of curing it.  

“Universal health coverage (UHC) is necessary to ensure that all people who need treatment for TB disease or infection can access these treatments.” 

The report also states that the number of people who become infected and develop disease, and consequently the number of TB-related deaths, can be reduced through “multisectoral action” to address determinants such as “poverty, undernourishment, HIV infection, smoking, and diabetes”. Despite these management strategies, WHO calls for “research breakthroughs” such as a new vaccine to “rapidly reduce” TB incidence. 

In September 2023, a high-level meeting on TB resulted in a political declaration that “reaffirms” global targets. This report, just over a month later, comprises 3 components. The main report presents “key findings and messages”, which we explore below. To access the report yourself, click here.   

Main findings and messages 

The report offers an optimistic indication that we have seen “major global recovery” in the number of diagnoses and patients treated after 2 years of “COVID-related disruptions”. Although this has “started to reverse or moderate” the effects of the pandemic on the number of people dying or experiencing illness with TB, the disease was still second to COVID-19 as the cause of death from a single infectious agent. While there is a positive trend, global targets set in 2018 “have been missed” and others remain “off track”.  

Case notifications 

The “most obvious and immediate” consequence of COVID-19 on TB was a “large global fall” in the number of people who were “newly diagnosed with TB and reported”. Between 2019 and 2020 there was a reduction of 18%, from 7.1 million to 5.8 million, with a “partial recovery” to 6.4 million in 2021. In 2022, 7.5 million people were newly diagnosed and officially notified as a TB case, a “rebound” to above the pre-COVID-19 level that “probably” reflects the diagnosis of a “sizeable backlog of people” as well as an increase in cases.  

Deaths caused 

The report infers from the reduction in reported cases that “the number of people with undiagnosed and untreated TB had grown”. This means that there was an increase in deaths from TB and more community transmission of infection, which later results in increased numbers of people developing TB. In 2022 the total number of deaths caused by TB was 1.30 million, which is down from “best estimates of 1.4 million in 2020 and 2021”. COVID-related disruptions are estimated to have resulted in “almost half a million excess deaths from TB” between 2020 and 2022, compared to the number if pre-pandemic trends had continued.  

Number of people developing TB 

In 2022 an estimated 10.6 million people became ill with TB, an increase from 10.3 million in 2021 and 10.0 million in 2020. The TB incidence rate (new cases per 100,000 population per year) is believed to have increased by 3.9% between 2020 and 2022. This comes after an average decline of about 2% a year from 2010 to 2020. The subsequent “reversal of progress” reflects the estimated effect of disruptions to essential services during the pandemic/  

Milestones 

This finding contrasts “some success stories” at regional level with a “mostly off track” warning. The first End TB Strategy milestones for reductions in TB disease burden were a 35% reduction in total deaths and a 20% reduction in TB incidence rate by 2020, in comparison with 2015. The second milestones were set for 2025: a 75% reduction in deaths and a 50% reduction in incidence. 

“The first milestones set for 2020 have not yet been reached either globally or in most WHO regions and countries, and the second milestones are far away in most parts of the world.” 
Beyond 2022 

The report refers to 26 country-specific models for the period of 2020-2022, which also allow projections for subsequent years. It is hoped that if the recoveries in 2022 are sustained, the global number of deaths should “continue to decline”. The upward trend in TB incidence may be reversed in 2023 or 2024.  

Global targets can only be achieved if diagnostic, treatment, and prevention services are offered “within the context of progress towards UHC” with “multisectoral action to address the broader determinants”. When countries adopt the Sustainable Development Goals (SDGs), they commit to achieving UHC by 2030. 

The need for a vaccine 

The End TB Strategy targets will not be met without “intensified research and innovation”. The priorities identified in the report include a “vaccine to reduce the risk of infection” and a vaccine or drug to “cut the risk of TB disease in people already infected”. In 2020 Member States adopted WHO’s strategy for research and innovation, which seeks to encourage “accelerated” research and innovation and “improve equitable access” to the results of this research.  

Despite some progress, research is “constrained by the overall level of investment”. Although WHO recognises “modest increases”, recent data show that only “half of the global target” from the first high-level meeting on TB has been secured.  

Dr Tedros Adhanom Ghebreyesus, WHO Director-General, commented that humanity has the “opportunity that no generation in the history of humanity has had: the opportunity to write the final chapter in the story of TB”.  

Have you read the report yet? Let us know your thoughts in the comments. For more on TB vaccine development at the World Vaccine Congress West Coast this month get your tickets here. If you can’t join us, don’t forget to subscribe for more insights.  

EU and Africa CDC share agreement on access and manufacture

EU and Africa CDC share agreement on access and manufacture

In October 2023 at the Global Gateway Forum, held in Brussels, the EU Commission signed €500 million for global health and an additional €134 million to increase local manufacturing and equitable access to quality, safe, effective, and affordable health products in Africa. An agreement was signed by Africa CDC’s Director-General, Dr Jean Kaseya, and European Commissioner for International Partnerships, Jutta Urpilainen to complement the Team Europe Initiative on Manufacturing and Access to Vaccines, Medicines, and Health Technologies (TEI MAV+) for Africa.  

Learning from COVID-19 

Africa currently imports 99% of the vaccines it requires. The consequences of this dependence on imported vaccines were highlighted during the COVID-19 pandemic. President of the European Commission, Ursula von der Leyen, reflected that a “key” lesson from the pandemic was that “vaccine and medicines sovereignty is key to defeating global health threats”.  

Therefore, the Commission is investing in programmes to empower the continent to strengthen local pharmaceutical manufacturing and improve access to health products.  

Funding 6 national plans 

6 African countries will receive funding within the €134 million package to support the “sustainable implementation” of their national plans: 

  • Egypt – €3 million 
  • Ghana – €32 million 
  • Nigeria – €18 million 
  • Rwanda – €40 million 
  • Senegal – €25 million 
  • South Africa – €16 million 

Africa CDC reports that these efforts “align with the shared development objectives and geopolitical priorities” of the European Union and African Union. This was emphasised by Jutta Urpilainen’s statement that the EU is “committed to strengthening health systems and securing global chains around the world”. Dr Jean Kaseya confirmed that the agreement “solidifies our shared vision” 

“This action-oriented partnership aims to advance the New Public Health order and expand local manufacturing in Africa.”  

For more on global vaccine manufacturing efforts and investments in global health, why not join us at the West Coast Congress this month? If you can’t make it do sign up to our newsletter here.  

MSD Animal Health pursues cattle health success

MSD Animal Health pursues cattle health success

In October 2023 MSD Animal Health announced that the European Medicines Agency Committee for Veterinary Medicinal Products (CVMP) has issued a “positive opinion” for BOVILIS CRYPTIUM. This vaccine is indicated for the “active immunisation of pregnant cows” to protect against Cryptosporidium parvum (C. parvum) infection. Later, in November, FarmingUK reported that MSD Animal Health has also launched a new bovine coronavirus vaccine.  

What is C. parvum?  

C. parvum is a “highly infectious” parasite that causes cryptosporidiosis. MSD Animal Health describes this as “one of the most significant gastrointestinal diseases in cattle”. Associate vice president of the global ruminant business at MSD Animal Health, Philippe Houffschmitt, commented that it is a “relentlessly challenging pathogen for cattle producers”.

“It is highly contagious and fast-spreading, and its contamination can be unavoidable in environments where cattle, goats, and sheep live.” 

Therefore, Mr Houffschmitt is “pleased” that the CVMP “recognises the vaccine’s capability” to support efforts against “such a significant problem”. The vaccine raises antibodies in colostrum against gp40, which can provide protection for calves at birth through vaccination of pregnant heifers and cows. Calves are “most vulnerable” at birth, and the parasite “plays a major role in the development of calf scour”.  

“Calf scour is the most common cause of disease and death in calves during the pre-weaning period.” 

Furthermore, it has longer term effects on weight gain.  

Bovine coronavirus 

Around the same time, the farming world highlighted the launch of a bovine coronavirus (BCoV) vaccine from MSD, offering potential relief to farmers from the plight of bovine respiratory disease (BRD). VetSurgeon suggests that this is “continually highlighted as a critical area for overuse of antibiotics”, emphasising a need for more effective prevention strategies.  

Addressing the British Cattle Veterinary Association in October, Paul Burr of Biobest Laboratories suggested that bovine coronavirus is the “most prevalent virus” identified in routine screening and samples from BRD outbreaks. Associated with both enteric and respiratory diseases in ruminants, BCoV is a cause of neonatal calf diarrhoea. 

Kat Baxter-Smith, MSD Animal Health veterinary advisor, commented that the availability of their latest vaccine offers “another tool” in the “armoury to improve control of this costly disease. FarmingUK states that this could alleviate the “high cost from an emotional and business productivity perspective”.  

Bovilis Nasalgen-C  

Where BCoV is implicated in a BRD problem, the vaccine can be administered to calves as a single 2ml intranasal dose. Immunity develops within 5 days of administration. VetSurgeon states that it can be stored for up to 24 hours at room temperature and is suitable for small and large herds as it is available in one, five, and 20 dose packs. 

For more insights into vaccines for animal health don’t forget to subscribe to our weekly newsletters here.  

Nasal COVID-19 vaccine shows promise in animals

Nasal COVID-19 vaccine shows promise in animals

Researchers from the University of Maryland shared in November 2023 that they have made progress in developing a nasal spray vaccine that delivers the SARS-CoV-2 spike protein to cells in the airway. Their research paper, published in Nature communications, reveals that in animal studies this has shown a significant reduction in infection and spread of COVID-19. The team believes that their technology has applications in other respiratory illnesses, such as influenza and RSV. 

Target the source 

The paper states that SARS-CoV-2 can be shed from asymptomatic infections and spreads “predominantly through droplets and airborne aerosols”. Because the virus “first enters the nose or mouth” and then replicates within the epithelial cells of the nasopharynx, prompting an upper respiratory infection, the nasal mucosa and nasopharynx are the “primary sites of exposure” to the disease before dissemination to other areas.  

Current intramuscular vaccines “can effectively prevent severe diseases and deaths”, but do not effectively “elicit protective mucosal immunity in the upper respiratory tract”. Therefore, “opportunistic breakthrough infections” are enabled in vaccinated individuals. Additionally, SARS-CoV-2 can “linger in the nasal mucosa” even after infection has been cleared. The authors suggest that evolutions to the virus necessitate a “safe and protective mucosal vaccine” to “block the viral entry and reduce or eliminate the viral spread”.  

The ideal solution would be nasal spray vaccines, which can “elicit local secretory IgA antibodies and resident T and B cell responses in the upper respiratory tract and the lungs”. Furthermore, they are less invasive, with potential to increase vaccine uptake. In their research, the Maryland team determined the ability of a protein called neonatal Fc receptor (FcRn) to deliver an intranasally-administered antigen and induce protective mucosal and systemic immunity to SARS-CoV-2 infection.  

Progress in animals 

The team administered their vaccine to mice before exposing them to ancient SARS-CoV-2, Delta, and Omicron variants of COVID-19. The mice that were exposed to the Delta variant died, while between 83% and 100% of vaccinated mice survived.  

Furthermore, although mice exposed to major Omicron variants survived, there was a significant reduction in inflammation and virus loads in vaccinated mice compared with unvaccinated mice. Another result that comparisons between nasal and injected vaccination revealed a more potent immune response in the airway and lungs for the nasal vaccine.  

The results indicate a positive future for FcRn-mediated respiratory immunisation. The study authors describe it as an “effective and safe” strategy to maximise the “efficacy of vaccinations against infection and transmission”. 

How do you think nasal spray vaccination could improve our efforts against SARS-CoV-2? Would you be more inclined to receive or administer this technology? 

For more on COVID-19 technologies why not join us for COVID-19 and beyond at the Congress in Santa Clara this month? If you can’t make it, don’t forget to subscribe here.  

4 vaccine hubs get funding: UK Vaccine Network

4 vaccine hubs get funding: UK Vaccine Network

In November 2023 the UK’s Minister for Health and Secondary Care, Will Quince, announced at the Association of Southeast Asian Nations (ASEAN) science, technology, and global health reception that “more than £30 million” will be invested in 4 new “vaccine manufacturing research hubs” across the UK Vaccine Network. The hubs are led by Imperial College London, University College London, the University of Oxford, and the University of Sheffield and will involve experts from “across Africa, Asia, and Latin America” according to the UKRI.  

“Together, they will use the lessons from the global rollout of COVID vaccines to improve the process of manufacture and distribution in LMICs.”  
Partnerships against pandemics 

Minister Quince is “proud” to build on partnerships between British universities and “global vaccine developments”. Included in the plans is the creation of a “dedicated UK-South-East Asia Vaccine manufacturing Hub”.  

“If another pandemic strikes, life-saving vaccines will be more readily available across south-east Asia and the world.”  

Furthermore, Minister Quince commented that the UK is “working closely” with “our friends in the Secretariat” to develop the ASEAN-UK Health Security Partnership. 

“This will bring the full force of our expertise to bear in tackling shared global health challenges.” 

The speech concluded with the reflection that these collaborations will “build the resilient and inclusive health systems” needed to “save lives across the world”.  

“Your Excellency, the measures we’re announcing today will help our countries tackle future pandemics, boost research into vaccines, and reduce deaths from infectious diseases.” 

UKRI states that the hubs have received a “share” of £33 million in UK aid funding from the Department of Health and Social Care, with a further £1.5 million from the Engineering and Physical Sciences Research Council.  

Who are the hubs? 
Imperial College London: Future manufacturing vaccine hub: accelerating the manufacture and deployment of cost-effective vaccines 

Led by Imperial’s Professor Robin Shattock, this hub draws on the expertise of three other UK universities, two UK institutes, and eight companies to “increase immunisation coverage” and improve outbreak responses through “rapid and cost-effective manufacturing and deployment”. Initial projects will take place in Vietnam, Bangladesh, and South Africa, before expansion to other countries.  

Imperial suggests that “effective distribution of vaccines” is “hampered” in rural regions of low- and middle-income nations by the “costs associated with their production and purification”, and cold storage requirements. Furthermore, an “additional challenge” is the demand for responses to “emerging threats” and AMR pathogens. To tackle these challenges the team will aim to “disrupt” vaccine production with “reliable technologies” that can be adopted “cost-effectively, at scale, and in compliance with regulatory requirements”.  

“They will create heat-stable vaccine formulations that minimise the need for low-temperature storage, and further develop four existing vaccine platforms, overcoming challenges including scalability, cost, and stability.”  

Professor Shattock is enthusiastic about the team’s ambition. 

“We are looking to exploit the next wave of biotechnology innovation to rapidly respond to emerging outbreaks and empower countries most at risk of infections to meet their local vaccine needs.”  
Imperial College London: Chanjo: catalysing the African vaccine manufacturing ecosystem 

This hub is led by Professor Faith Osier, and is an “African-led, academic-industry partnership” seeking to “catalyse the local ‘ecosystem’ necessary for establishing vaccine manufacturing in Kenya and Ghana”. Initial efforts will centre on an experimental malaria vaccine, comparing the “feasibility, scalability, cost-competitiveness, long-term economic viability, and social attitudes” across the mRNA and egg-based platforms. Both are relevant for both seasonal outbreaks and pandemic preparedness. 

Professor Osier commented that the need for local capacity is “urgent”, and she is “really excited” about the programme. 

“It leverages African scientists in the diaspora and on the continent, international collaborators, industry partners, business entrepreneurs, philanthropists, regulators, and policymakers.” 

The hub is also “female-led and gender-balanced” with a “transdisciplinary” team.  

“We draw on and enrich the UK’s expertise in vaccine bio-manufacturing, business entrepreneurship and innovation. By bringing together high- and low-income country partners for knowledge exchange and technology transfer, we can accelerate global access to vaccinations and treatments.” 
University College London and University of Oxford: Vaccines manufacturing hub for LMICs (Vax-Hub-Global)  

Led by Professor Martina Micheletti and Dr Catherine Green, this hub’s vision is to deliver flexible, easily transferable multi-product platforms and simplified engineering solutions to enable the development of low cost, effective, and globally deployable vaccines to LMICs. The Vax-Hub states that its “mission” is to place the UK at the centre of “integrated discovery through to bioprocess manufacture of next-generation vaccines”.  

The University of Sheffield: UK-south-east Asia-vaccine manufacturing research hub 

This hub is led by Professor Tuck Seng Wong and will establish a diversified, robust, sustainable, and equitable vaccine manufacturing ecosystem. The University states that the vaccines will target diseases like dengue, tuberculosis, and rabies, with a focus on protein, mRNA, and viral vector platforms. The hub is a consortium of four UK universities and eleven partners in South-East Asia and furthers an existing relationship between the University of Sheffield and Chulalongkorn University, Thailand.  

How do you think these hubs will establish secure and sustainable vaccine partnerships to promote more equitable access to vaccines in the future? For more on vaccine relationships don’t miss out on the Congress in Santa Clara this month. If you can’t make it, why not subscribe for more insights?  

CEPI and University of Oxford: vaccines against Junín virus

CEPI and University of Oxford: vaccines against Junín virus

In November 2023 CEPI and the University of Oxford announced a new project to “initiate the early development of prototype vaccines” against the Junín virus. This has been selected as an “exemplar” of the Arenavirus family, with the hope that the resources generated through the project can “give the world a head start” in the development of vaccines against Arenaviruses within 100 days of their identification.  

Junín virus 

Junín virus is the “causative agent” of Argentine Haemorrhagic Fever, with symptoms ranging from muscular pain and dizziness to rashes. It has a 15%-30% case fatality. CEPI describes it as “endemic to the Pampas of South America”, the fertile lowlands that span over a million square kilometres.  

The virus is a member of the Arenaviridae family, “generally spread by rodents”. The family was first identified with the discovery of Lymphocytic choriomeningitis virus (LCMV), isolated in 1933 during a study. Of the 15 arenaviruses that are known to infect animals, 5 cause disease in humans, including Junín virus. Lassa fever is also a member of the family, one of CEPI’s priority pathogens and on WHO’s R&D Blueprint list.  

Oxford’s vaccine efforts 

CEPI states that the team in Oxford was “able to develop a COVID-19 vaccine with unprecedented speed” partly thanks to their prior research into MERS, a “closely related virus” in the coronavirus family.  

“This gave the team a significant head start when COVID-19 emerged because they had solved many of the critical vaccinology problems for coronaviruses in advance.”  

In this project, CEPI and Oxford aim to “replicate this approach” for the Arenavirus family by “generating crucial knowledge about vaccine design and biological mechanisms linked to protection”. CEPI will provide up to $25 million for preclinical and Phase I clinical development using the ChAdOx platform, which was the foundation for the Oxford COVID-19 vaccine, and other rapid response platforms. 

Responding to a wakeup call 

Dr Richard Hatchett, CEPI’s CEO, reflected that COVID-19 was a “wake-up call to the world” and highlighted the “critical need to be better prepared for future viral threats”.  

“This new project will harness the University of Oxford’s extensive vaccinology experience and its innovative ChAdOx vaccine technology – one of only a handful of vaccine platforms proven to work at speed, scale, and low cost – to expand the world’ scientific knowledge on Arenavirus vaccines.” 

Dr Hatchett intends the project to generate “vital resources” for the “proposed Global Vaccine Library”. Oxford’s Professor Teresa Lambe commented that the project will unite scientists in Oxford and Latin America, working with “both viral vector and mRNA technology”.  

“Our work will not only inform best-in-class vaccines against the Junín virus, but it will also support vaccine development for the broader group…It is this wider impact that could crucially help the world develop and manufacture safe, affordable vaccines at speed.”  

For more technology and partnership updates don’t forget to subscribe to our weekly newsletter here.  

All for One Health: marking One Health Day 2023

All for One Health: marking One Health Day 2023

Friday 3rd November 2023 is the 8th annual One Health Day, observed internationally to “raise global awareness” of the importance of One Health “collaborations” and intentions. The day promotes understanding of the approach and seeks to encourage implementation. The UN Environment Programme suggests that the “theme” for this year is “Act Together for One Health”. How can you contribute to global efforts? In this article we will explore the approach and how it is being put into practice.  

What is One Health? 

WHO states that One Health is an “integrated, unifying approach” that seeks to “balance and optimise the health of people, animals, and the environment”. It recognises that these different aspects of ‘health’ are not as distinct as previously considered; the health of one depends on the health of others. Health thought leaders love the concept of ‘breaking out of siloes’ and this is a classic example of just that. The UN FAO explains how: 

“The One Health approach leverages the idea that problems impacting human health, animals, plants, and the environment can be effectively resolved through improved coordination, communication, and collaborative actions across disciplines and that these solutions be sustainable.”  
How is One Health practiced? 

We can first examine the One Health Joint Plan of Action, launched by the Quadripartite Secretariat for One Health in October 2022. The plan sought to “create a framework” to “integrate systems and capacity”. This is a 5-year plan with six “interdependent action tracks”.  

 

How is this plan being implemented and held accountable as it progresses? The following points are presented in the report: 

  • The One Health Joint Plan of Action (OH JPA) will be supported by an implementation framework with workplans at global, regional and country level. 
  • A joint process will be established to develop the implementation framework. 
  • The OH JPA aims to engage wider stakeholders on particular themes and activities and to help with advocacy and maintaining the urgency, public support, political momentum, and visibility of the One Health approach. 
  • The Quadripartite regional coordination mechanisms mirror the role of the global Secretariat at regional level. 
  • The Quadripartite will develop a monitoring and evaluation framework with targets and indicators.  
  • The targets of the OH JPA will be linked to reflect their contribution to attaining the relevant targets of the SDGs. 
  • Implementation at country level may be linked to UN Sustainable Development Framework implementation. 
  • A One Health toolkit will be developed. 

WHO indicates that the OH JPA implementation guide will be released later this year to support countries in their implementation of the approach. Furthermore, on One Health Day this year, WHO is hosting an event in the dialogue series, aiming to answer the following questions: 

  • What is the current status of the One Health implementation? What are the challenges, gaps, and opportunities? 
  • How is the technical and advocacy support of the Quadripartite helping countries to implement the OH approach? 
  • What are the planned next steps for translating the One Health approach into actions with the OH JPA? 
Community involvement 

How are you implementing the approach in your work? We’d love to hear your examples, particularly if you are doing something to observe One Health Day. Some of the experts we have spoken to in our Congress Conversations series at previous events have outlined how their work fits into the approach, or how it informs their efforts. We have provided a few examples below but encourage you to read around if you are interested! 

Dr Alex Dehgan: “Planetary health meets public health: Dr Alex Dehgan 

Dr Jennifer McQuiston: “Driving public health conversations: Dr Jennifer McQuiston 

Dr Jomana Musmar: “Breaking One Health barriers with Dr Jomana Musmar 

Joel Harris: “Agricultural equilibrium: old meets new with Joel Harris 

We also look forward to sharing more conversations over the coming weeks, so do make sure you have subscribed to our newsletter and stay tuned!

Study sheds light on vaccine-related blood clotting

Study sheds light on vaccine-related blood clotting

Researchers from the University of Birmingham shared in October 2023 that a paper in Blood identifies how blood clots associated with Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT) occur. Building on previous studies that have highlighted that patients with VITT produce antibodies that bind to Platelet factor 4 (PF4), the team used blood donated by healthy participants and serum and plasma from patients with VITT to understand the role of PF4.  

Understanding PF4 

Platelet factor 4 (PF4), known also as C-X-C motif ligand 4 (CXCL4) is a 7.8 kDa chemokine released from platelet α-granules. It forms “tetramers with a compact globalar structure” and a “strong equatorial positive charge”. Furthermore, it binds strongly to negatively charged molecules such as endothelial proteoglycans and “infectious agents”.  

Although antibodies to PF4 “underlie the pathogenesis” of both heparin-induced thrombocytopenia (HIT) and VITT, the “direct effect of PF4 on platelets has not been extensively studied”. In the recent study, the authors demonstrate that PF4 binds the thrombopoietin (TPO) receptor, c-MPL, causing activation of Janus kinase 2 (JAK2).  

A confident future 

Dr Phillip (Pip) Nicolson suggests that the “major advances” in vaccine development prompted by the COVID-19 pandemic were “thrown into sharp relief” after the identification of “rare cases” of VITT.  

“While there were alternative vaccines available to continue to provide protection against the coronavirus in some countries around the world, understanding the mechanisms behind these cases are critical to ensuring that the technology for delivering vaccines can be used with confidence in the future.”  

Dr Richard Buka commented that the team not only identified a “new way” the platelets are being activated but have paved the way for “new drugs to protect against blood clots”. The research indicated that ruxolitinib, a treatment for some types of blood cancer, can block the receptor being triggered by PF4. However, in its current form it is “unsuitable for use in VITT patients”. Despite this, the identification of this pathway demonstrates a “potential future way to protect patients”.  

Dr Samantha Montague stated that it is “gratifying” to have identified a “new, important biological mechanism through trying to thoroughly understand a new disease”. 

“This work helps us to understand more fundamental things about how blood clots form and may also be relevant in other related diseases.”  

Funded by the British Heart Foundation, the team will continue to explore how patients at risk of VITT can be identified to improve vaccine deployment. 

“Future vaccine programmes around the world can be delivered while understanding and managing the potential risk for those few at greatest risk.”  

For more vaccine insights at the World Vaccine Congress West Coast get your tickets here, and don’t forget to subscribe.