The clinical trial of an experimental universal influenza vaccine developed by NIAID researchers from the Vaccine Research Centre has started to enrol volunteers. The Phase I trial will test that safety and immunogenicity of the vaccine in a healthy adult population. As we explored last year, experts have set their sights on a universal flu breakthrough in the next few years. Could this vaccine be the one?
The vaccine in trial
The vaccine, known as H1ss-3928 mRNA-LNP, will be tested for its safety and ability to induce an immune response in volunteers at Duke University, North Carolina. The trial is expected to enrol up to 50 volunteers, between the ages of 18 and 49. Following an initial dose evaluation with three groups, more participants will be enrolled to receive the optimum dosage. The study will compare results with recipients of a current quadrivalent seasonal influenza vaccine.
Unlike a previous vaccine, also developed by the Vaccine Research Centre, the H1ss-3928 mRNA-LNP vaccine uses an mRNA platform. The hope is that using a range of platforms to create a vaccine will offer greater potential for the discovery of a safe and effective candidate.
The study is conducted through the Collaborative Influenza Vaccine Innovation Centres (CIVICs) programme, created by NIAID in 2019. However, this is the first investigational universal flu vaccine candidate to be tested by the programme. It was manufactured at the Duke Human Vaccine Institute (DHVI).
Why is this important?
As estimated by the CDC, up to 52,000 people die of flu in the US every year. Despite the availability of seasonal flu vaccines, they are not immunogenic against every strain, instead focusing on an anticipated handful of strains. NIH reports that the problems associated with predicting could be avoided with a universal flu vaccine.
“An effective universal flu vaccine could eliminate these problems by protecting its recipients against a wide variety of strains and ideally providing durable long-term immunity, so people would not need to be vaccinated every year.”
The Acting Director of NIAID, Dr Hugh Auchincloss, believes that success would be a “major public health achievement”.
“A universal flu vaccine could serve as an important line of defence against the spread of a future flu pandemic.”
Next up in our series of Congress interviews is our conversation with Professor Petro Terblanche, CEO of Afrigen. She joined us at the Congress for a plenary session global manufacturing capability. We were delighted to secure some of her time to discuss the inequalities that became clear during the COVID-19 pandemic, and how we can improve access for future threats. We hope you enjoy the interview!
Introducing Professor Terblanche
Professor Terblanche is the CEO of Afrigen, a biotechnology company based in Cape Town. They host the mRNA hub programme, which we posted about recently here. Afrigen’s focus is on development and distribution of key biologicals to address unmet needs, particularly in low- and middle-income countries.
Lessons from COVID-19
For many of our speakers the COVID-19 pandemic was an educative experience, to say the least. However, Professor Terblanche brings a specific perspective on the question of the inequalities that were highlighted in the global immunisation efforts. She recognises the “landmark” achievement by many stakeholders to bring vaccines to the world, but suggests that in early and middle stages of the vaccination programmes there were “no vaccines for low- and middle-income countries”. Due to “vaccine hoarding” and the link between access and manufacturing, many countries were excluded from the global response.
To address the lessons from the pandemic and ensure “health security”, multiple initiatives were established to address the issue of “centralised vaccine manufacturing” and to promote a “decentralised” model for the future.
Building on the pandemic momentum
Although the pandemic highlighted some terrible inequalities, we also witnessed a unique opportunity to unite and innovate as a global community. We asked Professor Terblanche to tell us more about the positive side of this urgency.
“It was profound.”
Professor Terblanche suggests that we saw “unprecedented efforts” towards new platforms, new adjuvants, and new administration opportunities. This “profound” innovation was not limited to vaccines, but also diagnostic and therapeutic spaces.
“The pandemic did leverage, and unleash, a different energy.”
Furthermore, it brought the importance of vaccines to a “household level”, thanks to the “quest to be safe”.
“Vaccines became the household name.”
Although Professor Terblanche highlights the long journey ahead against vaccine hesitancy, she believes we have made great strides forward in vaccine education.
Afrigen and the importance of a workforce
Our next question for Professor Terblanche digs a little deeper into the work that Afrigen is doing, and with whom. She tells us that from the beginning, Afrigen’s “fundamental mandate” has been to “localise the manufacturing of vaccines for Africa”. Thus, when COVID-19 happened and WHO put out the call for applications to become hubs for technology development, “we were well suited”.
“We are very technology driven, very science and technology driven.”
At that time, Afrigen developed the technology and started sharing and training, transferring knowledge to 15 companies who were part of the network. Professor Terblanche proudly tells us that in the last 14 months they have trained 100 people in specific skills, from molecular biology to GMP cleaning. These efforts align with wider goals across the continent, such as Africa CDC’s workforce nurturing.
“Vaccines are not easy; they require a deep, technical knowledge base.”
As we observe the establishment of new facilities and the development of existing capabilities, we are curious to hear how sustainability factors in to what Professor Terblanche is doing. Her response is emphatic.
“Sustainability is paramount.”
The mRNA hub was created as a “response” to the pandemic; it will be a “fatal mistake”, Professor Terblanche warns, to not design the response to become “pandemic preparedness”.
“Pandemic preparedness requires sustainability.”
Although the programme is mRNA focused, there are challenges. For example we need a “pipeline of products”. We need to “reduce the cost of goods” through innovation, says Professor Terblanche. Furthermore, we “have to address the cold chain issues”, because the current requirements are not suitable for LMICs. Professor Terblanche emphasises the technology component in sustainability, stating that “building a platform for one product is not sustainable”.
Next, we need to ensure that we have an “ecosystem” that supports sustainable practices. From Professor Terblanche’s perspective, Afrigen’s ambition must be applied in different ways for different purposes. She compares the 15 participants of the network, with current capabilities ranging from mature and supported environments, to an incompletely developed ecosystem, to the final “green fields” group.
“The first group will hit the ground running, but we need to feed them with pipeline. The second group will take a little bit longer, and then there’s a third group that will take much much longer.
Whatever the application, Professor Terblanche is insistent that the response must result in pandemic preparedness.
An issue that is specific to Professor Terblanche’s experience of African development is local manufacturing procurement. She says the continent needs “major policy reform” to do “preferential procurement of locally produced vaccines”. Additionally, external support from organisations like Gavi and CEPI is essential.
“I am grateful to share that in the discussions we have with Gavi, with CEPI, with UNICEF, with The Global Fund, there is a clear realisation that procurement of local goods is essential for pandemic preparedness and for a sustainable vaccine industry.”
Discussion and partnerships at WVC
Our final question, as always, invites our speakers to share their hopes for the Congress, and what they are most looking forward to. For Professor Terblanche, the network opportunities are exciting. Afrigen’s meetings have a strong sustainability focus. They are proud that the programme has enabled Africa to collaborate with world leaders, biotechs, universities, and institutions across the globe.
“We are no longer just waiting for the world to innovate for us; we are able to innovate with the world.”
This final statement is an exciting hint at the emerging potential for innovation in Africa. We can’t wait to see what comes from Afrigen and partners, and are so grateful that Professor Terblanche had time to share her insights with us. For more like this, make sure you subscribe to our weekly newsletter. For more on the Congress this month, click here to download our post-Congress report.
Our next interview is with Dr Jay Berzofsky, Chief of the Vaccine Branch at NCI’s Centre for Cancer Research. He joined us at the Congress to participate in the Cancer and Immunotherapy Vaccines track, during which he explored triple synergistic combination immunotherapy. We are so grateful for Dr Berzofsky’s time and insights into cancer vaccine development and the challenges that come with it. We hope you enjoy the interview!
Introducing Dr Berzofsky
Dr Berzofsky kindly explains a bit about how his role works within the programme.
“We are government employees…we have nothing to do with grants for universities and so forth, but we do our own research.”
The branch is the vaccine branch, and they work on “basic science” and its applications to vaccines for HIV, cancer, and viruses that cause cancer, as well as COVID-19.
Triple synergistic combination immunotherapy
Dr Berzofsky kindly gave us a preview of his session the following day, which was to explore triple synergistic combination immunotherapy. He began by explaining that “there are different reasons why certain cancers may not respond well to immunotherapy”. He introduces “hot tumours”, those that are “inflamed” with T cells that “could kill the tumour cells”. However, the “tumour microenvironment” is “very immunosuppressive” and “prevents them from doing their job”.
“The T cells are there, but they need to be enabled.”
Next, Dr Berzofsky discusses “cold tumours”. These have no T cells infiltrating, often because the tumour doesn’t induce a good immune response. Essentially, the “immune system doesn’t see it as foreign”. These two different kinds of tumours need different strategies, suggests Dr Berzofsky.
“In the case of a hot tumour, you want to block the immunosuppression, to allow the T cells that are there to work.”
This is the case for melanoma, lung cancer, and a “number of other cancers”.
“In cold tumours, you need to generate an immune response, and that’s where the vaccine can come in.”
Inducing a T cell response that the “tumour itself failed to induce” converts the tumour from a cold tumour to a hot tumour. The vaccine, and the blockers of “negative regulation” such as checkpoint inhibitors, are synergistic!
“The vaccine can induce the T cells, but they won’t work if you don’t block the immunosuppressive environment.”
Clearly developing therapeutic cancer vaccines is a challenging task. When we asked Dr Berzofsky about this, he reckoned that “there are a number of challenges!” A major challenge that he does discuss is the need to encourage the immune system to “reject” the cancer as it might a transplant. The immune system can be “exquisitely specific”, unlike an external approach like chemotherapy; it can “distinguish very cleanly” what is foreign in the body.
“But remember, the cancer cells are not foreign organisms like bacteria or viruses that are completely different from your own cells – they arose from your own cells.”
The target therefore, is a vaccine that can “train the immune system to see those unique differences”.
Another challenge that Dr Berzofsky identifies is that there are “many immunosuppressive mechanisms” beyond checkpoints.
“One has this panoply of suppressive mechanisms to overcome.”
We don’t have “really good ways” of overcoming these in humans yet, so Dr Berzofsky calls for research to “more effectively illuminate these other suppressive mechanisms”.
“It may be a daunting task to try to block 8 or 10 different suppressive mechanisms at the same time…so we need to find common nodes of intersection where some of these suppressive mechanisms interact, so we can block more than one at the same time.”
What more can be done?
As Dr Berzofsky has suggested, more work can be done, as always! We asked about potential areas for development that he can identify. Following from his previous answer, he emphasises the importance of finding “better ways, that are safe, to eliminate these immunoregulatory cells”. However, we also have to “strike the right balance”; they are there for a reason.
“It’s just going to take more research.”
Although we can make progress in animals, Dr Berzofsky suggests that the next step is “human clinical trials”.
Coming to the Congress
When we asked Dr Berzofsky about why he was joining us, he commented on the quality of his colleagues’ presentations!
“Hearing all the wonderful speakers that come to this meeting every year!”
Apart from the opportunity to learn, Dr Berzofsky was looking forward to meeting and developing potential collaborations.
“One of the things that’s important in science as in so many fields, is networking, because none of us can do everything in our own small laboratory.”
We are so grateful to Dr Berzofsky for his time and insights into some of the most challenging vaccine endeavours of our time. We hope to continue this conversation at future events. For more like this, make sure you subscribe to our weekly newsletters.
At the World Vaccine Congress last month we were lucky to meet Dr Nora Disis of the University of Washington (UW), an expert in oncology. We are delighted that she made time to discuss combination therapies, the role of vaccines in cancer treatment, and the significance of access in her work. We are grateful to Dr Disis for her time and hope that you enjoy this interview.
Introducing Dr Disis
Dr Disis kindly outlined her current role for us. She joined us at the Congress to discuss combination immunoprevention and immunotherapy strategies.
We asked Dr Disis to tell us a bit more about the areas she was in Washington to discuss. She explained that, for cancer, the “antigens or immunogens are more weakly immunogenic” than other proteins.
“You’re kind of battling generating a robust immune response with a tumour that continues to grow.”
Therefore, “another strategy” that can slow the tumour’s growth or “hold the tumour at bay”, without compromising a vaccine’s efforts, “just makes sense”. In therapeutics, Dr Disis has seen that combination approaches “really potentiated the effect of both”. This is also true in prevention, where chemo-prevention agents can “help stimulate the immune response and make the vaccines more effective”.
What role do vaccines play?
To put it simply, Dr Disis thinks vaccines are going to be “very critical” for making immunotherapy drugs “more effective”. She suggests that “most patients” with common solid tumours do not have “highly mutated tumours”. This means that they are “not filled with T cells waiting to be unleashed”.
“I think that’s where vaccines may provide the key component.”
Dr Disis believes if you can immunise patients, get T cells “trafficking to tumour”, and “increase that tumour infiltrating lymphocyte load”, it makes sense!
“You’ll have a certain body of T cells that would be able to become activated and hopefully attack the tumour.”
Clinical trials and patient populations
With lots of discussion about clinical trials at the Congress, we asked Dr Disis what she thinks about improving the process to optimise outcomes. She suggests that “we’ve really struggled to figure out what should be the patient population that we immunise”. A conventional focus on “tumours that were rapidly growing” and “resistant to all chemotherapy” is now understood to be the equivalent of “trying to immunise someone who’s got an overwhelming infection”. In that context, vaccines are not particularly effective.
However, in the adjuvant setting, vaccinating fully treated patients with “no evidence of disease” but an “extremely high risk of relapse”, we are starting to see the “success of vaccines”.
“It’s taken us quite a long time to get to the point where we’re beginning to understand the specific patient populations that would be ideal for vaccination.”
What about access?
Following on from Dr Disis’ comments about patient populations we asked her a bit about access. Cancer treatments are renowned for being costly, so how can this be addressed? Dr Disis acknowledges that it’s “very hard in oncology” with some treatments being beyond reach for many. However, vaccines might offer a solution.
“Vaccines are the great levelling field.”
For her colleagues, she has advice on making vaccines.
“Do not make them complicated!”
She encourages people to think about things like transport potential when creating their vaccines. In fact, she believes that we have technologies that can be “widely applicable to a great number of vaccines and can be made very cheaply”.
“I would put out a call to my field; that should be one of the first things on their mind: “am I making this a therapy that is only going to be for people who have the money to afford it?”
Hopefully, with people like Dr Disis leading the charge, real change can be made in the field to ensure that therapies are available to more patients across the world. We are so grateful to Dr Disis for her time and look forward to hearing more at future events.
Make sure you subscribe to get more interviews sent to your inbox and check out the post-event report here.
Just days after the COVID-19 pandemic was declared no longer a public health emergency of international concern (PHEIC), mpox has followed suit. Cases of mpox, formerly monkeypox, have declined since the previous meeting of the IHR Emergency Committee. Despite this positive declaration, the Committee acknowledges “remaining uncertainties about the disease”, relating to “modes of transmission”, “poor quality of some reported data”, and “continued lack of effective countermeasures in the African countries” where mpox “occurs regularly”.
Updates on the situation
The Director-General, Dr Tedros Adhanom Ghebreyesus, commented on the sustained decline of cases across the world. He noted that almost 90% fewer cases have been reported over 3 months compared to the previous 3 months. However, the virus is still transmitting in certain communities.
At the meeting, representatives of Japan, Nigeria, and the UK provided updates on the situation within their countries. The Secretariat offered a “comprehensive update” on the epidemiological situation and response efforts, with a further update from the WHO Region of Africa. The Region reported that the majority of the 1500+ confirmed cases since January 2022 have been in Nigeria and the Democratic Republic of the Congo.
“There was little information on modes of transmission and the quality of reported data through surveillance systems was uneven in the African Region.”
The current global risk is described as “moderate” across much of the globe.
Although progress has been made through a global effort, the Committee recognised “remaining concerns”, which include duration of immunity after infection or vaccination, “insufficient evidence about vaccine effectiveness”, and “poor quality of data and inconsistency in reporting of cases”.
Despite concerns about the potential effects of large social gatherings among “high-risk groups” it was noted that many gatherings took place last year without a spoke in case numbers. Furthermore, some regions have post-emergency plans and have started to integrate the response into sexually transmissible infection programmes.
In Africa there are “concerns” about the situation, particularly concerning “recurring zoonotic transmission”. Wider concerns were raised about lack of access to vaccines, medicines, and diagnostic testing in many LMICS.
“Not all countries are receiving the support they need or have structures or systems to response to mpox, including inadequate support for marginalised groups.”
Moving to a long-term strategy
Although the Committee acknowledges the “uncertainties” surrounding mpox, it encourages a transition to a “long-term strategy” instead of the emergency measures demanded in a PHEIC. WHO states that the Committee “emphasised the necessity for long-term partnerships” to “mobilise” the necessary support for “sustaining surveillance, control measures and research for the long-term elimination of human-to-human transmission”, and “mitigation of zoonotic transmissions”.
“Integration of mpox prevention, preparedness, and response within national surveillance and control programmes, including for HIV and other sexually transmissible infections, was reiterated as an important element of this longer-term transition.”
The Committee noted that progress has been made “largely in the absence of outside funding support”. Furthermore, “longer-term control and elimination” will be unattainable without such support.
Just as with the COVID-19 change last week, the WHO Director-General issued Temporary Recommendations relating to the outbreak. These are intended to meet the objectives to “interrupt human-to-human transmission, protect the vulnerable, and minimise zoonotic transmission”.
“In implementing these Temporary Recommendations, States Parties should ensure full respect for the dignity, human rights, and fundamental freedoms of persons.”
Sustain and promote key elements of the mpox response strategy and review experience to inform public health policies, programmes, and actions.
Develop and implement integrated mpox control plans and an elimination strategy with the aim of preventing and stopping human-to-human transmission and/or mitigating zoonotic transmissions.
Maintain epidemiological surveillance of mpox, making every effort to ensure laboratory confirmation of suspected cases and reporting to WHO of confirmed cases and probable cases.
Report immediately all confirmed travel-related mpox cases to WHO.
Integrate mpox detection, prevention, care, and research with existing and innovative HIV and sexually transmitted disease prevention and control programmes, and other health services as appropriate.
Sustain and invest in risk communication and community support and engagement for affected communities and at-risk groups, including through health authorities and civil society.
Continue to implement interventions to avoid stigma and discrimination against any individuals or group that may be affected by mpox.
Support and enhance access to diagnostics, vaccines, and therapeutics to advance global health equity, in particular for most affected communities worldwide, including gay, bisexual, and other men who have sex with men, with special attention to those most marginalised within those groups, and in resource-constrained countries where mpox is endemic.
Continue to strengthen diagnositc capacity, decentralised access to testing and genomic sequencing, including sharing of genetic sequence data through public databases.
Continue to make vaccines available for primary preventative (pre-exposure) and post-exposure vaccination for persons and communities at high risk of mpox.
Ensure provision of optimal clinical care with infection prevention and control measures in place for suspected or confirmed mpox in all clinical settings. Ensure training of health care providers accordingly.
Strengthen capacity in resource-limited and rural settings where mpox continues to occur, to better understand modes of transmission, quantify resource needs, and respond to outbreaks and sustained chains of transmission.
Implement a coordinated research agenda to generate and promptly disseminate evidence for key scientific, social, clinical, and public health aspects of mpox prevention and control. Continue clinical trials of medical countermeasures, including vaccines, therapeutics, and diagnostics, in different populations, in addition to monitoring of vaccine safety, effectiveness, and duration of protection from infection and vaccination.
Countries in West, Central, and East Africa, where mpox is endemic should make additional efforts to elucidate mpox-related risk, vulnerability, and impact, and to investigate, understand, and control mpox in their respective settings, including the consideration of zoonotic, sexual, and other modes of transmission in different demographic groups.
An article in Nature in May 2023 presents work from a collaboration between Genentech, Memorial Sloan Kettering Cancer Centre (MSKCC), and BioNTech. Dr Vinod P. Balachandran, surgeon-scientist at MSKCC has been working on pancreatic ductal adenocarcinoma (PDAC) for years in the hope of replicating the rare survival of some patients for others. Through a personalised RNA neoantigen approach, he may have finally found a route.
The article reports that PDAC is the “third leading cause of cancer death” in the US, and the seventh worldwide. Unfortunately, the survival rate of 12% has “remained largely stagnant for nearly 60 years” as incidence continues to grow.
“PDAC is projected to cause even greater global cancer deaths by 2025.”
Currently the only curative treatment is surgery, yet up to 90% of patients have disease recurrence at around 7-9 months and the 5-year survival is 8-10%.
“Radiation, biologics, and targeted therapies are also ineffective.”
Furthermore, PDACs are “almost completely insensitive to immune checkpoint inhibitors”. This is “partly attributed to the fact that PDACs have a low mutation rate”. They therefore generate few neoantigens, which mark the cancer as foreign to T cells. However, recent studies have shown that PDACs “harbour more neoantigens than previously predicted”, and studies of long-term survivors have suggested that “neoantigens may stimulate T cells in PDAC”.
Replicating survival traits
The authors state that, based on the observation that long-term survivors “mount spontaneous T cell responses” against “tumour-specific neoantigens not shared among patients”, they decided to investigate if “adjuvant individualised vaccines can stimulate neoantigen-specific T cells and provide clinical benefit”.
The known benefits of mRNA vaccine technology led the researchers to suggest that an effective mRNA vaccine could induce neoantigen-specific T cells in PDAC, eliminate micrometastases, and delay recurrence. To explore this, they conducted an investigator-initiated, Phase I clinical trial of sequential adjuvant atezolizumab (Genentech), autogene cevumeran restricted neoantigens in lipoplex nanoparticoles intravenously delivered, individualised NeoAntigen-Specific Therapy (iNeST), and mFOLFIRINOX in patients with surgically resectable PDAC.
A positive start
The study demonstrates that adjuvant autogene cevumeran, the individualised neoantigen vaccine based on uridine mRNA-lipoplex nanoparticles, in combination with atezolizumab and mFOLFIRINOX, is “safe, feasible, and generates substantial neoantigen-specific T cells in 50% of unselected patients with resectable PDAC”.
“Here, we provided evidence that despite the low mutation rate of PDAC, a mRNA vaccine can induce T cell activity against neoantigens in this cancer.”
The individualised mRNA cancer vaccines were tested in the adjuvant setting due to observations that vaccines against pathogens have “historically been most effective in preventative and not therapeutic settings”. From this the authors infer that “vaccine efficacy requires an optimally functioning host immune system”. However, in patients with advanced cancer, neoantigen vaccination is challenged by “global impairments in host immunity” and “knowledge gaps on neoantigen heterogeneity between tumours”. Therefore, the researchers recommend that vaccines are tested in patients with minimal residual disease.
Moving forward through challenges
The article shows that PDAC tumours do harbour neoantigens suitable for vaccines, and T cell can be generated in response to mRNA vaccines. Additionally, there is a correlation between vaccine-induced T cells and delayed cancer recurrence.
Although the trial was conceived in 2017, and began in December 2019, it encountered an enormous and familiar obstacle a few months in. Dr Balachandran told GEN that this “posed several unique challenges” such as “shutdowns and global supply chain disruptions”. Furthermore, the distraction presented by BioNTech’s task of manufacturing vaccines “to save the world” was another barrier to success. However, Dr Balachandran believes that intead of slowing the trial down, they were able to “accelerate it to complete it a full year ahead of schedule”.
‘We think this can hopefully speak to the idea that rapid custom cancer vaccination is feasible in the clinic.”
Dr Ira Mellman of Genentech admits that at the start, many people viewed the project as an “over-the-horizon or blue-sky thing”, with little expectation of success.
“Now, from two different sources that are totally independent, both using mRNA vaccines, they seem to have some rather significant glimmers of clinical benefit. Whether it’s the next big thing, I’m not prepared to say, but it could be.”
For more insights into therapeutic vaccine development, head to our therapeutic section to view previous articles.
In this interview we meet Mei Mei Hu, CEO and Co-Founder of Vaxxinity. She joined us at the Congress to explore the ideas of using vaccines to tackle chronic diseases and what supply and access lessons we have learnt. We were thrilled to catch up with her about her vision for “putting the tech in biotech” and democratising health. We hope you enjoy the interview!
Tell us about Vaxxinity
Mei Mei kindly gave us a bit of background to Vaxxinity, which is only 2 years old. Formed as a union between United Neuroscience and COVAXX, the team is now a “vaccine-dedicated company for any pandemic or epidemic that comes up”. As CEO, Mei Mei believes it is her job to ensure that everyone has what they need to do their job better.
Challenges for vaccine development
With all vaccines there are unique challenges associated with developing and deploying them. The team at Vaxxinity are tackling chronic diseases, which is “not a new concept”. However, it is a challenging one, Mei Mei says.
“Our body is very smart, so it doesn’t like to attack itself.”
Overcoming “immune tolerance” is key to encouraging the body to produce antibodies against the endogenous proteins associated with chronic diseases.
Effects of the pandemic
Many of the experts we spoke to have experienced some changes in their work due to the COVID-19 pandemic. For Mei Mei and her team, “early learnings” were accelerated.
“It also just highlighted our vision and brought a lot more focus on vaccines.”
Previously, vaccines existed in a poorly understood “blue ocean”, but thanks to the role they played in the pandemic, “everyone and their family knows what a vaccine is”.
Leading the field
As a young and energised team, Vaxxinity is hoping to “put the tech in biotech”. We asked Mei Mei what it is like to invigorate the vaccine community with innovation, and how she intends to stay ahead of the pack.
“One thing I love about tech is that they dream big.”
Biotech also “goes after really innovative technologies” but the mission is slightly different. Vaxxinity’s doing this too, but the overall purpose is “how can we democratise health”. In terms of leading the field, Mei Mei acknowledges that her team is using “breakthrough technologies”, but also trying to “reimagine” them.
“Can you reimagine a vaccine that can prevent chronic diseases as well? So, wouldn’t that be awesome?”
Access at the centre
Much of what was discussed at the event this year explored the importance of access, sustainability, or both. A vaccine is only useful when effectively deployed. Therefore, we asked Mei Mei how she and her team think about this.
“Access, and sustainability, they are the core of why we do what we do.”
Mei Mei recognises that monoclonal antibodies for chronic disease exist, which is “great for the most part”. However, they are “expensive”, “burdensome”, and “limited in how many people they can serve”.
“Access is our total mission, and that’s why we’re using vaccine technology.’
Why WVC Washington?
It’s always great to understand why our vaccine specialists join us at the event, and Mei Mei kindly shared her intentions for the few days.
“I think there’s a lot of challenging to the conventional thinking out there, and what better place to do it than at the World Vaccine Congress.”
Thank you so much to Mei Mei for her time and insights at what is always a busy event! We look forward to sharing more interviews over the next few weeks, so do make sure that you have subscribed to our weekly newsletter.
At last month’s Congress we were lucky to meet Dr Andrew Allen, CEO and Co-Founder of Gritstone bio, for a conversation about cancer vaccines and immunotherapy targets. He joined us at the event for the Cancer and Immunotherapy Vaccines track, and we were glad to sit down with him for more insights into his work and the work of the field. We hope you enjoy the interview!
As Dr Allen mentions, he is the CEO and Co-Founder of Gritstone bio, a publicly-traded company based in the US. Their facilities are on both the East and West Coasts. Gritstone describes a commitment to “progressing the field of immunotherapy”, which meant that Dr Allen was in a good position to chair the track!
One of Dr Allen’s sessions was on neoantigen immunotherapy for solid tumours, so we asked him to share a bit about what this involves. He suggests that this is an “idea that has been around for about 7 or 8 years”. Data published in 2014 indicated that “mutations in genes created altered proteins that could function as antigens for the immune system”. Thus, the neoantigen.
“The achilles heel of cancer seems to be that when those proteins change they can provide targets for the immune system.”
For Dr Allen, there is then an “arms race” between “a cell that’s trying to turn into a tumour cell, proliferating without restraint”, and the host’s adaptive immune response, “trying to identify foreignness, and eliminate it”.
“We’re trying to essentially tilt the battlefield in our favour by driving strong immune responses against those tumour neoantigens.”
Luckily, some pretty “elegant biology” works with us here. The mutations are only found in the tumour and are “foreign to your immune system”. Although this sometimes happens naturally, without attracting attention, T cells can “often” enter the tumour but “something stops them from completely eliminating the tumour”. However, most solid tumours don’t have lots of pre-existing T cells. Therefore, we need to “take a step back” and “generate the T cells”.
“We use vaccines to generate those T cells.”
Vaccines on the scene
Dr Allen mentions that vaccines are used to generate T cells. We asked what a successful cancer vaccine might look like, or what the ultimate goal for vaccine developers might be. For solid tumours, the “goal is to prolong survival”. Explaining the role of “biomarkers” or “surrogate markers”, Dr Allen suggests that the “goal” is to “impact those biomarkers in a very striking fashion”. This often happens in patients with advanced disease, before the platform can be moved backwards into an “earlier stage population”. In this population, the immune response is “better” and the tumour presence lesser, so there is greater opportunity to make a demonstrable difference.
The question of clinical trials
Some of the conversations that took place at the Congress were centred on the issue of improving clinical trials to produce better outcomes. We asked Dr Allen what his views on this issue are. For him, it’s a “really interesting area”. He suggests that in oncology, “we’ve been using the same endpoints for about 20 years now”.
“You’re looking for lesions to get smaller, and if they don’t get smaller, you say ‘that therapy doesn’t work’.”
However, this isn’t appropriate for immunotherapy, in which the goal is T cell proliferation within the lesions. When the T cells enter lesions, they can often get bigger, misinterpreted as “progression of disease – that’s failure”. What might actually be happening is proliferation of T cells causing a temporary enlargement, before the T cells “go to work” and the tumour shrinks. “Pseudo-progession”, says Dr Allen, is a “recognised problem” particularly for melanoma.
With vaccines, for cold tumours, the tumour has no T cell population until vaccination, where the notion of lesion expansion is once again “important”. Additionally, there is “good evidence” that some tumours that are responding to therapy develop mini lymph nodes! Lymph nodes are “fixed structures that are stable over time; they occupy space”.
“The expectation that the tumour has to go away for there to be a good outcome I think is based on these flawed ideas from the past.”
With these concerns in mind, Dr Allen suggests that radiology is “struggling” to “meet our needs of being a predictive biomarker”. His question, then, is “do we have something better”, to which he believes we can answer positively! The answer is “circulating tumour DNA”, which can be measured in the blood.
“You treat a patient and if their CTDNA goes down, they are likely to do well.”
This is a well-established approach, but the field has not yet made the transition.
“I think we’re going to find that CTDNA actually is a much better surrogate for overall survival, with immunotherapy.”
What was happening at the Congress?
We asked Dr Allen about his interests at the event, and he shared what he was most looking forward to. Apart from presentations from BioNTech and Moderna, Gritstone’s “competitors in the space”, there were opportunities to meet with other players in the field.
“It’s going to be an exciting year and I’m looking forward to just chatting about that with all of the experts here at this conference.”
We are grateful to Dr Allen for his time and his useful insights into technical details and wider field ambitions. We look forward to more from Gritstone bio at future events! For more interviews with experts in the cancer space, click here to subscribe. To see a breakdown of the event, click here for the post-event report.
Captain Dr Jennifer McQuiston joined us at the Congress last month to discuss the importance of animal vaccines and diseases that start at animal level. As Acting Director for the Division of High Consequence Pathogens and Pathology in the CDC, her insights are particularly useful! We were glad to meet her during the event for a conversation about her perspective on One Health and preventing diseases in humans through animal care. We are grateful to Dr McQuiston for her time, and hope that you enjoy the interview!
Introducing Dr McQuiston
Dr McQuiston’s role, like many of her colleagues’, is quite a mouthful, but she kindly set out her full title for us below! Her experience ranges from mpox to COVID-19, and her background as a veterinarian has proved useful to these challenges.
Why animal vaccines?
We know that animal vaccines have the potential to reduce animal morbidity and mortality, but what about the human effects? For Dr McQuiston, this area needs greater emphasis.
“The use of animal vaccines to protect public health or human health is an area that we really need to give a lot more discussion to.”
The “tantalising” possibility is that for zoonotic diseases we have “different intervention pathways” that we don’t have in purely human diseases. Many of the “same technologies” are involved, but sometimes the regulatory and approval pathways are “shorter and more direct”.
“I think that exploring, and in some ways exploiting those, to make sure that we can prevent diseases in animals, to me is the more viable pathway.”
The link that Dr McQuiston draws between animal and human health sounds very much like a One Health connection, so we asked about what this means to her. She suggests that “something like 75% of emerging diseases in humans start in animals”. This “hammers home” the importance of studying animals and their environments to understand the “transmission dynamic”.
“To me a One Health approach means that you’re bringing together veterinarians, and physicians, and manufacturers of animal vaccines and human vaccines, and you’re talking and having a dialogue.”
Through this dialogue, Dr McQuiston believes we equip ourselves to “drive human prevention” by looking at prevention in animals.
Collaboration is key
It may sound like a cliché, but collaboration is a recurring theme in our interviews, with many of our experts emphasising the importance of bringing together a diverse community to learn from each other. We asked Dr McQuiston about how her experience reflects this. She explains that this is her first World Vaccine Congress (we certainly hope it won’t be her last!) and how she sees a “real need” to unite people who are “part of public health problems” to collectively discuss solutions.
“If I can drive the conversation to how do we prevent the outbreaks from happening, my job end up being a lot easier! I think that collaboration, that conversation, is so important.”
With the confusion and contention around the origins of the COVID-19 pandemic, we asked how important it is to understand where a disease has come from. Dr McQuiston thinks it’s “very important” to do this research, and to involve scientists from different disciplines to play to their strengths. She refers to the mpox outbreak as a “tremendous example” of the need to identify reservoirs of zoonotic diseases.
Dr McQuiston calls for continued work in this area, particularly after her experience working on mpox reservoir identification.
“Once you know the species that’s responsible you can start to have conversations about how people protect themselves.”
Coming to the Congress
When we asked Dr McQuiston about her reasons for coming, she shared that her experience collaborating on a paper that “brought together people from a lot of different disciplines and areas” introduced her to Dr Cyril Gay. He led a panel that Dr McQuiston joined at the Congress. She was excited to meet people and discuss “really common passions” , so we hope this was fruitful!
Thank you to Dr McQuiston for her time and enthusiastic contributions to the conversation. We hope she will join us for future events!
After the “termination and suspension” of a grant awarded in 2019, NIH and EcoHealth Alliance have announced a grant from NIAID to conduct research into zoonotic coronaviruses. With the intention of addressing “salient questions” on the “origin, diversity, capacity to cause illness, and risk of spillover of these viruses to people”, EcoHealth Alliance will collaborate with the Duke-National University of Singapore Medical School.
Early in the COVID-19 pandemic, then-President of the US, Donald Trump, called for the cancellation of the grant in April 2020. Science suggests that this was due to “unsupported allegations” of a lab leak at Wuhan Institute of Virology.
“The project later drew concerns for experiments, conducted in virologist Shi Zhengli’s lab at WIV, in which researchers attached the spike protein of various wild bat coronaviruses to a different virus “backbone” in order to gauge the wild pathogens’ potential to infect human airway cells.”
This research would enable scientists to isolate the role of the spike protein and investigate coronaviruses that can’t easily be cultured. However, “critics” argued that this was “gain-of-function” (GOF) research. This argument was refuted by NIAID and Dr Anthony Fauci, its director at the time.
What do we know?
Ecohealth Alliance states that zoonotic coronaviruses (CoVs) “represent a significant threat to global health, as we have seen through the emergence of SARS-CoV, MERS-CoV, and SARS-CoV-2. Having identified bats as the wildlife reservoirs of SARSr-CoV, EcoHealth Alliance has published “hundreds” of novel sequences from wildlife in China and Southeast Asia.
“Our work has demonstrated that bats in this region harbour an extraordinary diversity of SARS-CoVs.”
However, the remaining questions are many, so this renewal grant is important in the eyes of its recipients.
Characterise and analyse more than 300 new whole genomes and large genome segments of SARSr-CoVs from archived samples to determine the processes underlying coronavirus recombination and identify viral strains with a high predicted risk of spillover.
Analyse archived samples from community- and clinic-based syndromic surveillance of people to identify evidence spillover, assess behavioural risk factors, and pinpoint evidence of illness.
Conduct in vitro viral chcaracterisation and in silico analysis of epidemiological data to identify hotspots of further CoV spillover risk.
Specific aims have been “revised” through consultation with NIAID and NIH staff to “respond to any ongoing concerns”. This has been achieved through the removal of “all on-the-ground work in China and all recombinant virus culture or infection experiments” as well as “additional oversight mechanisms”.
Identifying high-spillover risk bat SARSrCoV sequences in southern China and assessing drivers of recombination
Conducting community- and clinic-based surveillance of archived pre-COVID-19 human samples to identify SARSr-CoV spillover events, routes of exposure, and potential public health consequences
Characterising SARSr-CoV binding, ability to evade therapeutics/vaccines, and identifying spillover hotspots.
Are you satisfied that these aims address the original concerns, or would you prefer to see a more cautious approach?
In 2018, Integrum Scientific was formed by “global innovators” in response to “the need to address the deficiencies” and “broaden the benefits” observed in the international Ebola response of 2014-2016. Integrum is preparing for future threats and reducing their effects in the most vulnerable regions of the world.
“Integrum is dedicated to improving the effectiveness of clinical research and promoting prevention, preparation, and awareness.”
Here at VaccineNation we were lucky to meet the Integrum team in Washington last month. We spoke to CEO Joseph Sgherza, along with colleagues Dr Julius Lutwama, Brigadier-General Professor Foday Sahr, and Dr John Dye about the work they are doing. We are so grateful that the team made time to speak to us and we hope that you enjoy their perspectives!
We heard from CEO Joe Sgherza about his vision for Integrum. He explains that it is a “readiness response company” with an infectious disease board comprising experts from around the globe. Many of them were involved in response activities during the Ebola crisis of 2014. They now act as “sentinels” across the world in their personal capacities.
“Ensuring that we can make a difference, and help the greater good of research.”
What does a response look like?
Joe kindly explains the importance of uniting “stakeholders and players” in a global crisis. He emphasises the role of “in country experts” and “communicating effectively”, which is what he hopes Integrum achieves. As we hear from Dr Dye later, Integrum focuses on working with local experts in a disease outbreak to understand their needs.
The importance of communication
We asked Joe about how Integrum maintains this close relationship with local experts during crises, and how we can better encourage their inclusion during global health threat responses.
“In one word, it’s communication.”
Joe states that the “take home message” is asking key stakeholders “how can we be effective right now”, a message repeated by Dr Dye below. Furthermore, it is “more important than ever” to offer services where there are “gaps” by communicating with everyone involved.
“Not where you think you can fit in, but where you actually can make a difference in helping their situation.”
Putting this into practice
It’s one thing to have good intentions when coming to support a community in crisis, but it’s another to effectively implement these intentions. We asked Joe to explain how this works at Integrum. He presented the example of the Sudan and Marburg outbreaks, during which Integrum worked with Dr Lutwama to set up a research board with representatives from different “acumens”. It was led by Dr Lutwama “in country” to enable the team to “ask questions”, be “available immediately”, and to “disseminate the information of what’s happening real time”.
“We’re able to actually find out what the numbers are, what do they need, and then how does that impact the current clinical research we’re doing there?”
Coming to the Congress
What, then, is Integrum looking to gain from the Congress? Joe suggested that “more collaboration” was on the cards. Demonstrating to colleagues the “value” that the team can add was a key focus for the event.
“Being a small organisation, we are very nimble, and we’re able to get into places to assist.”
Joe describes Integrum’s ability to support with a “scientific need for convalescent plasma or for serum collection”. With current collaborations including work with CEPI and USAMRIID, the potential to “add value” continues to grow.
Next, we spoke to the other members of the team on site, so keep reading to hear from Dr Julius Latwama, Professor Foday Sahr, and Dr John Dye!
Introducing Dr Julius Lutwama
Dr Lutwama is the Head of Department of Arbovirology, Emerging, and Reemerging Infectious Diseases and Deputy Director of the Uganda Virus Research Institute. His specialisation is in surveillance for a range of infectious diseases.
“My department is the one that normally announces, or comes up with, all of these new diseases that are announced in the country.”
This is a huge responsibility on a national and international scale; Uganda is known to have “very many diseases”, according to Dr Lutwama, who encounters lots of these in his daily routine. Some of our community will remember that it was UVRI who released a statement in September 2022 about the Ebola outbreak.
The burden of disease in Uganda
As Dr Lutwama has already explained, Uganda has “very many diseases”. He tells us that “almost 40 diseases” have been identified for the first time in the country. This is partly because of the “many mosquitoes” and “many ticks”. Diseases circulating in Uganda include Zika and Chikungunya.
“Uganda is a hotspot for diseases.”
The importance of surveillance
Dr Lutwama’s role is centred on surveillance. We asked him about the importance of this in the context of disease, specifically in Uganda.
“It is very, very important.”
With so many diseases, often occurring in “rural areas”, people will suffer morbidity and mortality. In particular, surveillance helps to identify diseases before they spread “over a wide area” and become more widely noticed.
“When you do surveillance, you can get these diseases very quickly before they affect many people.”
Furthermore, the tragic reality of these diseases is that we rarely have approved vaccines. Therefore surveillance enables experts like Dr Lutwama to find them “as quickly as possible” and reduce the number of deaths from disease.
Introducing Professor Sahr
Professor Sahr is the Vice-Chancellor at the University of Sierra Leone, but also serves as Brigadier-General in the Republic of Sierra Leone Armed Forces Joint Medical Unit. In this role he assists the Ministry of Health and Sanitation with looking after the health of the country. During outbreaks in particular this support is critical.
Outbreaks in Sierra Leone
As Professor Sahr’s experience is deeply rooted in outbreak responses in Sierra Leon, we asked how prepared the country is for future threats. He indicates that from Ebola “some structures were established”; the government invested in structures such as supply chain and laboratories.Therefore, when COVID-19 emerged as a threat to the country, the response was “faster” because there was “some baseline”.
“That doesn’t mean that we are out of the woods.”
As always, there is “still room for improvement”. Within his role in the armed forces, Professor Sahr is encouraging training and developing clinical guidelines with the Ministry of Health and Sanitation.
Emerging diseases in Africa
Professor Sahr described the potential for “improvement” so we asked him to outline some of the threats that Sierra Leone is facing in the future. He suggested that the situation “does not stop” at Sierra Leone: “it goes across”. He shares with us his experience with “diseases that we thought are non-existent”.
“To me, when Ebola struck, it was not really a surprise.”
Thanks to the growing surveillance capabilities in his area, Professor Sahr suggests that emerging and reemerging diseases become less of a shock, allowing for a more appropriate response.
How does Integrum help?
Up next in our whistle-stop tour of the team is Dr John Dye, Viral Immunology branch chief in the US Army Medical Research Institute of Infectious Diseases. He kindly outlined some of the work that is being done in countries like Uganda and Sierra Leone, with the help of his colleagues. He tells us that the team collects samples from survivors of outbreaks.
“The idea is that we can look at their immune system, and how it has changed over time, to help us develop better vaccines for the future.”
A global ecosystem
Clearly, the work that the Integrum team is doing is critical. However, it can be hard to draw attention to this, particularly when the diseases that they are investigating are often contained in one region. We asked Dr Dye about keeping interest and investment high. As he acknowledges, many of the diseases are like “flash fires”: “they come up, and then they quickly retract”.
“It has been very difficult, but I think the world is starting to learn that we are all one ecosystem.”
With increasing globalisation, “the world is one backyard”. For Dr Dye, this means we need to “worry about everyone”. As this mindset spreads internationally, so does an understanding of the importance of Integrum’s work. Therefore, it is easier to secure funding and convince people to consider everyone in our “global ecosystem”.
How does Integrum promote fair access?
Although it’s important to increase global awareness and investment in areas where these diseases are rife, it’s imperative that when treatments or vaccines are developed, they are made accessible. Dr Dye explains that “anything” that the team develops is shared because the investigators in each country are “co-investigators”.
“They have intellectual property.”
When we asked Dr Dye what he was looking forward to at the Congress, his answer was simply “being able to moderate a session with two incredible African leaders”. He was excited to hear their experience and their own versions of “what they really need for outbreak response”.
“Not what we tell them they need, but actually what they need.”
We are so grateful for the time and energy that the Integrum gave us. It is fantastic to hear from an organisation so invested in learning from the communities it supports, and adapting to suit their needs. We hope to continue these conversations at future events. To stay updated as we release more interviews, make sure you have subscribed to our weekly newsletter.
A study in Pediatrics in May 2023 explores the effects of different messaging angles on parents’ intentions to vaccinate their children against COVID-19. Although no longer classified as a PHEIC by WHO, COVID-19 continues to cause global problems, particularly to vulnerable populations. The authors suggest that “persistent vaccine hesitancy” is believed to be “particularly pronounced among parents”, thus “hampering” efforts to control the pandemic
“Although vaccination of adults, adolescents, and children is ongoing, vaccinating children will be key.”
Among the obstacles to this effort, previous research has suggested that “fewer than one-half of parents are likely to vaccinate their children” against the disease. Understanding how to persuade more parents to vaccinate their children, therefore, is “imperative”. In the population-based survey, the researchers test the effectiveness of different types of messaging. The approach is useful because it enables the assessment of a “large population of interest” whilst “randomly assigning respondents to conditions”. It has been used for vaccination intention research in the past as well as other studies of parental intentions related of other areas of child health.
Through the Voices of Child Health in Chicago (VOCHIC) Paret Panel Survey, data were collected. Parent inclusion was based on being over 18 years old and living in Chicago, as well as being the parent of guardian of at least 1 child aged up to 17. The survey was conducted in English and Spanish, either online or by telephone, between October and November 2021.
Parents who answered that they had at least 1 child who was not yet vaccinated were randomly assigned to read 1 of 4 distinct messages about the COVID-19 vaccines. The study tested message types that are described as “familiar from paediatric and public health approaches”:
The COVID-19 vaccine is well-tolerate by children, with few side effects
The COVID-19 vaccine is safe and tested
Trusted parents are vaccinating their children against COVID-19
A control condition that provided information about the anticipated timeline for authorisation of vaccine in children
Following this message, parents were asked “how likely are you to get your child(ren) vaccinated against COVID-19?”. Response options were “very likely”, “somewhat likely”, and “not likely”. Surveys were completed by 1142 parents who reported on 1977 children. The research in question is based on responses from 898 parents about 1453 children who had not yet been vaccinated.
What does the study find?
“Overall, parents’ intentions to vaccinate children were higher if a parent received the trusted parents message compared with a control condition.”
For a more detailed breakdown of the results, click here to view the study. The authors call for future research to evaluate the messages to determine the “precise change” in vaccination intentions. They also acknowledge that as the parents in the sample are from a “major US city”, attitudes may differ to those who reside in “suburban or rural settings”.
The study indicates that the most effective messages to encourage parents to vaccinate their children against COVID-19 were centred on “other trusted parents” deciding to do the same. Messages that addressed the safety and testing history “may also be effective”. The researchers acknowledge that the findings may not be applicable in a “clinical context”, where it “may not be feasible for clinicians” to refer to trusted parents.
“Given the continuing pandemic and the centrality of effective vaccination among children in controlling future waves of COVID-19 illness at the population level, such messages may be some of the most important communications that paediatricians are currently providing.”
If you are a parent or guardian, what would encourage you to vaccinate your child against COVID-19, and what message would be ineffective?
At the fifteenth meeting of the International Health Regulations (IHR) Emergency Committee regarding the COVID-19 pandemic, held on 4th May 2023, the Committee members advised the WHO Director General that the pandemic is no longer a public health emergency of international concern (PHEIC). Acknowledging decreasing deaths and hospitalisations, as well as higher levels of population immunity, the Committee advised a transition to “long-term management” of the pandemic. Director General Dr Tedros Adhanom Ghebreyesus “concurs” with this advice.
“With great hope I declare COVID-19 over as a global health emergency.”
High levels of immunity
Although the global risk assessment is still considered “high”, the Committee recognised evidence of a reduction to this risk driven “mainly by high population-level immunity”. Through infection, vaccination, or both, this immunity combines with “consistent virulence” of circulation variants and “improved clinical case management”.
WHO provided updates on the status of global vaccination. The Committee was informed that across the world 13.3 billion doses of COVID-19 vaccines have been administered. Although 89% of health workers and 82% of adults over the age of 60 have completed the “primary series”, coverage in these groups is variable.
Deliberating the status of the PHEIC
The Committee reportedly considered the three criteria of a PHEIC. These are:
Whether COVID-19 continues to constitute an extraordinary event
If it continues to constitute a public health risk to other states through the international spread
Whether it potentially requires a coordinated international response.
“Although SARS-CoV-2 has been and will continue circulating widely and evolving, it is no longer an unusual or unexpected event.”
The Committee also celebrated the global enhancement of “functional capacities”, suggesting that the world has made “significant and impressive global progress” since the initial declaration of the PHEIC in January 2020. Although the PHEIC has been a “valuable instrument” to the global response, the Committee elected that “the time is right” to progress towards “long-term management”.
“Reaching the point where COVID-19 can be considered as no longer constituting a PHEIC should be seen as accolade to international coordination and commitment to global health.”
The Director General issued the following temporary recommendations to Member States. For more details visit the WHO website.
Sustain the national capacity gains and prepare for future events.
Integrate COVID-19 vaccination into life course vaccination programmes.
Bring together information from diverse respiratory pathogen surveillance data sources to allow for a comprehensive situational awareness.
Prepare for medical countermeasures to be authorised within national regulatory frameworks to ensure long-term availability and supply.
Continue to work with communities and leaders to achieve strong, resilient, and inclusive risk communications and community engagement (RCCE) and infodemic management programmes.
Continue to life COVID-19 international travel related health measures.
Continue to support research.
Do you agree that now is the right time to move to “long -term management”, or would you prefer the WHO took a more cautious approach?
In an article published in NEJM in May 2023 experts from the Division of Vector-Borne Diseases presented a call to “revisit the need for human West Nile virus (WNV) vaccines”. WHO suggests that, although 80% of infected patients do not show symptoms, the virus can cause a fatal neurological disease in humans. Usually transmitted through bites from mosquitoes, the virus finds its natural hosts in birds.
The burden of disease
From a US perspective, the authors comment that since initial detection of WNV in the country in 1999, it has become the “leading cause of domestic arthropod-borne viral (arboviral) disease”. According to CDC data it has caused more than 55,000 cases of human disease and 2,600 deaths between 1999 and 2021.
“In addition to morbidity and mortality, WNV disease results in substantial costs to patients and society.”
The estimated hospital costs per year reach an average of $59.9 million for the 3109 California residents hospitalised between 2004 and 2017. However, the threat is not limited to the US; it is an “ongoing public health threat” across the world.
Containment and prevention efforts
The authors recognise the “development and expansion” of WNV-specific surveillance and control programmes. Despite these, a “consistently high burden of disease” continues throughout the US each year. Unfortunately, the occurrence at a subnational level is “both geographically focal and sporadic”, which makes it difficult to anticipate outbreaks.
Current preventative efforts include “personal protective measures to reduce vector exposure” and “community-based mosquito control programmes”. However, these approaches are limited according to the authors, who suggest that adherence is “often low”. Reactive programmes are effective but are “costly” and “typically initiated only after many cases”. Additionally, proactive strategies are hard to implement.
Vaccines for horses not humans
Several veterinary vaccines for WNV have been licensed. However, no human vaccines have progressed past Phase I or II clinical trials. The authors identify “several factors” as hindrances to progression. These include “challenges with designing and implementing efficacy studies”, safety concerns, and anticipated costs. Thevchallenges are “not unique” and can be overcome with solutions used for other vaccines, such as “alternative licensing pathways”.
The paper concludes that the past two decades have “demonstrated that current prevention strategies are not enough”.
“WNV vaccination would be more effective in preventing WNV disease and related deaths. Lessons from the development of other vaccines can be applied to move WNV vaccine candidates further through development to ensure the availability of safe and effective vaccines.”
To read the complete article click here. For more on disease prevention and vaccines make sure you have subscribed to our weekly newsletter.
The UK Health Security Agency (UKHSA) published data in May 2023 that reveal a rise in measles cases, mostly in London. Some have been identified in other areas of the country and others are linked to international travel. As the number of children vaccinated against the highly infectious disease has fallen over recent years, UKHSA is encouraging people to check their children’s vaccination history.
Measles on the rise
In November 2022 the WHO described measles as a “growing threat” due to decreasing uptake in the vaccine that protects against measles. The new data suggest that from the start of the year to 20th April there have been 49 cases of measles. This, compared to 54 cases in the whole of the previous year, is a concerning increase. UKHSA indicates that uptake for the first dose of the MMR vaccine, protecting against measles, mumps, and rubella, in children aged 2 in England is 89%. Uptake of 2 MMR doses in children aged 5 is 85%, “well below” the 95% target set by WHO. This target has been set to achieve sustained elimination.
UKHSA recognises that the COVID-19 pandemic presented significant barriers to routine immunisations globally. However, as we emerge from the pandemic, many children remain unprotected against serious infections as the UNICEF State of the world’s children report details. With measles circulating in many countries around the world, WHO is warning that Europe may see a resurgence.
In the UK children are offered the first dose of the MMR vaccine at 1 year of age, with the second following at 3 years and 4 months.
“UKHSA is urging parents of young children, teenagers, and adults to check they are up to date with the MMR vaccines.”
Dr Vanessa Saliba, Consultant Epidemiologist at UKHSA, echoed this call:
“It’s never too late to catch up, and you can get the MMR vaccine for free on the NHS whatever your age.”
Dr Saliba described vaccines as “our best line of defence” against diseases like measles. Steve Russell, the NHS Director of Vaccinations and Screening, described the NHS’ “inspiring history of successful vaccination programmes”. These have “proven time and again” that they are the “best tool in our arsenal”.
“I strongly urge parents to review the status of their child’s vaccinations so they can keep them and others protected.”
In May 2023 the US FDA announced approval of Arexvy, the first respiratory syncytial virus (RSV) vaccine to be approved for use in the US and the rest of the world. It has been approved for the prevention of lower respiratory tract disease caused by RSV in patients aged 60 and above. This is a momentous moment, not only for GSK, but for global efforts against RSV, which can be deadly in older people.
As we have previously explored in older posts, the burden of RSV is largely shouldered by older people. Although it usually causes milder symptoms for young people, the CDC suggests that it kills between 6,000 and 10,000 adults over the age of 65 in the US. Apart from this, it results in between 60,000 and 160,000 hospitalisations.
Dr Barney Graham, senior advisor for global-health-equity trials at Morehouse School of Medicine in Georgia, told Nature that the possibility of having “options available to prevent RSV disease” as a “very big deal”.
Dr Peter Marks, director of the FDA’s Centre for Biologics Evaluation and Research recognised the approval as an “important public health achievement”. Dr Marks suggests that it reflects the organisation’s “continued commitment to facilitating the development of safe and effective vaccines for use in the United States”.
Sprint finish to the marathon
Nature states that “the technology underlying the RSV vaccine” has been “almost 60 years in the making”. From a critical trial in the 1960s, which killed two participating children and hospitalised 80%, to this day, it’s been a long journey. Dr Graham notes that “the first 20 years were spent primarily working out how to make a vaccine that could be safe”.
In 2008, Dr Graham began a collaboration to better understand the structural biology of the virus, learning that it used protein F to infect a host’s cells. Thus, protein-based vaccines could be developed to elicit a response. However, the team found that early protein-based vaccines were designed around the “wrong form of protein F”, which forms after the virus and cell have already joined. Therefore, the target became the correct form, which hadn’t fully fused with any cell.
Research published in 2013 allowed companies like GSK to pursue their vaccine candidates. Dr Graham is delighted that his “lifetime’s work” is coming to fruition.
“It’s very gratifying to see this finally happening.”
Although the vaccine has been a long time coming, experts are hoping that others will quickly follow suit. For example, Pfizer’s candidate, a protein-based RSV vaccine for older patients awaits approval, and Moderna has an mRNA candidate under expedited review.
Our next interview in the exclusive Congress series is our conversation with Gabriella Hakim. Gabriella is the CEO and a Co-Founder of VacTrack, one of our start-ups at the Congress! It was exciting to get an insight into the work that she and her team are doing to provide digital solutions to the vaccine community. We also heard more about her experience of leading a start-up into the vaccine industry. We are grateful to Gabriella for her time and energy, and hope you enjoy this perspective.
Gabriella describes VacTrack as a “fully patient-centric” app that “aims to empower individuals to take ownership over their own immunity health”. Through the app your profile is offered “digital storage”, recommendations, reminders, and alerts. It also hosts multiple profiles, which allows parents to track their children’s immunisation schedule as well.
“Improving access, improving adherence, to vaccinations through a digital solution.”
A digital solution
As Gabriella has mentioned, this is a “digital solution” to immunisation. We asked her to tell us more about how this works. Not only can you get information and recommendations, but the app also facilitates booking. By “letting patients take control” of their immunisation schedules, VacTrack are hoping to tackle the “barrier” of lack of information and support. Furthermore, all of this is available “at the tips of [patients’] fingers”.
Education and empowerment
On the subject of barriers, we asked about vaccine hesitancy. Throughout the pandemic we have seen an increase in misinformation and confusion about vaccines, which creates hurdles in the path to immunisation goals. For Gabriella, the key contribution from VacTrack to overcoming vaccine hesitancy is “education”.
“We’ve created a user-friendly experience, that gives you personalised guidance.”
From travel vaccines to routine childhood immunisations, the app “tells you exactly what you need to get and when”.
“So it’s providing and empowering patients with an individualised approach.”
This “individualised approach” cuts through the confusing and sometimes conflicting guidance to offer a personal programme.
Shaking up the system
Although the app sounds incredibly useful and user-friendly, new innovations are hard to implement in established communities. However, innovation is key to progress, so we were keen to hear how receptive Gabriella and her team have found the vaccine world. Is it resistant or open to change?
“It’s been a bit of both”
Gabriella suggests that a lot of people are impressed with the concept and “wish this existed before”! On the other hand, trying to implement the programme is a challenge, and despite meetings with the UK government and the NHS, the team is learning the importance of establishing and nurturing contacts.
“Finding the right contacts is one of the biggest obstacles.”
Luckily, most of Gabriella’s experience so far has been “encouraging”, and we hope that the Congress contributed to this!
Advice for start-ups
As VacTrack joined us in our start-up zone at the Congress, we were interested to hear from Gabriella what she has learnt so far, or how she hopes to build within the vaccine space. Her key message is that “you have to learn to pivot, to be malleable”. She indicates that she has tried to be receptive to advice and constructive criticism to get this far.
What does the Congress offer?
VacTrack is the first start-up we have interviewed, so we were particularly interested to learn what Gabriella was hoping to get from the event. She emphasises the importance of networking. As she has already mentioned, contacts are key for the early and exciting stages of a growing business.
“It’s been a privilege to meet so many amazing, incredible people here .”
It’s great to hear that the Congress facilitates some of these connections.
Thank you so much to Gabriella for her time and insight – we hope that other start-ups or potential partners enjoy the interview! To learn more about VacTrack or get involved, visit their website.
If you are interested in joining the start-up zone at our European event in Barcelona later this year, click here. For start-up opportunities at our West Coast event, click here. Finally, to join us in Washington next year, click here.
Research shared in Nature in May 2023 details work by a team from Baidu Research to develop an AI algorithm that can efficiently design highly stable COVID-19 mRNA vaccine sequences. The algorithm is called LinearDesign, and achieved a 128-fold increase in the vaccine’s antibody response. The paper, currently unedited, has been made available in the publication to “give early access to its findings”.
Baidu’s “major leap”
In a statement from Baidu Research the company described this research as a “major leap” for vaccine sequences. It came about through a collaboration with Oregon State University, StemiRNA Therapeutics, and the University of Rochester Medical Centre. The company states that the publication, shared through Accelerated Article Preview (AAP), marks the “first time a Chinese tech company has been credited as the first affiliation on a paper published in Nature”.
“The paper reveals how a complex biology problem can be tackled by taking a classic approach from natural language processing (NLP), using an elegantly simple solution that has been employed to understand words and grammar.”
Instability and insufficient protein expression
During the COVID-19 pandemic, mRNA has made its name as a “revolutionary technology” for vaccine development. Baidu describes it as a “vital messenger” that carries “genetic instructions from DNA” to the “cell’s protein-making machinery”.
“mRNA enables the creation of specific proteins for various functions in the human body.”
Furthermore, it has “numerous advantages” from safety to production, which allowed its adoption for use in the pandemic. However, “natural instability” results in insufficient protein expression, which “weakens a vaccine’s capacity to stimulate strong immune responses”. This also presents challenges for storage and transport, particularly in developing countries.
Baidu indicates that previous research into optimising the secondary structure stability of mRNA, when combined with optimal codons, has led to improved protein expression. However, the challenge “lies in the mRNA design space”. Due to “synonymous codons”, this is “incredibly vast”.
Although NLP and biology appear unrelated fields, they share “strong mathematical connections” according to the team at Baidu. They compare human language, which comprises a word sequence and underlying syntactic tree to convey a meaning, with an RNA strand. This has a nucleotide sequence and “associated secondary structure” based on the folding pattern.
The team used lattice parsing, a language processing technique, which represents potential words connections in a graph and selects the most likely option based on grammar. Manipulating it for mRNA purposes, the researchers created a graph that “compactly represents all mRNA candidates” using deterministic finite-state automation (DFA).
With this process LinearDesign takes “a mere 11 minutes” to generate the most stable mRNA sequence that encodes Spike protein. When compared to existing vaccine sequences the sequences designed by LinearDesign demonstrated “significantly improved results”. For COVID-19 sequences the algorithm achieved up to a 5-fold increase in stability, a 3-fold increase in protein expression within 48 hours, and an “incredible” 128-fold increase in antibody response.
Dr He Zhang, Software Engineer at Baidu Research, hopes this work can apply mRNA medicine encoding to a “wider range of therapeutic proteins” with the promise of “broad applications and far-reaching impact”.
“The vaccines designed through our method may offer better protection with the same dosage, and potentially provide equal protection with a smaller dose, leading to fewer side effects.”
Dr Zhang hopes this will “greatly reduce the vaccine research and development costs” while “improving the outcomes”. Baidu emphasises that it will keep exploring the AI applications in life sciences, hoping to broaden the “scope and depth of inclusive technology”.
“Championing the health and well-being of all humanity.”
For more technological advances in vaccine development, head to our technology section or subscribe for regular updates in your inbox!
As part of our series of exclusive interviews conducted at the World Vaccine Congress this month we are delighted to share our conversation with Dr Jomana Musmar. Dr Musmar serves as Designated Federal Officer for the Presidential Advisory Council on Combating Antibiotic Resistant Bacteria (PACCARB), which she has been managing since its conception in 2015. She is also the Senior Public Health Advisor in the Office of Infectious Disease and HIV/AIDS Policy (OIDP), Office of the Assistant Secretary for Health, HHS. She kindly made time during her Congress schedule to discuss AMR and One Health. We are grateful for her time and insights, and hope you enjoy this interview!
Introducing Dr Musmar
Dr Musmar’s roles are quite the mouthful, so we were impressed that she delivered such a concise introduction in one breath! She joined us at the Congress to explore how we can prepare for a future pandemic in the “era of AMR” and to participate in a panel that brought a governmental, agency, and regulatory perspective to vaccines for AMR.
Why One Health?
Many members of our community will be familiar with the term ‘One Health’, which WHO describes as an “integrated, unifying approach”. It draws on knowledge from animal, human, and environmental disciplines in pursuit of a sustainable and balanced result. Dr Musmar explains that is more than an approach, but a “holistic way of integrating” the “human, agricultural, and environmental domains of health”.
“The impacts of one affect the others as well.”
This is not only reflected in the proceedings of Dr Musmar’s Council, but the membership.
“We all sit at the same table.”
Since the establishment of the Council, “every single report” has had at least a human and animal health component, with an increasing focus on environmental health.
Communication is key
As Dr Musmar highlighted the importance of including all relevant experts at the table, we asked about how this works in her daily practice. She shared with us that at the time of establishing the council in 2015, involving everyone was “always a challenge”.
“The areas were very siloed until we finally broke those barriers.”
In spite of the apparent “biases” and “controversies” that might have been instinctual obstacles to progress, Dr Musmar and her team were able to demonstrate that “there is a common thread”. Thus, camaraderie developed, and is reflected in the makeup of the council and its questioning.
“There’s so much interaction and communication, and we always use up our discussion time because there’s so much information that can be shared and learnt on all sides.”
Going forward, Dr Musmar and her colleagues are hoping to “normalise the dialogue”, further extending to the environmental domain. For those of us who aren’t entirely sure what “environmental” covers, she explains that it involves more than just plant and crop health: “we’re talking climate change as well; we’re talking wastewater management”.
“Ultimately, the dialogue always circles back to ‘how does it impact human health’ but we want to make sure that the focus also is centred on ‘how does it impact animal health and environmental health as well?'”
Access and AMR
We know from other speakers that health efforts and interventions are worth nothing if they are only available to some. We therefore asked Dr Musmar how access and sustainability play into what she does. Helpfully, she referred us to a recent report, which you can access here, which discussed “four particular domains that need attention”.
These include, in her personal opinion, the most important: “ensuring that we have a robust workforce”. Incentivising, integrating, and supporting health workers is crucial to any health response, she argues. Finally, Dr Musmar explores the importance of “antibiotic stewardship”, which ensures that guidelines and practices are sustainable when we encounter fear or uncertainty during a pandemic.
In the report, the “foundation” is “establishing trust” in order to ensure equity. Dr Musmar uses the example of the COVID-19 pandemic, during which adults were a focus group. This excluded children and other “pockets” who may have been forgotten. In the future, they must be brought into the equation from the start, says Dr Musmar, if we are to achieve equity in future responses.
What are you looking forward to?
We concluded our interview with a question about what Dr Musmar was most looking forward to at the Congress. For her, the opportunity to share her recent report is exciting, and she was looking forward to emphasising the importance of One Health in tackling AMR.
“Seeing people’s perspectives and reactions to what the report says.”
We hope that this interview offers a unique perspective and that you find it as interesting as we did! Thank you once again to Dr Musmar for her time and enthusiasm. For more on what went on at the Congress, click here for a post-Congress report and make sure you subscribe for further Congress insights.
Shortly after the publication of UNICEF’s State of the World’s Children report in April 2023, UNICEF explored the reasons for its procurement approach: pooled procurement. Through this approach UNICEF delivers over 2 billion vaccines for children. These protect against diseases like measles and polio.
Pooled procurement is a process that allows UNICEF to forecast and combine vaccine demand to “get better commercial terms from manufacturers” than would be available to individual countries.
“It gives suppliers a long-term sense of the doses required, allows for large-scale production of vaccines, and helps UNICEF to get competitive prices by asking manufacturers to submit proposals for supply.”
In this post we look at the 5 reasons that UNIEF presents for this approach.
UNICEF works with countries to “estimate expected vaccine requirements” for the future, procuring childhood vaccines for 45% of the world’s children under 5. It can therefore plan for supplies to be available with manufacturers who need long-term visibility. As vaccine production is a complex process it can take up to 2 years, so this visibility is helpful.
In the tendering process manufacturers submit details such as pricing, cold chain requirements, and yearly dose availability. Next, UNICEF evaluates the commercial offers while WHO reviews the technical aspects. Before contracts are signed UNICEF can negotiate with suppliers.
“The ideal mix of vaccines and suppliers is determined by factors such as the suitability of vaccines for the country context, pricing, delivery times, production capacity, and geographical distribution of the suppliers.”
Pooled procurement also offers “significant benefits by allowing countries to access vaccines at lower prices” than could be achieved through individual negotiations. Economies of scale enable manufacturers to reduce costs and streamline processes over larger volumes and extended periods. Furthermore, they only need to deal with one buyer.
UNICEF is the “largest single vaccine buyer” in the world. It therefore works with partners to “ensure vaccines markets remain healthy”. This means considering more than “pricing and production schedules”. For example, the organisation emphasises the importance of having more than one manufacturer of each vaccine to ensure that prices and supply are stable.
To do this, UNICEF evaluates proposals to reduce market barriers. Additionally, it works with new suppliers and encourages them to join the market “when appropriate”.
Partnering for progress
“UNICEF does not work alone.”
With a combination of donor funding, vaccine industry consultations, and competitive tenders, UNICEF secures access. It also works in collaboration with partners like the Global Polio Eradication Initiative and the Measles and Rubella Initiative. UNICEF is also a member and the “main procurement agency” of Gavi.
“Only through regular collaboration can UNICEF continue to reach children with the vaccines they need.”
A success story: the pentavalent vaccine
Considering one example as evidence that pooled procurement is effective, UNICEF explores the history of the pentavalent vaccine. This protects against “five potentially fatal diseases”: diphtheria, tetanus, pertussis, hepatitis B, and haemophilus influenzae type b.
In 2001 only one manufacturer produced it, meaning that there were “insufficient doses” for every child in need. By 2007 there were two suppliers, but the price per dose was still at $3.50. With funding from Gavi and efforts from UNICEF, demand was consolidated and opportunities for manufacturers to enter the market were created.
Now, with “ongoing efforts” to sustain a healthy vaccine market, four manufacturers supply the vaccine to UNICEF, with the lowest price at $0.78 per dose. This is almost 80% lower than 2007.
“Pooled procurement, alongside UNICEF’s efforts to shape a healthy market, enables equitable access to lifesaving vaccines for every child.”
What benefits can you see to pooled procurement, and how can it be implemented most effectively to provide for those who need vaccines most?