As the countdown to the World Vaccine Congress in Washington continues with only days to go, we are excited to share another pre-event interview. This conversation with Dr Fadil Bidmos was conducted over email and gives us an insight into what he will be exploring during his session in the AMR workshop on the 3rd of April. We are so grateful to Dr Bidmos for his time and the detail he offered in his answers. We hope you enjoy the interview!
Introducing Dr Bidmos
Dr Bidmos is an Advanced Research Fellow at Imperial College London, directing “innovative research” that is focused on the development of a vaccine that targets “both main causes of bacterial meningitis”: Neisseria meningitidis and Streptococcus pneumoniae. Dr Bidmos explained that bacterial meningitis “mostly affects children under the age of 5 and the immunocompromised”.
The “rapid pace of progression of disease” and “non-specificity of early symptoms” ultimately leads to death, which is why there is a significant need for preventative measures as an alternative to post-infection therapy. This research is funded by Dr Bidmos’ MRC Career Development Award and uses “advanced pre-clinical strategies” with the goal of designing “cost-effective” vaccine candidate antigens. The intention is then to extend these strategies to other bacterial diseases.
Alongside his research responsibilities, Dr Bidmos teaches and supervises the laboratory projects of university students, as well as executing administrative tasks within the College.
“I contribute to the wider community by reviewing and editing journal manuscripts in the area of bacterial infectious diseases, and review of grant applications for both national and international agencies.”
Reverse Vaccinology 2.0
Dr Bidmos will present a session on “Reverse Vaccinology 2.0” at the Congress next week. We asked about a general perspective but also how this can be considered in the context of AMR prevention. He suggests that it is an “update on the previous Reverse Vaccinology strategy”.
“One can see it in the same light as the software updates required for computerised devices.”
A key difference is that “candidates recommended by RV studies are not necessarily known to be immunogenic in humans”. However, “because of the nature of RV2.0”, we can make a “solid assumption” about the immunogenicity status of RV2.0 antigens.
“In the context of AMR, RV2.0 is a powerful tool that can unravel vaccine antigens at a rapid pace, but more importantly, the RV2.0 strategy can also yield an alternative agent – therapeutic antibodies – which can be used for treatment of cases of significant multidrug resistance.”
Why is RV so useful for public health threats?
A quick google search reveals that many consider RV to be an improvement or advancement on ‘traditional’ vaccinology. We therefore asked Dr Bidmos about the advantages it brings to the public health sphere.
“One of its main advantages is pace of antigen discovery. Given the appropriate facilities and robust study design, candidate vaccine antigens for a pathogen can be discovered in about 2 months.”
Another advantage is the “quality of antigens”. In Dr Bidmos’ experience, it reveals “rare but highly immunogenic antigens which would be missed by traditional approaches because of our limited knowledge and adherence to paradigms that correspond to theoretical assumptions”
“Here lies another strength of RV2.0 – its non-bias for ‘antigens’ as defined by our limited understanding.”
At the cloning stage, the maximum number of antibody-producing cells will be sorted. As Dr Bidmos suggests, “the bigger the lab/human resources, the better”, for this stage.
“Because the cognate antigen antigens of antibodies produced by each cell is unknown, there is a much greater likelihood that novel antigens, including those that would have never been considered by traditional hypothesis-based/RV approaches, will be discovered.”
On that note, Dr Bidmos acknowledges that “even classical RV” is “susceptible to missing rare antigens” because it relies on “our assumptions of an antigen’s characteristics”.
Technological advances and areas for improvement
Over the past few years, the speed of technological change has been noticeable even to the untrained observer, so we asked Dr Bidmos about areas that have been important for RV and areas for more attention. Although not so recent, he recalls “advancements in fluorescence-activated cell sorting equipment” and “the availability of whole genome sequence data” as “critical” to “high-throughput strategies” like RV2.0.
“Further advancements in automated solutions will greatly enhance its capacity – while powerful, RV2.0 can be labour-intensive, especially when its full benefits are desired.”
These solutions will be particularly important for “basic lab tasks”. Dr Bidmos considers things like “agarose gel electrophoresis of 1000s of samples and cloning”. On a “less technical but more crucial level”, Dr Bidmos states that identifying correlates of protection for individual pathogens requires “significant effort”. Without these correlates, the “determination of what constitutes functional immunogenicity will remain unknown”.
“If we can’t delineate cloned antibodies based on functional ability, how will we select which cognate antigens to take forward?”
AMR and access
Access should always be central to vaccine development, but for AMR it is particularly relevant. Thus, we should be ensuring that vaccines used in AMR prevention efforts should be accessible to all. We asked Dr Bidmos about challenges that are associated with establishing cost-effective processes to produce accessible products.
Dr Bidmos began by suggesting that some aspects of this herculean task “go beyond science”. However, he tactfully opted to “stick with science-y bit”. Perhaps if you meet him at the Congress, you can dig deeper into these other factors with him!
The cost of vaccine research and development, especially with “advanced technologies”, is “not cheap”. Referring to a study from 2018, Dr Bidmos tells us that the cost of progressing just one vaccine from “pre-clinical through to Phase IIa trial completion” was between $319 and $469 million, accounting for “risk of failure”.
“Perhaps, further funding support, if available, from intergovernmental networks could help support industry in offsetting some costs in the vaccine development process, thus limiting the burden on industry and their need to recoup expenses by setting high prices for vaccines that make it to market.”
“Cross-talk between regulatory bodies for knowledge sharing may help eliminate bottlenecks in licensure (following due processes, of course) for diseases with little to no vaccine licensure track record.”
For example, Dr Bidmos identifies a “wealth of experience” in the meningococcal vaccine regulatory field that could be “somewhat useful to other disease regulatory bodies”.
“Finally, scientists like myself who are at the heart of the development process can continue to apply new knowledge (some of which is obtained from ‘blue skies’ research, an area suffering from limited funding) to the development of processes that can help industry overcome manufacturing bottlenecks.”
Looking forward to next week!
With the Congress just days away we were eager to hear what Dr Bidmos is excited about. For him, the call of “new technologies” is strong; he’s looking forward to meeting them and exploring how their products and services can take his research to the “next level”.
“I am also excitedly looking forward to gaining a deeper understanding of what goes on at the other side of the lab door, i.e., when we finish our bit, and the product goes to industry, what processes are involved in transforming our research into the final product.”
We hope that you found Dr Bidmos’ insights useful and are encouraged to attend his workshop for more information. Thank you to Dr Bidmos for his time and participation in our exclusive interview series! For more like this, keep an eye on your inbox over the next few weeks!
After experts called for “transformational change” to the “epidemic countermeasures ecosystem” in March 2023, our interest has been drawn to an initiative by Economist Impact: The Vaccine Ecosystem Initiative. This is described by the group as an attempt to “promote a sustainable vaccine ecosystem” by “examining and reimagining elements critical for vaccine development, deployment, and adoption”. From the context of a global pandemic to the concerning epidemiological climate, the initiative explores current practices to define the future of vaccines at every stage.
Why an ecosystem?
The use of the word ecosystem is particularly effective with connotations of complexity and interconnectivity. From concept to shot in arm, ‘ecosystem’ evokes a sense of delicate dependency at every stage. Indeed, recent experiences have emphasised these relationships more than ever.
“Building an environment conducive to innovation can reinvigorate a previously undervalued field of science.”
5 key pillars
In a report published by Economist Impact, 5 key pillars are identified. For greater detail on each pillar, we recommend accessing the report here. In this piece we explore the pillars and invite you to share your thoughts on this framework.
Research and Development (R&D)
The first pillar covers the research process from the “earliest stages of laboratory research through the Phase III (human) clinical trials” and the regulatory oversight that is “necessary for supporting vaccine development and innovations”. It also addresses the R&D needed to support the delivery of vaccine services, such as disease surveillance, policies, and partnerships.
Manufacturing
The second pillar is all things manufacturing, exploring the factors of “timely” processes, regulatory oversight, and “the use of good manufacturing practices at a scale necessary to meet demand”. It covers infrastructure, human resources and conditions, and strict quality control standards.
Procurement, pricing, and financing
The third pillar involves the policies, mechanisms, and partnerships behind vaccine purchasing and pricing. This includes the financing of R&D and implementation of immunisation programmes. Systems that “promote more equitable and faster access to vaccines” are of interest.
Distribution, logistics, and supply chain management
The fourth pillar covers the mechanisms that “enable safe distribution of vaccines”. This includes logistics, infrastructure, and systems. This pillar “recognises that consistently strong and resilient distribution networks, logistics capabilities, and global supply chain management” are needed for equitable and rapid protection of populations.
User acceptance and uptake
The fifth pillar explores the reasons that people choose to be vaccinated and the factors that enable them to access vaccination. This involves health literacy, education and awareness, and the ways that “public trust in vaccines” can be improved.
How well do you think these pillars represent the vaccine ecosystem, and what efforts do you think can be made in any or each of them to promote sustainable improvements?
The Immunisation Readiness Index
Building on this framework, the Vaccine Ecosystem Initiative will launch a new tool later this year, focused on “understanding the state of immunisation readiness”. The Immunisation Readiness Index assesses the “enabling environment for equitable and sustainable immunisation” for both routine and emergency vaccines. The Index identifies “opportunities for enhanced preparedness” by “qualitatively and quantitatively mapping” country-level immunisation policies.
“The Vaccine Ecosystem Initiative and the Immunisation Readiness Index provide evidence-based, actionable insights that stakeholders can implement to create a future that is more resilient to threats amenable to vaccination.”
Join us at the World Vaccine Congress in Washington next week to hear more from David Humphreys, Global Head of Policy at Economist Impact.
After a meeting in March 2023, WHO’s Strategic Advisory Group of Experts on Immunisation (SAGE) revised the roadmap for prioritising COVID-19 vaccines. This result is intended to “reflect the impact of Omicron and high population-level immunity” through infection and vaccination. WHO states that the roadmap “continues SAGE’s prioritisation of protecting populations at the greatest risk” from SARS-CoV-2 infection and its “focus on maintaining resilient health systems”.
Cost and context
The roadmap now considers “cost-effectiveness” of vaccination for lower-risk groups, such as healthy children and adolescents, in comparison with “other health interventions”. It also includes revised recommendations on boosters. SAGE Chair Dr Hanna Nohynek reflected that “much of the population” has either received vaccinations, been infected, or both. However, the roadmap “reemphasises the importance of vaccinating those still at-risk of severe disease”.
“Countries should consider their specific context in deciding whether to continue vaccinating low risk groups, like healthy children and adolescents, while not compromising the routine vaccines that are so crucial for the health and well-being of this age group.”
The roadmap presents a recommended prioritisation system for COVID-19 vaccination. The levels are high, medium, and low, and are “principally based on risk of severe disease and death”, consider “vaccine performance, cost-effectiveness, programmatic factors, and community acceptance”.
Priority groups
The high priority group includes older adults, younger adults with “significant comorbidities”, such as heart disease, people with immunocompromising conditions, such as people living with HIV or transplant recipients, children aged 6 months and older, pregnant people, and frontline health workers.
For this group, SAGE is recommending an “additional booster” of either 6 or 12 months after the last dose, with the timeframe “depending on factors such as age and immunocompromising conditions”. It emphasises this advice applies for the “current epidemiological scenario only” and should not be seen as for “continued annual” boosters.
“The aim is to serve countries planning for the near- to mid-term.”
The medium priority group covers healthy adults, usually younger than 50 or 60, without comorbidities, and children and adolescents with comorbidities. SAGE suggests that this group should be offered primary series and first booster doses but does not routinely recommend additional boosters “given the comparatively low public health returns”.
The low priority group includes health children and adolescents between the ages of 6 months and 17 years. Primary and booster doses are “safe and effective” in this group, but the consideration of the “low burden of disease” led SAGE to urge countries to “base their decisions on contextual factors”.
“The public health impact of vaccinating health children and adolescents is comparatively much lower than the established benefits of traditional essential vaccines for children – such as the rotavirus, measles, and pneumococcal conjugate vaccines”.
Other meeting considerations
During the meeting SAGE also considered other public health concerns, such as polio and measles. For polio, it evaluated the data on the novel oral polio vaccine type 2 and concluded that it should be the “preferred choice for response to circulating vaccine-derived poliovirus type 2” (cVDPV2) where possible. It also recommended that in “hard to reach or conflict-prone areas” the interval between vaccines could be reduced to 1 week, from the regular 4 weeks.
Regarding measles, SAGE described the “repercussions of the pandemic’s seismic impact on routine immunisation”. Measles cases have increased in all WHO regions in 2022, which prompts the need to review policies on vaccination, and accelerate the development and deployment of new technologies.
The meeting also covered TB concerns, identifying an urgent need for a more effective vaccine for adolescents and adults. SAGE recognised “substantial” efforts towards that end, with “several candidates” in trials.
Another concern during the meeting was the introduction of the RTS,S malaria vaccine, which has “resulted in a substantial reduction in severe malaria and all-cause mortality among age eligible children”. The high demand for the vaccine is at odds with the “highly constrained” supply, with SAGE recommending flexibility in the immunisation schedule.
Priority pathogens
WHO also stated that it is in the process of “defining regional priority targets” for new vaccine development for “non-epidemic pathogens”. Early research suggests that tuberculosis, HIV, and pathogens exhibiting “high levels on antimicrobial resistance” (AMR), are important across “all regions”.
Do you agree with SAGE’s recommendations, and do you think they will have an effect on vaccination efforts in your region? To participate in discussions about COVID-19 vaccination schedules and other pathogenic concerns, join us at the World Vaccine Congress in Washington next week.
A study published in Nature Medicine in March 2023 explores the factors associated with so-called “vaccine fatigue”, with a specific focus on the recent vaccination campaigns in response to the COVID-19 pandemic. The authors state that vaccines are “likely to remain one of the essential tools”. We have developed vaccines that are now “widely available in many countries” and progress in vaccine development has been made. However, the authors acknowledge that vaccines can only be effective if people get vaccinated.
“Unfortunately, several behavioural factors threaten to undercut the advances in vaccine supply and development.”
Previous studies have identified vaccine hesitancy as an “obstacle” to primary vaccinations and decreasing “enthusiasm” for boosters. The study suggests that “vaccine fatigue” has emerged as a “growing concern for public health officials”. In fact, it implies that this is a re-emergence rather than a unique phenomenon, already familiar from the “influenza context”, where “suboptimal uptake has repeatedly resulted in many unnecessary deaths”.
“It is very likely that the failure to address vaccination hesitancy and fatigue could have serious public health consequences in the long run and, in turn, increase pressure on healthcare systems.”
Understanding COVID-19 vaccine fatigue through the study
The study addresses two “practically and theoretically relevant research questions”.
Should vaccination campaigns adopt similar or different strategies for primary and booster vaccinations?
What are the most relevant contextual features and the most effective interventions that may affect vaccine acceptance in future scenarios?
The aim of the study was to gather evidence for the design of “effective” campaigns in the context of the “heterogeneous immunisation status in the population” and “possible contextual contingencies”.
The researchers designed two conjoint experiments, which allowed them to manipulate “multiple attributes of a hypothetical scenario” and “measure the responses of participants considering all attributes jointly”. A literature review demonstrated that the most important factors for COVID-19 vaccine uptake were the properties of vaccines, communication, costs/incentives, and legal rules.
Fatigue and hesitancy
The authors note that vaccine fatigue, in addition to the challenge presented by vaccine hesitancy, is a “growing concern” for public health due to “waning immunity” and the requirements for booster vaccinations considering new variants. They suggest that in “many countries” the uptake of boosters has remained “below expectations”.
Although the definitions of vaccine hesitancy and vaccine fatigue remain unclear across literature and media communication, the study refers to both in a “broad sense as an umbrella term”. This term describes a “low or intermediate propensity to get vaccinated either for the first time (hesitancy) or repeatedly (fatigue)”. The term covers those who are “in a state of indecision or uncertainty” but also those who “oppose and refuse vaccination”. However, the authors acknowledge that “more narrow conceptions coexist”.
The first question
The first question addressed the approach that should be taken for future vaccination campaigns; should they be a “one-size-fits-all” approach or should “group-specific characteristics” be taken into account?
The results suggest that distinguishing campaigns between primary and booster vaccinations is the best approach, in line with early pandemic research. However, the study builds on this previous research by showing “additional variation” between those who have not had a first booster and the “triple vaccinated”, suggesting that “further group differences may need to be considered”.
The results also indicate international differences. For example, the relevance of information on Long COVID mattered more in Austria than in Italy.
“These patterns underline our first piece of actionable advice that instruments of vaccination campaigns need to be tailored and tested before campaign rollout, taking into account characteristics of the national context and the different target groups based on their vaccination status.”
The second question
The second question explored how different groups “can and should” be addressed by campaigns. Although “from a medical perspective” the importance of closing the vaccination gap and focusing on the unvaccinated seems a priority, the authors state that this may be difficult. The unvaccinated score “low on trust in institutions” and are the “least likely to get vaccinated across all scenarios”. The study considers that the countries involved, Austria and Italy, had both considered some type of vaccine mandate during the pandemic, and therefore “most of those who can be reached by vaccination campaigns have already been vaccinated”.
“Only campaign messages conveying a sense of community and emphasising the need to hold together to overcome the crisis were effective in promoting behavioural change in the unvaccinated group.”
By contrast, legal rules such as mandates or vaccine passports were found to “undermine” trust in the vaccine. These results suggest that the “most socially agreeable way to encourage primary vaccinations” would be a focus on “promoting community spirit” over “stricter policy interventions”. Furthermore, it is “essential” to address the factors that contribute to vaccine hesitancy, such as mistrust and misinformation.
People who had been vaccinated once or twice were “strongly encouraged by positive incentives” such as monetary perks, and the availability of new vaccines. The latter was “only marginally statistically significant” but suggests the need to promote “better understand of heterologous vaccinations” and to obtain regulatory approval for new non-mRNA vaccines as boosters.
Triple vaccinated people
For those who were triple vaccinated, the authors considered the possibility that incentives and strategies may seem a “superfluous exercise”. It would be easy to act under the assumption that they will go and get the “necessary boosters” under “any circumstances”. However, the results suggest otherwise, with “seemingly trivial costs” presenting an obstacle to the triple vaccinated that might deter them from “translating their positive attitudes into actual behaviour”.
“We found a high degree of cost sensitivity among the triple vaccinated.”
This was reported as the “strongest effect” across the experiments and “most consistent” in both Austria and Italy.
“Cost-free and easy access to vaccines as well as creating awareness of when and how to get the vaccine, therefore, are likely to remain the mainstay for any vaccination campaign to succeed.”
Other factors that influence the triple vaccinated group are messages emphasising personal health benefits, the importance of “protecting vulnerable peers” and the healthcare system, as well as “community spirit and self-efficacy”. As this group represented the largest population in both countries, failure to “(re)activate and (re)mobilise” them is likely to result in poor booster rates.
What does the study show?
The authors conclude that the results present “several actionable points”:
Test the design and instruments of vaccination campaigns with target groups
Keep the cost-free provision of vaccines and easy access to vaccination sites in which even seemingly trivial costs could be strongly discouraging
Promote community spirit and set measures to strengthen social cohesion and institutional trust in the long term
Consider moving from communicative mobilisation to more institutionalised bonus programmes with positive incentives for booster vaccinations in the long term, if budgetary constraints allow
Carefully assess the risks and benefits of stricter policy instruments involving legal requirements, such as vaccine passports and vaccine mandates, which bear a risk of backlash
Facilitate consensus-building among medical professionals and scientists by supporting research and making relevant evidence readily available
How might these actions be implemented in your community, and do you think will be effective in encouraging vaccine uptake or overcoming vaccine fatigue? We look forward to considering these questions and more at the World Vaccine Congress in Washington next week.
In March 2023 the heads of the Quadripartite organisations working on One Health issued a call for greater global action for a safer world. WHO describes the call as “unprecedented”. The Quadripartite comprises four main agencies collaborating to achieve aims that cannot be achieved independently. The Food and Agriculture Organisation of the UN (FAO), the United Nations Environment Programme (UNEP), WHO, and the World Organisation for Animal Health (WOAH) are all participating in this union.
A statement from the Quadripartite acknowledges recent health emergencies such as the COVID-19 pandemic, mpox, Ebola outbreaks, and “continued threats of other zoonotic diseases” as well as AMR challenges, and the consequences of climate change. These elements “clearly demonstrate the need for resilient health systems and accelerate global action”.
A call to action
The statement from the Quadripartite emphasises the need for “enhanced collaboration and commitment” to “translate the One Health approach into policy action in all countries”. The leaders called for the promotion and undertaking of the following “priority actions”:
Prioritise One Health in the international political agenda, increase understanding, and advocate for the adoption and promotion of the enhanced intersectoral health governance.
Strengthen national One Health policies, strategies, and plans.
Accelerate the implementation of One Health plans.
Build intersectoral One Health workforces.
Strengthen and sustain prevention of pandemics and health threats at source.
Encourage and strengthen One Health scientific knowledge and evidence creation and exchange.
Increase investment and financing of One Health strategies and plans.
“To build one healthier planet we need urgent action to galvanise vital political commitments, greater investment, and multisectoral collaboration at every level.”
How do you think these actions can be implemented at international and national levels, and what support should the Quadripartite be offering to encourage this? We look forward to hearing more about the importance of One Health approaches and how vaccination features into these at the World Vaccine Congress in Washington next week.
In March 2023 the CDC commented on data published in the Annals of Internal Medicine that revealed an “alarming” spread of the emerging fungus Candida auris in healthcare facilities in 2020-2021.It also identified a “concerning” increase in 2021 of the number of cases that were resistant to the antifungal medicine echinocandins. In its statement, the CDC deemed the fungus an “urgent” antimicrobial resistant threat, particularly with its growing resistance to antifungal drugs and its potential to cause “severe infections with high death rates”.
What is Candida auris?
Candida auris (C. auris) is a type of yeast that has been causing “severe illness” in hospitalised patients in several countries. For some patients, it enters the bloodstream and causes serious invasive infections throughout the body. The CDC identifies three main causes of concern associated with the fungus:
It is often “multidrug-resistant”.
It is difficult to identify with “standard laboratory methods” and can be misidentified.
Although first identified in Japan in 2009, C. auris was first reported in 2016 in the US. Since then, a total of 3,270 clinical cases (where infection is present) and 7,413 screening cases (where the fungus is present but not causing infection) have been reported to the end of 2021. The most dramatic increase in cases occurred during 2020-2021. Dr Meghan Lyman, lead author of the paper that presents these results, called for continued efforts to identify and contain infections.
“The rapid rise and geographic spread of cases is concerning and emphasises the need for continued surveillance, expanded lab capacity, quicker diagnostic tests, and adherence to proven infection prevention and control.”
Healthcare settings
The CDC reports that patients in healthcare facilities who have been there a long time, have lines of tubes entering their body, or have previously received antibiotics or antifungal medications appear to be at “highest risk of infection”. The increase in cases is linked to both “poor general infection prevention and control (IPC) practices” but also “enhanced efforts to detect cases”.
“The timing of this increase and findings from public health investigations suggest C. auris spread may have worsened due to strain on healthcare and public health systems during the COVID-19 pandemic.”
Professor William Schaffner of the Vanderbilt University Medical Centre told Washington Post that once the fungi get into a hospital, they are “very difficult to control”.
“They can persist, smouldering, causing infections for a considerable period of time despite the best efforts of the infection control team and everyone else in the hospital.”
AMR and C. auris
A particularly concerning feature of these infections is the growing resistance to specific medications. The CDC offers reassurances that “most” of these infections are treatable with echinocandins. However, some infections have been resistant to “all three main classes of antifungal medications”. When this occurs, multiple classes of antifungals at “high doses” are required.
Vaccine possibilities
With increased media attention caused by the CDC’s warning, eyes are on vaccine developers to see if there are preventative measures that could be taken. On 23rd March 2023, The Lundquist Institute (TLI) announced that it has a vaccine candidate in development. This vaccine has reported been shown to “effectively treat mice” with the fungal infection, with the next step being human clinical trials.
“The vaccine used to immunise mice is composed of dual Candida cell surface antigens, which upon vaccination produce neutralising and immune enhancer antibodies. The vaccine also induces a robust T-cell immunity against the fungus, allowing mice to survive the infection.”
Furthermore, TLI suggests that in combination with antifungal drugs, the vaccine results in an “augmented survival”. Dr Ashraf Ibrahim, Investigator at TLI hopes the vaccine can be produced in “good quantities” for the next stage of clinical trials.
“We now have the capability to protect patients who infected by this deadly pathogen.”
We look forward to discussing the possibilities of AMR prevention at the World Vaccine Congress in Washington next week. Join us by getting your tickets here!
A study released in March 2023 in iScience suggests that COVID-19 infection was a greater factor than COVID-19 vaccination in observed changes to a patient’s menstrual cycle. The researchers identified “substantial public concern” related to “disruption of menstrual cycles”. However, the possible causes, such as vaccination, infection, pandemic-related stress, or lifestyle changes, remain “understudied”. Therefore, it is imperative that further investigation is carried out to gain the relevant knowledge for “advising women about the relative risk of experiencing menstrual disturbance when getting vaccinated against COVID-19 versus infected”.
Vaccines and menstruation
The authors suggest that prior to the pandemic, research into the relationship between vaccination and menstrual cycle health was limited to prophylactic typhoid, HPV, and hepatitis B vaccines. Since the pandemic and associated vaccination drive, prospective studies have found changes in cycle length for participants. Beyond cycle length, other studies have identified “various changes in regularity, duration, and volume”.
“While there is accumulating evidence that COVID-19 vaccination-related menstrual symptoms are associated with small and temporary changes in cycle length, there has been no quantitative assessment of the risk factors for menstrual disturbances following COVID-19 vaccination prior to widespread media attention.”
The paper contrasts the “emerging picture” of a “small effect of COVID-19 vaccine on cycle length” with research into the associations between infection and menstrual cycle changes. This is described as “scarce and inconsistent”.
“A study better powered to evaluate the independent association of SARS-CoV-2 and abnormal cycle changes is better needed to inform vaccination decisions.”
What does the study find?
Based on data collected in the UK “prior to widespread media attention” the study identified that “perceived menstrual cycle changes” after vaccination are “very common” in the context of “international pharmacovigilance standards” (over 10%). Specifically, these perceived changes are “increased for participants reporting a history of COVID-19 disease”, but “decreased among those who use combined contraceptives”.
Furthermore, the authors conclude that “vaccination alone does not lead to abnormal cycle parameters”, but COVID-19 is associated with an “increased risk” of reporting frequent cycles, prolonged periods, heavier flows, and more inter-menstrual bleeding. They acknowledge that the experiences of cycle changes after vaccination are “diverse”.
Facts and figures of the study
The study involved almost 5,000 vaccinated pre-menopausal participants, and the University of Edinburgh describes a “vast majority” of 82% who reported “no menstrual changes”. 6.2% reported “more disruption”, 1.6% reported “less disruption”, and 10.2% reported “other changes”
It is notable that of the 18% who reported changes, the risk was higher among those who smoked, had previously had COVID-19, or who were not using oestradiol-containing contraceptives. The authors then considered a wider population of 12,000 participants, which included participants who had not been vaccinated against COVID-19 as well as vaccinated participants.
“Vaccination alone did not show increased abnormal menstrual cycle factors.”
Is this enough?
The authors recognise that their study is limited, particularly in its reliance on people recalling previous menstrual experiences. Dr Jackie Maybin from the University of Edinburgh identifies a potential for “bias” in those who chose to complete the study.
“Nevertheless, our results are reassuring that COVID-19 vaccination does not cause concerning menstrual changes, and helpful for identifying people who might be at higher risk of experiencing menstrual disturbance.”
Did you observe menstrual changes following COVID-19 vaccination, or has this research encouraged you in the context of widespread media concern? Join us at the World Vaccine Congress next month to discuss COVID-19 vaccination with experts across the community.
After we reported in March 2023 that possibly critical data concerning the Huanan Seafood Wholesale Market had been quietly released on GISAID, the story has developed with researchers and public health leaders challenging China for not sharing them sooner. With senior figures in WHO, including the Director General Dr Tedros Adhanom Ghebreyesus, suggesting that the data “could have – and should have” been shared earlier, questions are being raised about the apparent Chinese obfuscation of global pandemic origin research.
Dr van Kerkhove’s “hell”
In a “condensed” interview with Science Dr Maria van Kerkhove outlined her frustrations at being unable to access sufficient data to draw conclusions about the origins of the COVID-19 pandemic. She stated that WHO had been “calling for any and all data” to be shared, echoing previous emphasis on WHO’s reliance on Member States’ cooperation.
Dr van Kerkhove indicated that these new data do confirm “what has been suspected”: “there were animals at the market that were susceptible to SARS-CoV-2 infection, that the market of course played a really important role”. However, questions remain about where the animals came from and what research was carried out in the early stages of the pandemic.
“None of that information is available.”
Displaying diplomatic caution, Dr van Kerkhove also addressed the tension surrounding lab leak or zoonotic origin. She stated that just because “all hypotheses are on the table” it “doesn’t mean that all hypotheses have equal weight”. She emphasised that WHO is “pushing for more information through SAGO”, including immediate sharing of animal-specific information. She described the sudden glimpse of new information as a challenge to China’s “credibility”.
“It is beyond infuriating and frustrating to be in this position…And that is scary as hell.”
Cooperation from China
Experts have long been demanding greater communication from and with China, including Dr Mike Ryan’s reminder that WHO requires its Member States to direct research. Professor George Gao, who Science suggests “sat on” the data, has been contacted by SAGO but apparently not engaged in dialogue. However, for Dr van Kerkhove, the scenes that are unfolding “in social media and in media” are deeply concerning. She hopes to see a conversation “playing out with a robust debate with everything on the table”.
“We don’t have the cooperation from China.”
The “continued fighting” and “politicisation” represents an unnecessary “distraction” from the task at hand, and is “unconscionable”, says Dr van Kerkhove.
Why does it matter?
As we move into a fourth year of COVID-19, armed with evolving vaccine technology and surveillance, some might argue that it is time to abandon this seemingly fruitless pursuit. However, Dr van Kerkhove highlights the importance of “understanding the exact conditions in which this happened” in order to “get more refined” in our approach to prevention. In particular, she identifies a need to understand the specifics of the case in a country “that has excellent lab systems”, “fever surveillance” in place, and “capable scientists”.
Suggesting that “nobody knows” if we will ever know the origin of the pandemic, Dr van Kerkhove reckons that “anyone who speaks with absolute certainty really doesn’t know”. This “clue” is an important one, and one that she hopes to pursue further.
Who owns data?
Although WHO and public health officials have emphatically called for more transparency in data sharing, Science also considers the “appropriateness” of jumping on the data before it has been published in a paper by the Chinese researchers. Indeed, GISAID claimed in a statement on 21st March 2023 that the researchers who identified and analysed the data had been suspended for running “afoul” to the Access Agreement.
GISAID’s statement suggests that “select users” published a report in “direct contravention of the terms they agreed to” with specific emphasis on the “knowledge that the data generators are undergoing peer review assessment of their own publication”. Dr Michael Worobey of the University of Arizona represented the team of authors in a reply to GISAID. He presented email evidence of attempts at collaborations as well as reference to “multiple verbal entreaties” and Zoom messages to the Chinese team.
Consequently, GISAID has agreed to review the evidence, but the question of data ownership and permission continues to sound across media. Dr Jesse Bloom told Science that “all scientific data related to the early outbreak in Wuhan should be made available”.
“It’s frustrating that despite their now being two public analyses related to these data, the data are still not available.”
As we move further away from those first few months of the pandemic, how important do you think it is that we keep trying to understand its origins? What are your views on data sharing and international access?
Join us to discuss how lessons from COVID-19 shape preparations for future threats at the World Vaccine Congress in Washington 2023.
Just under a month after the confirmation of an outbreak of Marburg virus disease (MVD) in Equatorial Guinea in February 2023, the WHO has issued an update confirming further cases. The statement from WHO suggests that 8 additional laboratory-confirmed cases have been reported, bringing the total to 9 confirmed cases and 20 probably cases since the declaration last month.
“There are seven deaths among the laboratory confirmed, and all probable cases are dead.”
Of particular concern to health experts is the observation that the areas reporting cases are about 150 kilometres apart, which WHO identifies as a suggestion of “wider transmission of the virus”. WHO assess the risk posed by the outbreak as “very high at the national level”, “moderate” on a regional level, and “low” at the global level.
Equatorial Guinea “recommitted” to containment
WHO’s Dr Abdi Mahamud commented on the situation, recognising that this is Equatorial Guinea’s first outbreak of MVD. It is therefore experiencing a steep learning curve but must not be tempted to think it “could go away”. Dr Mahamud stated that the country is “recommitted” to containing the outbreak.
Cross-border and case increase concern
As WHO notes, the three affected provinces have international borders with Cameroon and Gabon. These borders are “very porous”, and although no cases have been reported in these neighbouring countries, the “risk of international spread cannot be ruled out”.
Furthermore, concern has been raised over the communication between the health authorities and WHO. Helen Branswell writes for STAT that WHO “typically issues more frequent updates” but relies on information from the affected countries.
“The length of time between this update and the one that preceded it is notable.”
Branswell’s description of the outbreak as “significantly larger than has previously been acknowledged” conveys a sense of the anxiety around accurate and timely communication. She contrasts this to quick disclosures from Tanzanian officials as the country also grapples with an outbreak.
We will hear more about vaccine development for Marburg and other filoviruses at the World Vaccine Congress in Washington, where there will also be opportunities to explore the importance of surveillance and transparency in disease outbreaks.
A study in Microbiology Spectrum in March 2023 demonstrated the benefits of an oral vaccine for COVID-19 that could “dramatically improve immunisation rates”. The universal vaccine is based on the nucleocapsid protein, which evolves at a slower rate than the spike protein. It exploits a weakened bacterium to produce the nucleocapsid protein and membrane protein in infected cells. Tested in hamsters, the vaccine displayed safety and potency.
Continuing the fight against SARS-CoV-2
The authors note that the COVID-19 pandemic, caused by SARS-CoV-2, has (at time of writing), caused over 585 million cases and over 6.4 million deaths worldwide. In a worldwide vaccination campaign that varies “widely”, approximately 60% of the global population has been vaccinated. However, vaccination rates are much lower that this in many places.
Although the available vaccines have been “highly successful” in reducing the effects of infection, variants are “continuously emerging” to render them “less and less effective”. Most are centred on responses to the Spike (S) protein. The paper identifies one approach to this problem as “redesigning and testing new vaccines” in response to circulating variants. This means essentially opting into a game of catch up against a virus, and current vaccines quickly become “obsolete”, says Dr Marcus Horwitz of UCLA. The researchers suggest that in order to tackle the pandemic “most effectively”, we really need “universal vaccines”.
“The optimal COVID-19 vaccines would be safe, potent, and affordable, as well as universal.”
The candidate in question
The researchers believes that their vaccine, which comprises a replicating bacterial vector expressing the SARS-CoV-2 membrane (M) and nucleocapsid (N) proteins, fulfils these criteria. They break down each criterion as follows.
Safety – the vaccine vector is a further attenuated version of a tularemia vaccine, which has been administered to “millions” of people.
Potency – two immunisations of the MN vaccine have been demonstrated to protect golden Syrian hamsters after “high-dose SARS-CoV-2 respiratory challenge”.
Affordability – the vaccine can be grown to “hundreds of millions of doses overnight” in a “simple broth culture”. Furthermore, after lyophilisation, it can be stored and transported at “refrigerator temperature”.
Universality – the MN vaccine is centred on inducing immunoprotective humoral and T cell responses to “highly conserved SARS-CoV-2 proteins”.
Another feature of the vaccine is capability for oral administration, which would address “two major factors hampering more all-inclusive vaccination”. The first is a lack of equipment and “trained personnel” to deliver injectable vaccines. The second is a “contributing, albeit difficult to quantitate” factor to vaccine hesitancy: feat of needles. This would be “rendered moot” by oral delivery.
The study
The study advances previous research to demonstrate the efficacy of this vaccine when administered orally, as opposed to intradermally or intranasally. The results suggest that it prevented against “severe weight loss” and protection was “at least as strong” as with other methods of administration. It also “significantly protected against lung pathology” and “significantly reduced the viral load in the oropharynx and lungs”.
The authors believe that their “highly demanding animal model” is a positive indication of the potential presented by their vaccine.
“This conveniently administered, easily manufactured, inexpensive, and readily stored and transported vaccine could play a major role in ending the COVID-19 pandemic by protecting immunised individuals from serious disease from current and future strains of SARS-CoV-2.”
Next steps
Dr Horwitz hopes that the vaccine will progress to manufacturing for oral administration through an acid-resistant enteric capsule. This would allow it to be safely released in the small intestine, and it could then be tested in humans.
“We also plan to expand the vaccine to protect against infections caused by other types of potentially pandemic coronaviruses such as the virus that causes Middle Eastern Respiratory Syndrome.”
This could be a helpful tool in our continued fight against the constantly evolving virus. Do you think an oral vaccine is the solution? Will it help us overcome elements of vaccine hesitancy?
For more on COVID-19 vaccine strategies at the World Vaccine Congress in Washington next month, get your tickets here.
On Friday 24th March 2023 the WHO and other organisations and individuals observe ‘World Tuberculosis Day’ with the theme “Yes! We can end TB!”. This uplifting and emphatic statement is intended to “inspire hope” and encourage action among leaders.
In particular, 2023 is a “critical” year, with opportunities for “visibility and political commitment” offered at the 2023 UN High-Level Meeting on TB. WHO’s “spotlight” for this year will be “urging countries to ramp up progress” as we get closer to this meeting. World TB Day is observed annually on 24th March as this marks the day in 1882 when the TB-causing bacterium was discovered.
What is TB and why are we still fighting?
TB is described by WHO as “one of the world’s deadliest infectious killers”, claiming the lives of “close to 4,400 people” every day. Caused by Mycobacterium tuberculosis, it most commonly affects the lungs and is spread from person to person through the air. Although TB is found across the globe, the largest number of new cases in 2021 occurred in the WHO South-East Asian Region, with 46% of new cases.
As TB is “preventable and curable”, efforts to this end have saved up to 74 million lives since 2000. However, we continue to experience devastating infections and deaths. Most recently, the COVID-19 pandemic has caused major disruptions to global efforts against other diseases, and this has combined with “conflicts” and “socioeconomic inequities” to undo years of progress. Indeed, WHO recently highlighted that “for the first time in over a decade, estimated TB incidence and deaths have increased”.
When we spoke to Dr Mark Feinberg about why this has happened, he offered an interesting insight into how we as humans respond to threats. He suggests that “if you have a problem and it’s there for a long time, and it’s hard to deal with, you tend to try and ignore it and put it in the back of your mind”. Dr Feinberg argues that for TB, as with other infectious diseases, media attention may have slipped but progress continues to be made by researchers.
Missing key goals
In an article in The Lancetin March 2023, authors Dr Tereza Kasaeva, Hannah Monica Dias, and Dr Madhukar Pai wrote about the importance of meeting the “ambitious targets” from previous UN meetings that have been missed.
For example, treatment goals were identified in 2018 for countries to treat an “additional 40 million” people with TB and provide preventative treatment to “at least 30 million people at risk” by 2022. However, between 2018 and 2021, 26.3 million were treated. This is “still far short of the 40 million. Furthermore, the number of people provided with preventative treatment was “12.5 million”, again “still far from the target”. Why is this?
Disruptions and devastation
The authors identify the “health-care disruptions due to the COVID-19 pandemic” as a key factor. In addition, conflicts and “widening socioeconomic and health inequities” have been “devastating” for TB care.
“As sobering as this news is, it is important to find hope and keep the fight going.”
Turning the TB tide
The paper does identify “reasons for optimism”. Through a combination of “high-level leadership, increased investments, faster uptake of new WHO recommendations and adoption of innovations, accelerated action, and multisectoral collaboration” the authors identify potential to “turn the tide” on TB.
“2023 will be a crucial year.”
As we continue to engage with lessons learnt through the COVID-19 pandemic, we can exploit the “remarkable investments” made across the countermeasure spectrum.
“It is time to develop and scale new vaccines for tuberculosis, and the case for investment is strong.”
The authors state that COVID-19 vaccine development platforms could be “leveraged and deployed” for TB vaccines to “enormous” effect.
Priorities for partners
The paper also offers ten priorities that require a “unified response across sectors and partners” to “fast-track the fight” against TB.
Enhancing high-level leadership and advocacy to prioritise ending tuberculosis driving down deaths and ending suffering.
Strengthening multisectoral engagement and accountability to address the upstream and wider health and social determinants of tuberculosis.
Urgently increasing funding for essential tuberculosis services, including the health workforce.
Substantially increasing investments in tuberculosis research to drive technological breakthroughs, such as vaccines and the rapid uptake of innovations.
Advancing universal health coverage and integration of efforts to end tuberculosis into primary health care to ensure all people with tuberculosis have access to affordable quality care while strengthening health systems and engaging all providers.
Addressing the drug-resistant tuberculosis crisis, with a focus on roll-out of WHO-recommended universal drug susceptibility testing and shorter, all-oral, injectable-free treatment to close persistent gaps in care.
Markedly scaling up provision of preventative treatment for tuberculosis, especially for household contacts.
Ensuring meaningful engagement of civil society, communities, and people affected by tuberculosis.
Promoting human rights and combating stigma and discrimination.
Aligning with the ongoing efforts on pandemic preparedness to proactively tackle future disruptions to tuberculosis services through key partnerships and collaborations for better efficiency and synergy, particularly at the country level.
“Although the COVID-19 pandemic has been a massive setback for progress in ending tuberculosis, it has shown us that nothing is impossible if we set our minds to it and make the necessary investments.”
“We must be bold enough to imagine a world where people with tuberculosis receive humane and quality care wherever they are and have access to the best tools we have and where tuberculosis finally gets the budget and political attention we need to end this great plague.”
We will hear more from experts like Dr Mark Feinberg on diseases that have been “neglected” during the COVID-19 pandemic at the World Vaccine Congress in Washington, so join us by getting your tickets here.
In a study published in Nature Communications in March 2023, researchers investigate the socioeconomic benefits of a set of “idealised” vaccine distribution scenarios in relation to COVID-19 vaccination programmes. Their results suggest that an equitable vaccine distribution could increase global economic benefits by $950 billion each year, compared to a scenario that ‘fully’ vaccinates vaccine-producing countries first. Lessons that should have been taken on from early pandemic vaccination strategies are emphasised in their evaluation of the multiple benefits of a more equitable approach.
COVID-19 vaccination
The authors note that the “recurrent waves” of SARS-CoV-2 variants have enabled the COVID-19 pandemic to threaten public and economic health across the globe for three years.
“Though vaccination has regionally mitigated the pandemic toll in certain areas, global inequities in vaccine distribution is an important issue which presently weakens the effectiveness of vaccines in lowering transmission globally.”
Despite efforts of many organisations to promote accessibility, such as the ACT Accelerator, the current levels of vaccination demonstrate that there are “still many disincentives for equitable vaccine distribution”.
“It is clear that nobody wins the race until everyone wins.”
Thus, the authors were motivated to consider the role of collaboration between countries that produce vaccines and other countries. To address the issues of disincentives and individual benefits, a “framework” to link epidemiological and socioeconomic modelling is required, to “probe the potential gains of global vaccine allocation strategies from the socioeconomic perspective”.
Benefits and consequences
The authors acknowledge that “local shortages of many commodities” across the world illustrate the importance of our “highly connected global supply chains”. This was demonstrated in the trickle down of negative economic effects from a country in lockdown to other countries along supply chains. The opposite is also true: “vaccination decisions in one country may be beneficial to the economic recovery of other countries, which is often referred to as one type of externality of vaccination”.
The study
In the study, the authors link epidemiological and socioeconomic modelling frameworks to “quantify the socioeconomic benefits of a set of idealised COVID-19 vaccine-distribution scenarios”. The evaluation considered three main outcomes:
The health gains
The lockdown-easing effect
The supply-chain rebuilding benefit
The researchers modelled three sets of scenarios into a tiered structure. “Tier Global” addresses the issue of the “cooperative attitude” of countries, while “Tier Domestic” address the issue of “how received vaccines are allocated within each destination country”. This approach provides “new information” to enable us to understand the “game” of vaccine distribution and facilitate global vaccine cooperation.
Equitable distribution brings benefits
The analysis conducted not only demonstrates the “potentially significant differences” in benefits achieved by each mode of distribution, but also reveals why equitable vaccine distribution, and the consequent global economic benefits, have “not been achieved”.
“The ‘equitable distribution’, in this study, is not a simple appeal, but a solution that makes economic sense.”
The authors emphasise that it is not a sacrificial approach, but a mutually beneficial mechanism. Despite this, they believe that a “bias” in the “player’s decision-making” is created by poorly quantified and considered benefits of economic recovery in comparison with health gains. The conclusion, however, is that a “multilateral benefit-sharing instrument should be developed” in time for “future pandemics”, in order to remove the disincentives for early and equitable vaccine distribution.
“Such an instrument would provide enormous global health and economic benefits in a sustainable manner.”
For more on the global vaccine distribution strategies at the World Vaccine Congress in Washington next month, get your tickets now.
In March 2023 the board of directors at CSPC Pharmaceutical Group Limited announced that the company’s COVID-19 mRNA vaccine has been included for emergency use in China for the prevention of COVID-19. This is the “first independently developed mRNA vaccine product in China” granted for emergency use, as reported by CSPC.
SYS6006
The vaccine, SYS6006, is an mRNA vaccine that covers the Omicron subvariant BA.5’s core mutation at the spike mutation positions. It was granted emergency clinical trial approval in April 2022, and has completed trials with over 5,500 participants to demonstrate safety, immunogenicity, and efficacy.
The statement from CSPC reports that SYS6006 “consistently induces specific T-cell immunity” against strains of SARS-CoV-2, with immunity sustained at “high levels for an extended period”.
“The Product adopts advanced technology with independent intellectual property rights, with the advantages of achieving higher production capacity, better process reproducibility, large-scale production, and scale-up more easily.”
Jumping into action
This inclusion comes at a time of regrowth for China following its stringent COVID-19 policy, the “zero COVID” approach. The New York Times suggests that it may be used to support efforts to “jump-start an economy that had been hurt” by among the “harshest COVID-19 restrictions in the world”. It also describes this vaccine as a “source of national pride” for the Communist Party leadership.
Although it is not clear when the vaccine will become available to the public, this announcement marks a step forward in enabling China to move forward from a complicated COVID-19 approach, particularly considering the leadership’s reluctance to accept externally developed mRNA vaccines.
If the quality of this vaccine can be proven to the people of China, perhaps greater headway can be made into establishing a more equal and effective vaccination trend across the population. Despite lack of clarity in reporting, we have learnt in the past of public reluctance due to confusion and mistrust.
We will hear much more about mRNA vaccine development efforts and applications at the World Vaccine Congress in Washington next month. If you would like to join us, get your tickets here.
Africa CDC has confirmed that the Ministry of Health of the Republic of Tanzania declared an outbreak of Marburg virus disease (MVD) on 21st March 2023. The outbreak has been reported in Bukoba district, Kagera region, in north-western Tanzania. So far, a total of 8 confirmed cases and 5 deaths have been announced.
MVD
Marburg is a highly infectious and highly fatal zoonotic haemorrhagic disease. Africa CDC describes that human-to-human transmission occurs through “direct contact with body fluids” from infected persons or contact with materials that have been contaminated with infectious fluids. As noted by the CDC, there is no licensed vaccine or approved treatment, but “supportive management improves survival”.
The situation in Tanzania
The cases in Tanzania presented with “fever, vomiting, and bleeding from different body orifices” according to Africa CDC. Samples collected were tested positive for MVD by PCR at the National Public Health Laboratory.
This is the first confirmed incidence of MVD in Tanzania, and the high population mobility within the region poses a risk of cross-border transmission to neighbouring countries: Uganda, Rwanda, and Burundi.
The Ministry of Health has reportedly deployed rapid response teams to support further investigations. 161 contacts have already been identified and are being monitored, with active case search, case management, and risk communication “ongoing” in affected areas. Africa CDC is also sending experts to support the local response. The importance of understanding the “cross-border context” of the outbreak has been emphasised. Tanzania is the second African Union Member State to report an active outbreak at the moment, after Equatorial Guinea declared an outbreak in February.
Dr Ahmed Ogwell Ouma, Acting Director of Africa CDC, highlighted the organisation’s commitment to supporting “Tanzania and her neighbours” to “arrest this outbreak as soon as possible”. He urged members of the public to “continue sharing information in a timely manner” to promote an “effective response”.
“These emerging and re-emerging infectious diseases are a sign that the health security of the continent needs to be strengthened to cope with the disease threats.”
We will hear more about current efforts to develop effective Marburg vaccines at the World Vaccine Congress in Washington next month. Join us by getting your tickets here.
In March 2023, Vaxxinity announced that the first subjects of a Phase I trial had been dosed. The trial of VXX-401 will evaluate the safety, tolerability, and immunogenicity of the investigational vaccine designed to lower low-density lipoprotein (LDL) cholesterol. This is a known contributing factor of heart disease, which remains the “leading cause of death globally”.
LDL and heart disease
Vaxxinity states that heart disease claims “over 18 million lives per year”. LDL cholesterol, also known as ‘bad’ cholesterol, is a leading factor in heart disease incidence. Although there are approved treatments to lower LDL, it continues to contribute to deaths.
Enter VXX-401
The investigational vaccine by Vaxxinity is designed to lower LDL levels by targeting proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9). Designed using Vaxxinity’s proprietary synthetic peptide vaccine platform, it is being developed for the treatment of hypercholesterolemia. The platform is designed to “harness the immune system to convert the body into its own natural ‘drug factory’, stimulating the production of antibodies”.
The vaccine is being tested in a multi-centre Phase I dose-escalation trial that aims to enrol 48 subjects between the ages of 18 and 75 years with LDL cholesterol between 2.59 and 4.89 mmol/L.
CEO of Vaxxinity, Mei Mei Hu, described this progress as an “exciting milestone” in the pursuit to “vaccinate the world against heart disease”. This goal includes an intention to keep the vaccine “convenient and accessible” in order to address an “unmet need”.
“With an LDL-lowering vaccine we can potentially offer an option that’s cost-effective, safe, convenient, long-acting, and deployable.”
Hu believes that the solution to the “problem of heart disease” will be a “scalable, accessible technology” that reaches the “hundreds of millions, if not billions of people at risk”. Professor Stephen Nicholls of Monash University and Victorian Heart Hospital in Australia is “excited” to get the “first-in-human trial” underway.
Professor Nicholls suggests that the “concept of a vaccine for cholesterol” could be a “game-changer in cardiovascular health”.
“Targeting PCSK9 with a monoclonal antibody is a proven and effective approach for lowering cholesterol and reducing the risk of heart attack and stroke. Despite the availability of statins and the approval of PCSK9-targeting medicines, there is still a need for new therapies.”
Previous data
Data from non-human primate studies demonstrate that VXX-401 was “well tolerated” and “provided durable and significant LDL reduction of 30% to 50% change from baseline”. They also prove strong immunogenicity and suggest that VXX-401 “may safely overcome immune tolerance”.
We look forward to hearing more from Vaxxinity’s Mei Mei Hu at the World Vaccine Congress in Washington next month! Join us by getting tickets here.
In March 2023, Vaccitech announced top-line interim data from a Phase Ib/II clinical trial of its VTP-200 vaccine in women with low-grade cervical human papillomavirus (HPV) lesions. The vaccine is intended to treat HPV infections, catching them before the virus causes high-grade lesions. The data was described as a “promising step” with more to come in early 2024.
HPV
Vaccitech states that an estimated 291 million women across the world are “carriers” of HPV DNA. Persistent genital HPV infection is “responsible for almost all cases of cervical pre-cancerous lesions”, which can lead to cervical carcinoma.
“Over 95% of cervical cancers are caused by HPV infection.”
WHO indicates that the two most common “high-risk” genotypes cause around 70% of all cervical cancerrs.
“HPV was estimated to cause almost half a million cases and 250,000 deaths from cervical cancer in 2002.”
Although there are two prophylactic vaccines against HPV, it continues to cause problems globally.
HPV001 and VTP-200
HPV001 is a fully-enrolled, randomised, placebo-controlled multi-centre trial to evaluate the safety, efficacy, and immunogenicity of VTP-200. The study consists of an “open label, non-randomised, dose escalation lead-in phase of 9 participants”. This is followed by a “blinded, randomised main phase of approximately 96 participants with high-risk HPV”.
VTP-200 is a “investigational heterologous prime boost immunotherapy” comprising an initial dose using the ChAdOx vector and a second dose using MVA. Both encode the same HPV antigens to elicit an immune response to HPV.
Promising data
Data from the first 58 women enrolled who reached their 6-month timepoint in the study were reviewed with the trial expected to continue as planned to the 12-month endpoint. Immunogenicity results showed “high responses”. This was defined by Vaccitech as an “average greater than 1,000 spot-forming units per million peripheral blood mononuclear cells in an ELISPOT assay”.
VTP-200 was “generally well-tolerated”. Bill Enright, CEO of Vaccitech, described the data as a “promising step in the right direction”, stating that he looks forward to final data next year”.
“Currently people with persistent HPV infection have no treatment options until they develop high grade lesions.”
Enright referred to repeat cervical screening without a treatment option as a “frustrating and anxiety-provoking” approach.
We look forward to hearing more from Vaccitech at the World Vaccine Congress in Washington. If you would like to join us, get your tickets here.
SpyBiotech, a biotechnology company spin out from the University of Oxford, announced in March 2023 that it had received a grant of $4,094,561 from the Bill & Melinda Gates Foundation to “further develop” its novel SpyVector platform. This platform technology targets infectious diseases, cancer, and chronic diseases. The project will “harness” SpyBiotech’s “plug and display” technology to create a broadly cross-protective coronavirus vaccine.
SpyVector
SpyBiotech describes SpyVector as a platform based on recombinant adenovirus that enables “easy and efficient covalent decoration of the surface of the adenovirus” with pathogen antigens. Furthermore, a recent publication demonstrated that it genetically encodes the antigen.
“The platform increases the quantity of antibodies induced by decorating the adenovirus with the antigen while maintaining the T cell response to the encoded antigen.”
SpyBiotech continues to develop this platform with Principal Scientist Dr Matthew Dicks and team. Dr Sumi Biswas, President and CEO of SpyBiotech, hopes the grant will “showcase” its potential for vaccines “against a wide range of pathogens and therapeutic applications”.
The platform is based on science developed at Oxford, using a proprietary protein “superglue technology”. This “minimises delivery risk and enhances immunogenicity and efficacy”. SpyBiotech suggests that the technology is “potentially one of the safesy and most effective way to create vaccines: cost-effective and highly scalable”.
It therefore has potential for infectious disease use in “challenging environments”, but also potential applications in non-infectious disease settings such as cancer.
With just weeks to go until the World Vaccine Congress in Washington this April, we are delighted to share another in our series of exclusive interviews with some of the fantastic speakers lined up for the event. This interview was a zoom conversation with Dr Niranjan Sardesai, founder, President, and CEO of Geneos Therapeutics. Our conversation explored the work that Dr Sardesai and his team and doing in developing personalised cancer vaccines, and how this interacts with research happening in the infectious disease area. A full transcript can be found at the bottom of the page. We hope you enjoy it!
Geneos at a glance
Our first question aims to provide a bit of context to Dr Sardesai’s work and his presence at the Congress. He describes Geneos as a “clinical stage immuno-oncology company” that is developing “exquisitely personalised cancer vaccines” based on its GT-Epic platform and importantly, one that is already seeing dramatic tumour reductions in clinical trials.
How does Geneos approach cancer vaccines?
Dr Sardesai uses the term “exquisitely personalised” in his previous answer, and we were curious about how Geneos is pursuing this goal. For Dr Sardesai, “these are really exciting times for the cancer vaccines field”. Although the understanding of the immune system’s response to tumours is “not a new finding”, the challenge has “always been” encouraging this in more patients.
The approach that Geneos is taking is a “holistic view”. The team wanted to identify the tumour-specific antigens, to develop the right immunity to those antigens, and to understand the “ideal clinical settings”. Thus, the concept of the personalised vaccine, “truly tumour derived from each patient”, was developed. The mutations in tumours are twofold; not only do they enable the cancer to “avoid the immune system”, but they can act as the “Achilles heel of the tumour”, marking the cells to the host immune system.
“So what we’re trying to do is exploit those differences in the cancer cell and because these differences are idiosyncratic, they’re different from each patient to patient. The products that are designed based on these differences necessarily have to be personalised.”
The “core” of the GT-Epic platform is understanding and identifying the unique makeup of each patient’s cancer cell, developing their personalised vaccine, and then treating the patient.
What challenges do these vaccines bring?
From the sounds of it, developing personalised cancer vaccines is not a simple process, so we asked for a bit of a rundown of some of the key challenges that Dr Sardesai and his team encounter. This is a “really fundamental question for the field”, says Dr Sardesai. He suggests that because the technology to identify changes in tumours has been developed through “tremendous improvements in sequencing capabilities”, we are in the “golden age of genomics and bioinformatics”. As such, “external developments” in the wider vaccine space are enabling solutions in the cancer vaccine arena.
“I feel like this is the right time and the right place for cancer vaccines, personalised cancer vaccines, because some of the key technological hurdles around identification have been addressed by the field as a whole. So we’re certainly grateful for that.”
However, for each patient there can be “hundreds of somatic changes”. Consequently, identifying “targetable neoantigens” presents another challenge. Among the community Dr Sardesai identifies “different methods” for identifying these, but for him and his team, the lesson they are taking forward is that “targeting more” of these neoantigens is “going to be preferable”.
“Geneos is taking the approach that we identify all targetable mutations, and we incorporate all of them into our tumour vaccines and let nature make the call.”
Dr Sardesai states that lessons from natural immunity show that the immune system is capable of “driving responses to a large range of immunogens” every day. Thus, the team at Geneos puts the “decision-making process” in the hands of the individual immune system. Another challenge is that “patients and the tumours are certainly not waiting around” for treatments to be developed.
“Speed is of the essence.”
Therefore, a challenge is keeping down the turnaround times from biopsy to treatment. With their DNA-based platform, Dr Sardesai and colleagues have already shrunk this to 6-8 weeks. However, they “know” they can do it in under 4 weeks. This is where a clinical development aspect comes into play, because “sometimes clinical development decisions are made based on the capabilities of the platform”. For example, if a platform has a long turnaround time, it may not be applicable to certain types of cancer or treatment settings.
“What Geneos has done is we’ve shown that we are treating patients with bulky tumours.
So far, results from the field are exciting, showing that personalised cancer vaccines can work in earlier stage cancers to “prevent recurrence.” Perhaps even more dramatic is that Geneos has shown that it can reduce – and even eradicate – bulky tumours and their metastases in patients with advanced cancer. These clinical results have led to the planning of a potentially registrational clinical trial.
Infectious diseases and cancer therapy
For many of our speakers who are not directly engaged in infectious disease research, the field has had implications for their work, whether in terms of COVID-19 disruptions or accelerated technological developments. We asked Dr Sardesai about the interplay between his work and infectious diseases. Interestingly, Dr Sardesai entered the field “from the infectious disease side” and he identifies a “phenomenal impact” on the approach he is taking to cancer vaccines.
A key similarity is the notion of central tolerance. Simply put, years (and years) of evolution have developed an immune system capable of “identifying what is self from foreign”. Although we do experience certain auto-immune diseases, in general, the immune system is fairly confident in making these distinctions. This has been “exploited fundamentally” in infectious disease research, and the cancer field can learn from this by seeing the link between “what is it that drives immunity” and tailoring the immunity to the pathogen.
In cancer, the tumour neoantigens are “non-self”, so Dr Sardesai suggests that “just as we think of viral antigens and bacterial antigens as foreign”, these neoantigens can be perceived as “foreign”. However, for infectious diseases the aim is usually prevention, and in Dr Sardesai’s work the goal is therapy.
As he identifies lessons he has learnt from infectious diseases, Dr Sardesai also hopes to share insights the other way. For example, with recent COVID-19 vaccines, they were “very, very effective” in terms of antibody responses, but “it’s been challenging to do clearance because of lack of T cell immunity”.
“So what we love about the idea is that I think we started out from the infectious disease, we all learnt a lot, what we learnt through developing cancer vaccines is what drives effective cellular immunity, which can then go back into developing better infectious disease vaccines.”
We also like the idea of interaction between the different areas of vaccine development, and this leads us nicely into our final question!
Why the World Vaccine Congress?
We love to understand more from our speakers when it comes to what brings them to the Congress. Dr Sardesai puts it perfectly when he says that it’s been organised to cover “all things vaccines”! This means that “concurrent sessions” will cover every aspect of vaccine development and deployment. In particular, he’s looking forward to the regulatory tracks because “these developments that are going on are happening in real time”.
“I’m looking forward to…being able to interact with colleagues across different silos.”
We really enjoyed this conversation with Dr Sardesai and hope you did too. If you would like to hear more on his work, join us at the World Vaccine Congress this April. To read the full transcript, see below!
In March 2023, RVAC Medicines and the University of Pennsylvania (Penn) announced a collaboration to pursue the development of mRNA vaccines to “modulate the body’s normal immune response as possible treatments” for “certain autoimmune diseases and allergic conditions”. The focus will be on potential vaccines for food allergies and selected autoimmune indications.
Unmet medical needs
A statement from RVAC indicates that autoimmune diseases and allergic reactions or conditions comprise “rising unmet needs” that require “more treatment options” for patients across the globe. Autoimmune diseases occur when the immune system becomes “oversensitive” to harmless proteins and triggers an attack on the body itself.
The US NIH “more than 80 autoimmune diseases”, some of which are well known, and others that are “rare and difficult to diagnose”. Many have “no cure”. RVAC suggests that these diseases have “risen steadily in recent years”. Indeed, an average annual increase of 3% to 9% represents a “growing global health concern”. Allergic reactions or conditions are caused by the immune system being triggered against a “harmless allergen” such as foods or animals.
Addressing these needs
In response to the needs identified above, Dr Drew Weissman of the Perelman School of Medicine at Penn is bringing his team to a collaboration with RVAC to “develop and optimise mRNA vaccine candidates”. The goal is to “induce immune tolerance, thereby reducing the chances of autoimmune responses”.
Dr Weissman describes allergic reactions and “inappropriate autoimmune responses” as “difficult and restrictive” conditions in people’s lives.
“We are excited to begin this collaboration for certain conditions that currently have imperfect and incomplete therapies.”
Dr Sean Fu, CEO of RVAC, is also excited, calling Dr Weissman a “pioneer in the field”.
“With this collaboration, we want to develop mRNA vaccine product candidates with the potential to improve lives of patients who suffer from certain autoimmune diseases and allergies.”
Dr Jason Zhang is RVAC’s Chief Scientific Officer and is “very glad” to work with Dr Weissman for a “broad spectrum” of conditions.
“This collaboration will apply the mRNA technologies to induce antigen-specific immune tolerances, and RVAC is committed to becoming a leader in this field.”
For more detail on the myriad possibilities presented by mRNA approaches, join us at the World Vaccine Congress in Washington this April. Dr Drew Weissman and his lab have been shortlisted for a VIE award at the Congress. To view the lists for each category click here!
In March 2023 new metagenomics data and SARS-CoV-2 sequences appeared on GISAID (the Global Initiative for Sharing Avian Influenza Data) and were available to researchers across the world for a short period of time. Although access was restricted to allow further updates, WHO was notified of this data and later learnt that they are the basis for an update to a paper that is being re-submitted to Nature by China CDC.
A statement from WHO in March indicated that discussions between WHO, SAGO, and China CDC, with participation from “some of those who had accessed the data”, enabled the organisations to “gauge the significance of this data and the analyses of this data”.
New data, new ideas
WHO suggests that the presentations from China CDC and “invited international researchers” identified newly available data from the Huanan Seafood Wholesale Market. This included metagenomic data of environmental samples from stalls and wastewater collection sites from as early as January 2020.
Not only were SARS-CoV-2 sequences available, but “mitochondrial DNA of several animal species” and human DNA. Among the animal species, DNA from “wild raccoon dogs, Malaysian porcupine, and bamboo rats” were included in “SARS-CoV-2 positive environmental samples”. WHO believes that these findings demonstrate the presence of animals at the market “shortly before the market had been cleared” on the 1st of January 2020 during public health measures.
“These results provide potential leads to identifying intermediate hosts of SARS-CoV-2 and potential sources of human infections in the market.”
WHO refers to a pre-print by Liu et al, 2022, which indicates that raccoon dogs were not among the animals tested in early 2020. However, the presence of “high levels of raccoon dog mitochondrial DNA” in this data does indicate that raccoon dogs and other animals may have been present at the market before it was cleaned.
SAGO encourages sharing
SAGO states that it will continue to evaluate “any and all” scientific data that are shared by researchers from “anywhere in the world”.
“SAGO encourages any and all data related to the studying of the origins of SARS-CoV-2 be made available immediately for robust and comprehensive review.”
Although previously accused of neglecting the investigations into the origins of the COVID-19 pandemic, SAGO continues to “strongly” recommend that researchers in China investigate the “upstream sources of the animals and animal products present” at the Huanan market before its closure in January 2020. As Dr Mike Ryan emphasised in a WHO briefing in February 2023, WHO relies on Member States’ independent research to be shared with the global scientific community.
For more on SARS-CoV-2 data and vaccine development, join us at the World Vaccine Congress in Washington next month.
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