In September 2023 the University of Birmingham shared that the Bacterial Vaccines Network (BactiVac) was awarded £1.4 million by the UK government. This funding is intended to “accelerate” the development of bacterial vaccines to prevent infections and is part of the “global fight” against AMR (antimicrobial resistance). Bacterial vaccines can prevent the need for antimicrobials and prevent infections from developing at all.
GAMRIF
The Global AMR Innovation Fund (GAMRIF) within the Department of Health and Social Care is a UK aid fund that supports “early-stage innovative research” in “underfunded areas” of AMR research and development with expected benefits for people in LMICs. Collaborating with research organisations, governments, and industry, GAMRIF aims to:
Establish international research partnerships and support research competitions that fund innovation and development of new technologies to tackle AMR
Leverage investment from other partners and donors to support sustainable financing for AMR
Establish global research partnerships using a One Health approach
Fund projects that will develop solutions specifically for LMICs
Further funding
The University of Birmingham suggests that the latest funding furthers an initial £1.4 million award in 2019. Both awards are part of the UK’s 20-year vision and 5-year AMR national action plan. It will enable BactiVac to “continue diversifying the current pipeline of vaccine development projects” and “increase collaborations” between researchers in LMICs and the UK. It also supports Network activities aimed at “enabling the equity of access” for LMIC members.
Synergistic progress
Professor Calman MacLennan is Director of BactiVac and “extremely grateful” to partner with GAMRIF.
“There is clear synergy between our organisations and the support provided by GAMRIF is vital for delivering BactiVac’s objective of advancing vaccines against bacterial pathogens and AMR.”
Professor Adam Cunningham, Co-Director of BactiVac and Professor of Functional Immunity stated that GAMRIF “supports strategies to tackle AMR” and “bacterial vaccines play a key role in this”.
“The partnership between GAMRIF and BactiVac is so important for controlling AMR.”
Professor Dame Sally Davies, UK’s Special Envoy on AMR, is “absolutely delighted” by the partnership.
“By advancing bacterial vaccines, the Network plays a key role in the global fight against antimicrobial resistance.”
In September 2023 Gavi announced the publication of its 2022 Annual Progress Report, which presents insights into a “year of recovery” for immunisation services thanks to “historic levels of investment” by lower-income countries. Just a few months ago the organisation celebrated the immunisation of over 1 billion children, a milestone that is highlighted in the report. Here we investigate the key themes and concerns of the report.
The Chair and CEO weigh in
Professor José Manuel Barroso, Chair of the Gavi Board, and CEO David Marlow open the publication by reflecting on the findings of the report and the goals it presents. They recognise that “nearly half of lower-income countries have recovered to or are above pre-pandemic DTP3 coverage levels”. This is a standard that refers to immunisations with the third dose of diphtheria, pertussis, and tetanus-containing vaccines. However, “some countries saw slower progress”.
Although the number of so-called “zero-dose children” has fallen from 12.4 million to 10.2 million, this is higher than the estimated 9 million of 2019, with a reduction of 34% required to meet the target for 2025.
“As we reflect on the important progress and urgent challenges that remain, the Vaccine Alliance nonetheless acknowledges the tremendous effort countries have made to get routine immunisation back on track.”
Professor Barroso and Mr Marlow recognise that 2022 was “indeed complex and challenging for global health”; COVID-19 caused great suffering and undermined routine immunisations. Polio and diphtheria emerged in some countries for the first time in “decades”, Uganda “battled an outbreak of Sudan ebolavirus”, and mpox was declared a PHEIC. Thus, 2023 was “heralded” as a Year of Renewal.
In December 2022, the Gavi Board approved “Gavi 5.1”, an “evolution” of the 5-year programme strategy with renewed focus on essential and COVID-19 vaccinations, reaching zero-dose children, introducing new vaccines, and strengthening the Alliance’s role in PPPR: pandemic prevention, preparedness, and response.
“To make up the ground we lost during the pandemic, in December 2022 the Gavi Board approved a more than $600 million investment to protect 86 million girls [with HPV vaccines] by 2025.”
With “climate change, deforestation, and migration” come increased risks of infectious disease outbreaks. This has been demonstrated in the “tragic turn” of cholera cases increasing globally. As these risks increase, the importance of Gavi’s commitment to vaccine equity is emphasised. An example of how vaccine equity is challenges it the “dearth of vaccine manufacturing in some regions”, such as across Africa. Gavi recognises its responsibility to “build healthier vaccine markets” by working with African countries and Africa CDC, establishing a greater manufacturing capacity in Africa.
The foreword concludes with a reflection on the “six core values” that guide Gavi’s work: teamwork, respect, openness, accountability, innovation, and country-driven.
Leaving no one behind
Gavi’s “vision” is “leaving no one behind with immunisation”, which translates into the mission: “to save lives and protect people’s health by increasing equitable and sustainable use of vaccines”. This mission is supported with four strategic goals (below) with strategy indicators.
The vaccine goal
The report confirms that since 2000, Gavi has helped countries reach over 1 billion unique children with routine immunisation. It also highlights a range of other achievements, including the interesting fact that “children in Gavi-supported countries are better protected than children in other countries” due to the “breadth of protection” by vaccines in the Gavi portfolio. The growth of this portfolio is illustrated in the figure below:
The other goals are explored through graphics and figures throughout the report, and we encourage you to access it here if you are interested!
Learning from the report
What can we take from the facts, figures, and findings of the report? Marlow emphasises that the data show that “immunisation really is a global success story in terms of the unprecedented levels of collaboration”.
“At the same time, we must not lose sight of the challenges ahead, as countries face a very uncertain future as a result of deteriorating economic conditions, an uncertain geopolitical outlook, and the impact of climate change among other factors. The need for continued collaboration and innovation, today, is greater than ever.”
Professor Barroso comments that the Alliance’s “priority” is to help countries “maintain this trajectory” of restoring immunisation, broadening coverage, and mobilising domestic resources.
“The prospect for immunisation to deliver transformative societal and economic benefits is greater than ever, but only if we are collectively able to navigate the path ahead.”
WHO Director-General Dr Tedros Adhanom Ghebreyesus is encouraged by the “global rebound” in immunisation, which he describes as a “tribute” to those who have worked on it.
“But global and regional averages don’t tell the whole story, and they mask severe and persistent inequities. When countries and regions lag, children pay the price.”
He is “proud to work with Gavi” to ensure that every child “benefits from the life-saving power of vaccines”. UNICEF Executive Director Catherine Russell agrees that “the job isn’t done yet”, with many countries “yet to recover the ground they lost during the pandemic”.
“We must double down on our efforts to reach every child. The recovery has started, now let’s make sure it’s equitable and durable.”
If you’ve read the report, what do think it means for the global vaccine community? How can Gavi-supported countries continue to recover, and what are the implications for countries that don’t receive support from Gavi?
In September 2023 CEPI announced a “renewed collaboration” with Global Affairs Canada, comprising CAD 1 million in funding to “accelerate the development of vaccines against emerging infectious disease”. The funding will support CEPI’s efforts to “manage the inherent biological security risks” of the century, encourage engagement with the security community, and “catalyse new and stronger health partnerships”. This collaboration also furthers progress on the 100 Days Mission.
“As stewards of global public funds CEPI has a critical responsibility to ensure that CEPI-funded R&D is conducted safely and securely.”
Weapons Threat Reduction
CEPI reports that Global Affairs Canada’s Weapons Threat Reduction Programme (WTRP) is going to support the development and implementation of CEPI’s biosecurity strategy. Heading this up is inaugural Director of Biosecurity, Dr Andrew Hebbeler. Dr Hebbeler is a “globally recognised biosecurity expert” with experience leading “global policy and capacity-building efforts aimed at preventing, detecting, and responding to” biological events. These include natural, accidental, and deliberate events.
To identify relevant initiatives within the sector, CEPI intends to “map the biosecurity landscape” and its “intersection with global health and health-security spaces”. From there the organisation hopes to understand how it can offer “opportunities for alignment and collaboration”.
Trevor Smith, Canada’s Investor Council Representative, commented that the WTRP “recognises the critical role” of vaccines and medical countermeasures in the “fight against the deliberate use of disease”. The programme has been investing in CEPI’s “world-leading R&D since 2017.
“We are proud to build on and further strengthen our collaborative partnership with CEPI through this biosecurity-focused contribution. In the global campaign to prevent, detect, and respond to biological health threats and to build sustainable health-security capacity, multi-sectoral cooperation is imperative.”
Biosecurity meets health
The 100 Days Mission “directly contributes” to health and security goals by contributing to pandemic prevention, regardless of an outbreak’s origin.
“It is imperative that CEPI define the risks and opportunities underpinning expanded investments in the development of safe and effective vaccines and other biologic countermeasures.”
Thus, CEPI can assume a “leadership role”, driving international norms and standards.
Lessons from COVID-19
In CEPI’s announcement in September we are reminded of the “devastating and destabilising effect” that infectious diseases have on society. COVID-19 had consequences for health, economies, and global security. Unfortunately, the risk of emerging infectious diseases is “increasing” thanks to a plethora of moving parts including climate change, urbanisation, and environmental degradation.
Technology troubles
Although emerging technology is exciting, creating “new and promising opportunities” to improve health, it also brings “new and evolving risks”. For example, as we explored in our summary of the Brown School of Public Health’s New Species of Trouble, there will be future outbreaks that may be triggered by accidental or deliberate pathogen release, as well as emerging technologies.
“Addressing biosecurity is a key component of strengthening global health security, and ensuring the world is prepared for future epidemics and pandemics.”
Dr Richard Hatchett, CEPI’s CEO, believes it is “vital” for countries to be ready to respond to biological threats “no matter the source or cause”.
“Investing in the ability to rapidly develop and manufacture vaccines and other biologic countermeasures against a broad range of potentially dangerous pathogens enables governments to advance their security interests at home and abroad.”
Dr Hatchett is “pleased to elevate the role of biosecurity in CEPI’s mission” and looks forward to the strengthened collaboration with Global Affairs Canada.
We know from before and during the COVID-19 pandemic that Africa’s demand for vaccines exceeds its local supply: 99% of vaccines administered on the continent are imported. The pandemic highlighted an existing need, but did it also galvanise action to establish greater “local” manufacturing? A recent report by Africa CDC, the Clinton Health Access Initiative (CHAI), and PATH, examines “current and planned vaccine manufacturing in Africa”. Here we look at the findings and recommendations presented in the report.
Why does Africa need manufacturing?
Apart from the pressures placed on Africa during the COVID-19 pandemic, Chatham House suggested in 2022 that “seven of every ten vaccines” used in Africa are donated by Gavi. A year before that, WHO Africa reported on the “enormous challenges” to establishing sustainable vaccine industries. The imbalance in production contributes to “unequal access” and “enormous health disparities” suggests this latest report.
In the report, Africa CDC, CHAI, and PATH analyse the current and planned manufacturing capacity in Africa, at a time of expected growth. The hope is that the paper will offer “insights into what is needed to develop a robust and sustainable vaccine manufacturing ecosystem”.
The process behind the paper
Although Africa needs a more effective vaccine manufacturing ecosystem, current capabilities are set to “expand dramatically” because of the COVID-19 pandemic. This highlight inequities and provoked a “surge in local political support for vaccine production”. So, what does the environment currently look like, and what might it turn into in the future? To answer these questions, a collaborative team engaged vaccine manufacturers across Africa between December 2022 and March 2023 on “current and planned production capacity, technical and commercial capabilities, and supporting functions”.
19 manufacturers were engaged in total, including manufacturers with commercial scale production capacity and early-stage projects. The team also involved a “variety of originator companies” outside Africa that are interested in technology transfers. The goal of this involvement was to identify their perceived “opportunities, challenges, and considerations for collaboration”.
The “benchmark” for vaccine demand was 2030, but 2040 is also considered in line with PAVM Framework for Action, which “sets the goal of manufacturing 60% of Africa’s routine immunisation needs on the continent by 2040”. The authors note that “other aspects of the vaccine manufacturing ecosystem” such as infrastructure development and improvement, regulatory authority strengthening, and market shaping, are not covered in the paper.
Finding 1: too much form/fill/finish not enough antigen production
The first finding in the paper identifies an “excess” of form/fill/finish” in contrast with a “dearth of antigen production”. The analysis explored two critical steps in the manufacturing process:
Drug substance production – the most cost-intensive and technically challenging step
Drug product production – including formulation, fill, and finish (form/fill/finish)
The authors suggest that “current capacity”, including ordered capacity, to form/fill/finish vaccines with imported antigen is “around 2 billion doses”. This “far exceeds” the average annual demand of 1.3 billion doses, yet further capacity is planned to increase production by “2 billion-plus doses”.
“The scale of overcapacity means there is a risk not every manufacturing project will be sustainable.”
On the other hand, antigen production capacity is “very limited” and “well below” the capacity required for PAVM’s domestic production targets. Furthermore, a significant proportion of antigen production is now used for non-vaccine products. Unfortunately, plans to expand manufacturing are “not enough to close the gap between production and demand”.
Finding 2: limited access to technology transfer
“Africa is reliant on technology transfers…due to the complex nature of vaccine manufacturing and the urgency with which manufacturers needed to scale production on the continent.”
At present, the research team identified “limited technology transfers”, which mean that African vaccine manufacturers may only be able to produce a “fraction of what they theoretically could”. They note that “technology transfer can be an important step in developing capacity to produce antigens locally”. Furthermore, “uncertain demand commitments” from governments for African-made vaccines add a complication.
“Demand uncertainty creates a barrier for African vaccine manufacturers…even among those manufacturers that have been able to sign agreements, unclear demand is delaying implementation of those transfers.”
Finally, a “single vaccine manufacturer” drives most current technology transfers to Africa. Thus, a “significant dependence” is established, making the “ecosystem vulnerable”.
Finding 3: available capacity does not equal commercial success
Although African manufacturers have “potential”, this does not guarantee “commercial success”. For example, despite “strong financial capabilities” for many manufacturers, commercial capabilities must be developed.
“Success depends on commercial savvy, market access, and effective partnerships, among other important factors.”
However, the “biggest obstacles” to the development of sustainable vaccine manufacturing capacity are “market access and demand materialisation”. Going global is easier intended than realised, and the report recognises “challenges breaking into the regional and global markets”.
“Local government support has been a driving force behind many manufacturers’ plans, but it has also led to strategies that are aligned to local political decisions rather than global market requirements.”
Recommendations and next steps
As is often the case, the importance of “investor and donor support” is raised as “crucial to a healthy and sustainable vaccine manufacturing ecosystem”. However, “careful consideration” must be given to how each investment supports “the whole” and pandemic preparedness. Similarly, stakeholders in Africa should “focus on efforts that build the continental vaccine manufacturing ecosystem” over “efforts that only benefit a particular manufacturer or country”.
Investors and donors should…
Reconsider investments in form/fill/finish capacity building in favour of efforts that strengthen commercial viability
Strengthen end-to-end manufacturing capabilities with investments that build capacity to manufacture antigens locally
Fund technical support to achieve international standards for Good Manufacturing Practice and prepare for/secure WHO prequalification
African manufacturers and governments should…
Improve the likelihood that investments have the right effect by strengthening commercial strategies and business planning, determining a clear pathway to market access
Diversify technology transfer partners to mitigate the risk of a market monopoly for antigen production
Be more precise in demand commitments for African-made vaccines, to catalyse technology transfers and create a market
These steps are a “multi-year, complex undertaking” and will require collaborative efforts. Thus, each of the partners outlines specific areas of commitment.
PATH – working with partners to determine the conditions needed to achieve the planned capacity, referred to as “future state mapping”.
CHAI – working with key stakeholders to develop a set of high-impact, market-shaping interventions and support in their execution, including addressing the strategic and commercial gaps identified through the landscaping exercise.
Africa CDC – working with African Union Member States to agenda-set activities guided by the PAVM Framework for Action by developing initiatives to support the procurement of African-made vaccines.
Do you agree with the findings and recommendations set out in the report? If you are based in Africa, how realistic is this? If you are in other areas, what lessons can you learn from this perspective?
Although insufficient attention has been directed towards the effects of vaccination on menstrual experiences, a study published in Science Advances in September 2023 presents research into the link between COVID-19 vaccination and “unexpected vaginal bleeding” in “nonmenstruating women”. The study, carried out in Norway, examines self-reported data from 2021 after spontaneous reporting systems revealed an increase in “menstrual disturbances” and “post-menopausal bleeding” (PMB).
Who was affected?
The study involved almost 22,000 participants and examined three main areas:
Vaginal bleeding in postmenopausal women
Unexpected vaginal bleeding in perimenopausal women
Breakthrough bleeding in nonmenstruating premenopausal women
The latter group involves a “substantial proportion of the female population” that does not menstruate because they use long-term hormonal contraception.
“While an altered bleeding pattern after COVID-19 vaccination has been frequently addressed among menstruating women, few studies have investigated such experiences in women who do not menstruate due to hormonal contraception.”
This figure (below) from the paper presents the data cleaning and inclusion process involved:
What did the team find?
Study author Kristine Blix told Nature that the results were “surprising”: 252 postmenopausal women, 1,008 perimenopausal women, and 924 premenopausal women report instances of unexpected vaginal bleeding. Of these experiences, around 50% were reported within 28 of vaccination. In postmenopausal women, the risk of vaginal bleeding “was increased two to threefold in the 4 weeks after vaccination”, compared to the pre-vaccination period. By comparison, the association with vaccination was “slightly stronger” in peri- and pre-menopausal women; the risk was increased three to fivefold.
Blix states that the “most important contribution” of their research could be that “female bleeding patterns are included as end points, or monitored, in clinical trials of new vaccines”.
Why this is important
Dr Kate Clancy from the University of Illinois told Nature that unexpected bleeding after menopause is “often very concerning”, but this link could allow health providers to “put their bleeding incidence into context’. However, she’s “so glad” to see attention on a “very underserved group”.
“Hooray for another group looking at peri- and postmenopausal people!”
In September 2023 Gritstone bio announced that is has been awarded a contract by BARDA to conduct a Phase IIb comparative study that will evaluate the company’s self-amplifying mRNA (samRNA) vaccine candidate, targeting COVID-19. The agreement is valued at up to $433 million and is part of the US HHS initiative ‘Project NextGen’. This aims to “leverage public-private partnerships” in pursuit of new vaccines and therapeutics for COVID-19.
The study
The contract will support Gritstone as it conducts a 10,000 participant, randomised Phase IIb double-blinded study. The study will compare the efficacy, safety, and immunogenicity of the company’s next-generation COVID-19 vaccine candidate with an approved vaccine. Gritstone reports that “preparations for the study are underway”, with the execution being “fully funded by BARDA”. It will take place in the US, in collaboration with the COVID-19 Prevention Network (CoVPN), which is a NIAID-supported network of trial sites based at Fred Hutchinson Cancer Centre.
samRNA
Gritstone explains that self-amplifying mRNA (samRNA) is “rapidly emerging” as a “well-tolerated, scalable, and widely applicable platform technology”. It can be used in multiple vaccines if the sequence of the antigen that is encoded in the vector RNA is changed. Like “traditional mRNA vaccines”, these vaccines use the host cell’s translation system to “convert mRNA” to protein target antigens, stimulating immunity. However, in contrast to traditional mRNA, samRNA “creates multiple copies of the antigen RNA once in the cell”, which is believed to be a possible factor in extending the “duration and magnitude of antigen expression”.
The CORAL programme
Gritstone’s CORAL programme applies the team’s infectious disease approach to the prevention of COVID-19, aiming to drive both B cell and T cell immunity using self-amplifying mRNA (samRNA) and novel immunogens containing Spike and additional viral targets. So far, the programme has involved three Phase I trials. It is supported by BARDA, NIAID, CEPI, and the Gates Foundation.
Dr Andrew Allen, Co-founder, President, and CEO of Gritstone bio is “honoured” to receive the award, which provides “strong validation” of the innovative vaccine platform in infectious diseases.
“Not only does this contract supply the necessary resources to advance the development of CORAL, but it also signifies the trust and confidence the US government has placed in our novel vaccine approach.”
Dr Allen recognised the “great utility” of first-generation COVID-19 vaccines during “the height of the pandemic”. However, they are “limited in breadth and durability of clinical protection”. Thus, CORAL was designed to “address these limitations”. In “multiple Phase I studies” the vaccine has demonstrated “induction of potent immune responses with potential to drive broad and durable clinical protection”.
“We are excited about this opportunity to work alongside BARDA and look forward to initiating the Phase IIb study in the first quarter of 2024…Gritstone now sits at the precipice of unlocking the full potential of our novel vaccine platforms in both oncology and infectious diseases.”
In September 2023 Revital Healthcare announced a “historic milestone in African manufacturing excellence”. The company was awarded Pre-Qualification (PQ) status by WHO in July 2023 for its early activation auto-disable (AD) syringe in Africa. This marks more than 10 years of commitment to injection safety in immunisation programming across Africa.
Early activation
The early activation feature is described as the “gold standard for safety in immunisation programmes”. It disables the syringe at the start of administration and injection. These devices have caused a substantial reduction in rates of blood-borne infections like HIV in immunisation programmes across Africa.
A milestone to celebrate
Although 8 manufacturers have WHO PQ status for the product, Revital is the “first and only” that is produced in Africa. This is expected to decrease average syringe transport times by up to 90%. Director of Marketing and Sales for Revital is Roneek Vora, who comments on the “historic” prequalification. This “exemplifies the transformative power of African innovation and manufacturing excellence”.
“Our commitment to the well-being of fellow people, especially children receiving life-saving immunisation, is our motivation to continue to progress.”
Gates Foundation support
Revital suggests that it will be able to produce “upwards of 300 million AD syringes every year”. This is supported by a grant from the Bill and Melinda Gates Foundation. Not only does the grant contribute towards the development of the product, but it created more than 200 local jobs in Kilifi County. Of these new roles, 80% have been assumed by women in “support of a joint commitment to gender equality”.
Violaine Mitchell, Director of Immunisation at the Gates Foundation, is “proud to support Revital’s efforts” to “sustainably expand the supply of these syringes”.
“As the first African manufacturer to be approved by WHO to produce early activation auto-disable syringes, Revital is paving the way to expand local production of syringes.”
In September 2023 WHO shared Considerations for developing a national genomic surveillance strategy or action plan for pathogens with pandemic and epidemic potential to support countries in the development of genomic surveillance strategies. This publication seeks to answer some questions that arise in the wake of surveillance gains from the pandemic, which highlighted the importance of genomics in public health toolkits. The guide establishes key considerations and an approach for developing a national strategy, and WHO recommends that all stakeholders can use it.
Developing an effective health toolkit
The introduction reflects that genomic surveillance has become a “priority” in public health systems, with genomic sequencing being used to characterise pathogens and monitor important public health priorities.
“The decrease in cost and time of sequencing and the exponential development of bioinformatic pipelines have played a critical role in integrating pathogen genomics into routine public health surveillance.”
During the COVID-19 pandemic, sequencing was emphasised as a useful tool in infectious disease surveillance, facilitating “earlier detection, more accurate investigation of outbreaks, closer real-time monitoring of pathogen evolution, and tailored development and evaluation of interventions”. Despite the importance of genomic sequencing, WHO identifies a need to “coordinate efforts, leverage and link existing surveillance and laboratory networks and capabilities, and systematically integrate genetic sequence data with clinical and epidemiological data”.
In the spring of 2022 WHO launched a 10-year global genomic surveillance strategy for pathogens with pandemic and epidemic potential. The goal is to “strengthen and scale up” genomic surveillance to promote “quality, timely, and appropriate” actions. Furthermore, WHO developed 13 “foundational principles” to encourage global data sharing:
Capacity development
Collaboration and cooperation
High-quality, reproducible data
Global and regional representativeness
Timeliness
Acknowledgment and intellectual credit
Equitable access to health technologies as a benefit
As open as possible, and as closed as necessary
Interoperability and relevance for national, regional, and global decision-makers
Trustworthiness and ease of use
Transparency
Consistency with applicable law and ethical regulations
Compliance and enforcement
Challenges and opportunities
The report recognises “considerable” challenges and opportunities in terms of infrastructure, capacity and capability requirements, and “harmonisation across systems”. However, these vary depending on the national context. Thus, an “adequately resourced” strategy will enable countries to set goals, objectives, and priority strategic actions.
The tool outlines key considerations and a stepwise approach, recommending that a national strategy should reflect the stages of the genomic surveillance value chain:
Key considerations
The guide suggests 5 “considerations” to inform strategy development:
Ensure strong national leadership, financial commitment, and governance framework
Focus on public health decision-making
Target all relevant pathogens with priority pathogen use cases
Strengthen data management
Promote data sharing and collaboration
Stepwise approach
Alongside the key considerations, the guide offers seven key steps with proposed actions for direct implementation. The duration and chronology, it suggests, can be adapted to national contexts.
How do you think this guide can be used in your region?
We look forward to hearing more on surveillance in the context of pandemic preparedness and prevention at the Congress in Barcelona next month. Are you joining us there?
In the last few weeks before the World Vaccine Congress in Barcelona, our start-up zone is reaching capacity! This week we are pleased to present another set of organisations that have already secured their spaces in the zone. To see previous introductions head over to our technology section.
Why be a start-up at the World Vaccine Congress?
Start-ups whose applications are successful are entitled to several unique benefits, including exhibition wall space, 2 complimentary passes, and marketing materials. For the first time at this event, there is the opportunity to participate in a 5-minute pitch during lunch breaks, an exciting way of introducing yourselves to colleagues and potential partners.
Our wonderful start-up manager, Isabella Aung, will receive your application and guide you through the process. She is looking forward to hearing more from interested companies, so do get in touch with her here via email (isabella.aung@terrapinn.com) or head straight to the application page here.
“I am super excited to connect with and welcome even more start-ups to our start-up zone at our Congress this October! It’s going to be our biggest and most exciting start-up zone yet!”
Introducing…
AilseVax
Developing new approaches for the development of cancer vaccines that have broad applicability to specific patient populations, in contrast with other vaccine approaches, through which bespoke cancer vaccines are developed for individual patients, a costly and time-consuming practice.
The core technology of AilseVax is the AltRNA8V™ antigen discovery engine, which aims to exploit the untapped antigenic potential encoded in tumour-specific mRNAs. To enhance the immunogenicity of new cancer antigens identified from the platform (and indeed other cancer and non-cancer antigens), the team has developed an exciting new approach to enhance antigen presentation.
ASET™ (Antigen to Surface Enhancement Technology) is an antigen presentation boosting technology that is adapted specifically for RNA-based vaccines.
BlokBio
Building a genomics intelligence platform for the next generation of BioTech. The platform simplifies complex genomics data analysis, making it accessible across your organisation regardless of technical experience.
Integrating the workflows alongside clients’ teams, they centralise and unlock value within genomics data.
The goal is to reduce processing time so clients can focus on high-impact work; a modular approach allows them to rapidly customise workflows tailored to your needs.
Founded to foster understanding and collaboration between data and people. They believe bringing clarity and understanding to complex genomics is key to accelerating discovery.
GEG Tech
The mission is to design safe and powerful innovations deriving from genetic engineering. The team has designed a new generation of nanoparticles combining the advantages of the LNPs and the viral vectors. These generations are constituted by viral packaging enabling good efficacy and stability, containing non-viral RNA and conferring a high biosafety level.
The new nanoparticles have demonstrated an ability to efficiently enter human primary dendritic cells, and have been tested for their ability to induce an immune response through different ways of administration in an Ovalbumin mouse model. Furthermore, they can induce high protection with a mouse malaria model.
GreyRigge Associates
A biotech consultancy that works internationally helping both small and large biopharmaceutical companies in the development of their medicines. Offers both technical and commercial support for biotech products across a wide range of large molecule product types including vaccines, gene and cell therapies, monoclonal antibodies, recombinant proteins, and peptides.
GRA offers both consultancy and training services to clients covering all CMC elements that include process and analytical development, formulation design and filling of biologics, quality assurance as well as non-clinical activities, including complex statistical analysis and support on CMC, non-clinical, and clinical.
Has experience in product characterisation and product stability evaluation, including specifications, supporting CMC elements together with their regulatory strategy and submissions.
Experienced in process characterisation and validation and the generation of process control strategies. GRA has expertise that includes scale down models and manufacturing developers. GRA are QbD practitioners, including advising on risk assessments and the appropriate use of statistics for experiment design to determine process operating ranges.
HiLung
At HiLung the team uses proprietary respiratory cell differentiation and engineering technologies to mass produce airway and alveolar epithelial cells and organoids from human iPSCs (induced pluripotent stem cells) in both 2D and 3D formats, with added complexity as needed, such as macrophages and fibroblasts.
The very human-relevant cells can be used for various purposes, from assessment of epithelial entry/uptake and antibody activity in vitro, to generation of viral and respiratory subcellular compounds as vaccine components, using respiratory cells as organic production beds.
More readily, they offer CRO services assessing therapeutic candidates, for disease such as respiratory infections, pulmonary fibrosis and cystic fibrosis, and for lung toxicity and pollutant particle screening. The organoids’ accessibility and additive complexity enable unique and highly reproducible opportunities for granular analysis such as single cell-seq and cytokine profiling.
They also offer underlying alveolar and airway cell plates for customers as ready-to-use, room temperature shipment in both ALI and conventional submerged formats. The latter has high throughput as 96- and 384-well plates, which are particularly useful in respiratory pandemic preparedness contexts.
Offers novel and human-relevant insights from the unique platform technology by “Translating human(e) inspiration”.
We also offer underlying alveolar and airway cell plates for customers as ready-to-use, room temperature shipment, in both in ALI (air-liquid interface) and in conventional submerged formats, the latter with high throughput as 96- and 384-well plates – which are particularly useful in respiratory pandemic preparedness context. We offer novel and human-relevant insights from our unique platform technology, by “Translating human(e) inspiration”.
If you would like to join your colleagues in this exciting and continuously growing start-up zone, fill out an application here or contact Isabella here: isabella.aung@terrapinn.com
Stay tuned for more start-up news, and make sure you subscribe to our weekly newsletters!
The University of Cambridge announced in September 2023 that a vaccine antigen technology developed in collaboration with spin-out DIOSynVax in early 2020 demonstrated protection against all known variants of SARS-CoV-2 and other major coronaviruses. With a paper published in Nature Biomedical Engineering, the team show that the vaccine candidate provoked a strong immune response against a range of coronaviruses.
DIOSynVax technology
The paper describes how, to meet the need for increased coverage to all the viruses of the sarbecovirus subgenus of betacoronaviruses, the researchers used a digitally immune-optimised synthetic vaccine (DIOSynVax) technology to design antigens. The antigens, computationally immune-optimised and structurally engineered, are selected in vivo to induce immune responses across a group of related viruses.
DIOSynVax combines computational biology, protein structure, immune optimisation, and synthetic biology to “maximise and widen the spectrum of protection” provided by vaccines. The researchers target the “Achilles heel” of the virus through this approach; identifying critical regions through computer simulations and selecting conserved structurally engineered antigens.
Professor Jonathan Heeney of the Department of Veterinary Medicine at University of Cambridge believes that this approach creates a vaccine “with a broad effect that viruses will have trouble getting around”. The chosen, optimised antigen is reportedly compatible with all vaccine delivery systems: it has been administered as a DNA immunogen, a weakened virus, and an mRNA vaccine. Every time the antigen generated a strong immune response. Following animal trials, the first-in-human trials are taking place.
Opening vaccine doors
Professor Heeney contrasts this technology with “current vaccines that use wild-type viruses or parts or viruses that have caused trouble in the past”.
“This technology combines lessons learned from nature’s mistakes and aims to protect us from the future.”
The synthetic antigens “generate broad immune responses, targeted to the key sites of the virus”.
“It opens the door for vaccines against viruses that we don’t yet know about. This is an exceptionally different vaccine technology – it’s a real turning point.”
Professor Heeney is set to join us at the Congress in Barcelona next month. Have you bought your tickets yet? Don’t forget to subscribe for more insights and updates.
In September the UKHSA announced an agreed deal for “millions of life-saving vaccines” has been signed with CSL Seqirus. The advance purchase agreement (APA) ensures that CSL Seqirus is “on standby” to produce over 100 million influenza vaccines if an influenza pandemic is declared. The vaccines would be produced at an existing manufacturing plant in Liverpool.
Another pandemic?
UKHSA states that pandemic influenza differs from seasonal influenza and avian influenza. If a new strain become global, transmitting from person to person, WHO could categorise it as the cause of a pandemic. Historically, these events are “highly unpredictable”, from timing to severity. In the past 100 years there have been 4 influenza pandemics: 1918, 1957, 1968, and 2009. The first of these caused over 50 million deaths worldwide. Pandemic influenza remains a “major health security concern”.
The UK prepares
UKHSA states that similar agreements have been arranged in the past, but this is the first time that the manufacturing process will be based in the UK, which gives “better security of access” should global demand outweigh supply. The vaccines will target the specific flu strain identified and declared to be a pandemic by WHO.
Professor Dame Jenny Harries, Chief Executive of UKHSA, is learning from “past pandemic events”, such as COVID-19, that “access to effective vaccines is vital” to save lives and minimise disruptions.
“This agreement represents a major step forward in our preparedness against future influenza pandemics.”
She also believes that basing the manufacturing of these vaccines in the UK “gives us speedier and more secure access”, which will facilitate a faster rollout. Maria Caulfield, Vaccines Minister, commented that the deal puts the UK “on the front foot” if an influenza pandemic should arise.
“It will ensure vaccines are manufactured in the UK – enabling us to get jabs into arms fast regardless of global demand and save thousands of lives.”
Marc Lacey, Global Executive Director at CSL Seqirus, described his organisation as a “global leader in pandemic influenza preparedness”. He’s “pleased” by this partnership.
“This agreement will help to ensure the UK maintains robust preparedness and rapid response capabilities for this potential future threat.”
How prepared is your country for a potential influenza pandemic? Will this partnership be sufficient and, should a pandemic rear its head, will it be enacted adequately? For more pandemic insights don’t forget to subscribe to our weekly newsletters.
In September 2023 the Pandemic Centre at Brown University School of Public Health shared a publication that emphasises the importance of “identification, attribution, and consequence management” of pathogen releases in Africa. The report offers a “roadmap” for the preparation for accidental or deliberate release, comprising “expert input” from “those on the frontlines”. In this piece we explore the guidance that is offered, which is intended for application “to a range of settings” apart from the specific geography that is used. To read the report in full click here, and don’t forget to let us know what you think!
A roadmap for preparation
The report begins with a foreword from Director, DrPH Jennifer Nuzzo, who comments on the “direct evidence” from COVID-19 that societies are vulnerable to biological threats.
“As governments move on from the pandemic emergency, we should not forget how much we’ve lost during this crisis – a consequence of our lack of preparedness for biological threats.”
DrPH Nuzzo emphasises that our preparedness for “future biological emergencies” depends on recognition of “other plausible disease scenarios” that could threaten “health, peace, and prosperity”. These scenarios include the two of the “most challenging”: accidental or deliberate release of a deadly biological agent. She suggests that the report will offer a “roadmap”; although it is addressed to a “particular geography in mind (Africa)”, the authors make it clear that the recommendations have relevance elsewhere.
“We may hope that future biological crises don’t occur, but hope is not a strategy for being prepared.”
The executive summary acknowledges that African countries are “by no means alone in lacking the tools” to respond to incidents caused by accidental or deliberate pathogen release. However, the policy brief is focused on Africa.
The importance of origins
Three types of outbreaks are presented as threats to public health:
Naturally occurring – those resulting from the transmission and spread of infectious diseases in the absence of human intervention of through human contact with wildlife
Those caused by accidental pathogen release – caused by laboratory mishap, unintended pathogen releases linked to lawful or illicit activities, or human error in handling dangerous materials
Those caused by deliberate pathogen release – intentional release or dissemination of pathogens to cause harm, instil fear, or disrupt societies
The authors suggest that “recent growth in laboratory systems” and “widespread access to innovative but potentially dangerous technologies” create a “new species of trouble. This requires a “re-evaluation of the threat landscape”. African countries have protocols addressing naturally occurring outbreaks, but “fewer policy measures” to govern accidental or deliberate outbreaks.
There are several reasons for the importance of determining the origin or an outbreak as identified in the report:
Identify the source – this is crucial for implementing effective control measures to prevent the further spread of the disease
Understand the epidemiology of the disease – this informs public health policies and interventions
Identify potential risk factors for the disease – this can inform prevention strategies
Alleviate public anxiety and fear (as demonstrated by the COVID-19 pandemic)
Where accidental, identify which threat and risk reduction measures to take to build resilience in biosecurity and biodefence systems
Where deliberate, and if possible, preserve the integrity of the crime scene and collect evidence to prevent further attacks, identify victims, and pursue and prosecute offenders
The report serves as a “multi-sectoral complement” to Africa CDC’s Biosafety and Biosecurity Initiative’s Model Legal Framework. The Initiative was launched in April 2019 to improve outbreak assessment, facilitating appropriate responses. This was pushed forward with the development of a strategic plan (2021-2025), which outlined a coordinated approach to strengthen biosafety and biosecurity. Priority area 6 in the plan seeks to enhance infrastructure, training, and capacity building for the prevention, detection, and response to biological events. The report authors suggest that policies are needed to identify and manage pathogen releases.
Protocols for naturally occurring pathogens
According to the report, African countries do have a “range of protocols, strategies, policies, and systems” to address naturally occurring pathogens. These range from a framework for early detection to epidemic-prone diseases, to the creation of Africa CDC, or the establishment of a One Health programme and coordination group. From the stated protocols and policies, the authors infer:
Natural outbreaks are those resulting from the transmission and spread of infectious disease in the absence of accidental or deliberate release.
They can occur because of zoonotic infections, environmental changes, contamination food, water, and environment, or the emergence of new pathogens or re-emergence of agents.
Understanding the characteristics and patterns of natural outbreaks is crucial for effective response and consequence management.
Implementing several measures is vital to effectively manage a crisis or outbreak’s economic, social, and political consequences.
Protocols for accidental release of pathogens
Accidental outbreaks have “profound implications” for both public health and law enforcement. Thus, a “systematic approach” is needed. The authors state that there are several “essential factors” to consider. These include “characterising and documenting laboratory accidents and unintended releases and possessing the necessary expertise and technologies for identification and confirmation”.
Effective threat-reduction measures can mitigate the accidental release of pathogens, including:
Robust biosafety and biosecurity protocols
Identification of country specific high priority pathogens and conducting risk assessments to check preparedness, response, and mitigation methods
Adequate training and education
Simulation exercises
Robust facility design
Regular inspections and audits
Incident reporting and investigation
Risk assessment and management
International standards and collaboration
Research into effective biosafety and biosecurity measures
Implementing these measures can “significantly reduce” the risk of accidental releases.
Protocols for deliberate release of pathogens
Deliberate outbreaks can be caused to “cause harm, instil fear, or disrupt societies”. These can result from:
Biocrime – threatening to release or using a disease-causing biological agent or toxin to harm or kill an individual or a small group motivated by revenge or the pursuit of monetary gain through extortion or other means.
Bioterrorism – threats or intentional releases of viruses, bacteria, or other agents or toxins to cause illness or death in people, animals, or plants, driven by ideological, religious, or political beliefs and seeks to create casualties, instil fear, disrupt society, or cause economic losses.
Biowarfare – using disease-causing agents as weapons, prohibited under the Biological and Toxin Weapon Convention.
“The timely detection and confirmation of deliberate outbreaks requires specialised expertise and advanced technologies within public health and law enforcement.”
The pursuit of next-generation sequencing technologies allows “unprecedented resolution” and “improved understanding” of pathogen transmission dynamics. Other techniques have also been used, and web-based surveillance tools, modelling, and epidemic intelligence methods are “crucial components” for outbreak detection and assessment.
The examples of “consequence management” measures include:
Public health emergency response
Medical treatment and isolation
Contract tracing and quarantine
Mass vaccination or prophylaxis
Risk communication and public awareness
Decontamination and environmental remediation
Psychological and social support
Investigation and law enforcement
The measures are “coordinated and multidisciplinary”, with the goal of minimising the effects of deliberate pathogen release outbreaks, protecting public health, and restoring “normal functioning within affected communities”.
WOAH’s algorithm
WOAH proposes an algorithm for handling a suspicious biological event, which can be divided into three main areas of importance:
Plan
Assess and respond
Recover
One Health and multidisciplinary approaches
“Using a One Health strategy, countries should foster collaboration and information sharing among national and regional public health agencies, research institutions, academia, veterinary, agricultural, and environmental services, and international partners.”
This will demand the facilitation of joint investigations and data sharing as well as the establishment of communication channels and platforms for immediate exchange of “information, best practices, and lessons learned”.
Going forward
The brief outlines the importance of an outbreak assessment and consequence management framework to African public health. Such a framework would allow the continent to quickly detect and assess outbreaks, accurately determining their origins, and implementing consequence management pathways in response.
“The increasing threat of accidental and deliberate release of biological agents constitutes a new species of trouble in global health. Governments, public health agencies, and relevant stakeholders must prioritise establishing this framework, allocating necessary resources, and collaborating effectively to ensure its successful implementation.”
What key lessons did you identify in the brief, and how are they relevant to your region if you are not based in Africa? For more discussions on the importance and intricacies of outbreak prevention and management, don’t forget to get your tickets to the Congress in Barcelona next month, and subscribe to our weekly newsletter here.
At the United Nations General Assembly high-level meeting on tuberculosis world leaders approved a political declaration “reaffirming their collective commitment” to end the infectious disease by 2030. In a move recognised by WHO, Member States committed to “urgently strengthen measures” to reduce deaths, continue support for the WHO Multisectoral Accountability Framework for tuberculosis, and implement national plans or strategies with “multisectoral approaches”. At the summit, calls for a new, improved vaccine were also heard.
They put a man on the moon
Dennis Francis, President of the General Assembly, opened the meeting with a comment on the lack of success against the disease:
“Why, after all the progress we have made – from sending a man to the moon to bringing the world to our fingertips – have we been unable to defeat a preventable but curable disease that kills over 4,400 people a day?”
Breaking into a chant of “end TB”, he called upon stakeholders to accelerate innovation towards a suitable vaccine. The importance of vaccine development was emphasised by Dr Tedros Adhanom Ghebreyesus, WHO Director-General, who recalled that the only licensed vaccine was developed over a century ago.
“We have an opportunity that no generation in the history of humanity has had: the opportunity to write the final chapter in the story of TB.”
Infectious environments
Amina J. Mohammed, Deputy Secretary-General, suggested that armed conflict, economic upheavals, and climate disasters facilitate the spread of infectious diseases by creating a “breeding ground” and following a vicious cycle that perpetuates inequality. She urged Member States to prioritise the disease in their national agendas, reflecting on the sad death of her own father to tuberculosis.
“What we need is a vaccine. Let’s end tuberculosis now. It’s possible.”
Political commitment
Paula Narváez, President of the Economic and Social Council, demanded “strong political commitment to the very highest levels”. She observed that the high-level meetings on health during the week demonstrated the links between universal health, pandemic preparedness, and ending tuberculosis. She highlighted the Council’s important role in these challenges.
A powerful perspective was presented by tuberculosis survivor and author of Stigmatised: A Mongolian Girl’s Journey from Stigma & Illness to Empowerment, Handaa Enkh-Amgalan. She repeated the words of her doctor when she was diagnosed with the disease 12 years ago: “do not tell anyone”. She stated that “stigma costs lives”, drawing attention to the role of social expectations, particularly of women and girls, in delaying detection and treatment. She called on world leaders to prioritise the provision of support to affected populations to reduce this stigma.
WHO weighs in
In a release from WHO the magnitude of our current position was highlighted by the Director General.
“For millennia, our ancestors have suffered and died with tuberculosis, without knowing what it was, what caused it, or how to stop it. Today, we have knowledge and tools they could only have dreamed of. The political declaration countries approved today, and the new targets they have set, are a commitment to use those tools, and develop new ones, to write the final chapter in the story of TB.”
So, what are the targets set and tools available? WHO states that, although global efforts have saved “over 75 million lives”, we have fallen short of targets already. This is largely due to the disruptions caused by the COVID-19 pandemic. The new targets include reaching 90% of people with TB prevention and care services, using a WHO-recommended rapid test as a first diagnostic method, providing social benefit packages to all people with TB, licensing at least one new vaccine, and closing funding gaps by 2027.
Dr Tereza Kaseva, Director of the WHO Global TB Programme, hopes the opportunity to unite on the response will “accelerate action and strengthen health systems” for TB and “broader health and well-being” concerns.
“Averting TB-related financial hardship and preventing the development of the disease in vulnerable groups will help diminish inequities within and between countries.”
Vaccine Accelerator Council
In January 2023, Dr Tedros Adhanom Ghebreyesus announced plans to establish a “TB Vaccine Accelerator Council” to facilitate the “development, testing, authorisation, and use” of new TB vaccines. The Council convened for an establishment meeting on 20th September 2023. The Council is supported by the WHO secretariat, with subsidiary bodies to support its engagement and interaction with sectors and stakeholders.
Do you think the latest updates from global leaders are enough to bring about adequate action, and will we succeed in meeting tuberculosis goals? For more on health targets don’t forget to subscribe to our newsletters here.
Data from the WHO published in September 2023 offer an insight into the extent of cholera surges across the world. The comprehensive statistics for 2022 reveal that cases reported to WHO were “more than double” than those reported in 2021. The frequency and severity of outbreaks have increased, yet data remain “inadequate”.
A 7th pandemic
The report introduces 2022 as the year of a “7th cholera pandemic”, comparing the cases reported to WHO with those reported during the previous year. An area for concern is the change in geographical pattern of outbreaks, with countries that had not reported cholera in “many years” reporting outbreaks in 2022. Notable details include:
472,697 cases were reported, compared with 223,370 in 2021
44 countries reported cases, an increase from 35 in 2021
7 countries reported outbreaks comprising over 10,000 suspected and confirmed cases
What is driving this increase?
WHO suggests that conflict, climate change, and “limited investment in development and population displacement due to emerging and re-emerging vulnerability” contributed to increased outbreaks. Furthermore, the end of COVID-19 restrictions, including a reduction in prevention and control measures and reduced outbreak response funding come into play.
Cholera spreads through good and water contaminated with faecal matter that contains the Vibrio cholerae bacterium. Transmission is associated with a lack of adequate sanitation, often linked to “underdevelopment, poverty, and conflict”. The increased demand for cholera countermeasures has been “a challenge”, says WHO. In October 2022, the International Coordinating Group (ICG) suspended the standard two-dose vaccination regimen in outbreak response campaign, moving to a single-dose approach.
The surge continues
Unfortunately, data for 2023 so far suggest that the global increase is continuing; 24 countries are reporting active outbreaks, with some in the midst of “acute crises”. WHO continues to offer support to countries with activities in public health surveillance, health management, and prevention measures.
The UK’s International Development Minister Andrew Mitchell and Health Minister Will Quince announced investments in “ground-breaking research and development” at the United Nations General Assembly (UNGA) 78th session in September 2023. The government describes these investments as an effort to “tackle the world’s most pressing health challenges”. UK scientific expertise is to be “harnessed to boost health security around the world”.
Research and development
The investment includes up to £103.5 million to develop affordable vaccines through the UK Vaccine Network, which unites industry, academia, and funding bodies in an advisory capacity for the Department of Health and Social Care. The funding will cover other health products and treatments that will “halt the spread of infectious diseases” and support programmes to protect sexual and reproductive health.
The UK will also contribute to research and development into “cutting-edge technology” that enables quick responses to disease outbreaks and improves the health of vulnerable populations in low- and middle-income countries. £295 million will go towards the development of new methods of drug administration to ensure that life-saving care reaches remote areas.
“This new package of R&D will bolster the world’s ability to respond swiftly and effectively to disease outbreaks.”
Included are a previously announced pledge from the Foreign, Commonwealth, and Development Office to CEPI and £5 million of additional funding for the TB Alliance. An additional £95 million will go to the Tackling Deadly Diseases in Africa Programme II; this partners with Kenya, Ghana, Uganda, Malawi, Democratic Republic of Congo, WHO, and Africa CDC to “detect and tackle future epidemics, drug resistant infections, and climate change.
Back on track for SDGs
Andrew Mitchell commented that the UK is “committed to reinvigorating progress” towards the Sustainable Development Goals (SDGs).
“The UK’s significant support for global health announced at the UN General Assembly this week will be truly transformational in creating more resilient and inclusive health systems worldwide.”
Will Quince agreed that the investment is “vital for saving lives – both at home and abroad”.
“This UK Vaccine Network investment will help deliver effective and accessible vaccines for populations threatened by infectious diseases and cements the UK’s status as a leader in global health research.”
Do you think this is an adequate financial contribution to global health goals from the UK, or could more done to secure a return to progress towards SDGs? For more updates like this, don’t forget to subscribe.
In September 2023 Vir Biotechnology announced that the first participant in a Phase I trial has been dosed. The trial of VIR-1388 will evaluate the safety, reactogenicity, and immunogenicity of the investigational novel T cell vaccine for the prevention of human immunodeficiency virus (HIV). Initial data from the trial are expected in the latter half of 2024.
VIR-1388
VIR-1388 is an investigational subcutaneously administered HIV T cell vaccine based on the human cytomegalovirus (HCMV) vector platform. It is designed to elicit “abundant” T cells that recognise several HIV proteins in a different way to that of previous vaccine efforts. VIR-1388 applies lessons from VIR-1111, an investigational proof-of-concept vaccine, with the goal of creating a safe and effective HIV vaccine.
The vector is a weakened version of the virus, designed to deliver the vaccine material to the immune system “without causing disease” in participants. HCMV has been present in “much of the global population for centuries”, with most people experiencing no symptoms and being unaware of infection. It remains detectable in the body for life. Thus, the team at Vir believe it could deliver and help the body retain vaccine material for a long period.
The trial
The Phase I trial is randomised, double-blind, and placebo-controlled evaluation of the safety, reactogenicity, and immunogenicity of three different doses of VIR-1388 compared with placebo. It is expected to enrol around 95 participants between the ages of 18 and 55 who are not living with HIV, with existing antibodies specific to HCMV, and in overall good health.
The study comprises two parts; Part A is a lead-in phase enrolling a limited number of HCMV-positive patients of non-childbearing potential with a frequent safety monitoring schedule. The second part, Part B, expands enrolment to a broader population of HCMV-positive patients, including persons of childbearing potential. An optional long-term follow-up study will increase participation for up to three years after the first dose.
The trial is supported by NIAID and the Bill & Melinda Gates Foundation. It takes place across international sites within the federally funded HIV Vaccine Trials Network (HVTN).
A major challenge and a clinical milestone
UNAIDS estimates that in 2021 around 1.5 million people were newly infected with HIV, with around 650,000 dying from AIDS-related deaths. Dr Carey Hwang, Vir’s Senior Vice President, Clinical Research, Head of Chronic Infection, describes HIV as a continued “major global public health challenge” that persists despite “decades of research efforts”.
“The initiation of our first clinical trial evaluating VIR-1388 is an important clinical milestone in our pursuit of developing an HIV vaccine.”
Dr Hwang hopes that the “unique approach” will “help close the longstanding public health gap in HIV prevention”.
In September 2023 Google’s AI organisation, DeepMind, released a catalogue of genetic mutations intended to accelerate disease diagnosis and enable improvements to medical interventions. DeepMind, a team of “scientists, engineers, ethicists, and more” is “committed to solving intelligence” for the advancement of science and benefit of humanity. The new release is a catalogue of missense mutations that provides an insight into the effect of genetic mutations that affect the function of human proteins.
AlphaMissense
AlphaMissense is DeepMind’s AI model for the classification of missense variants. A recent publication reveals that it categorised 89% of 71 million possible missense variants as likely pathogenic or likely benign. The paper presents AlphaMissense as a combination of existing strategies:
Training on weak labels from population frequency data, avoiding circularity by not using human annotations
Incorporating an unsupervised protein language modelling task to learn amino acid distributions conditioned on sequence context
Incorporating structural context by using an AlphaFold-derived system
AlphaMissense uses input from an amino acid sequence to predict the pathogenicity of “all possible single amino acid changes” at a given position in the sequence.
“Notably, AlphaMissense does not predict the structural changes of the mutated amino acid sequences but instead predicts pathogenicity as scalar values.”
Missense mutations
A missense mutation, or variant, is a DNA change that causes different amino acids to be encoded at a particular position in the resulting protein. Some mutations can alter the function of the resulting protein. DeepMind compares DNA to language, commenting that changing one letter can “change a word and alter the meaning of a sentence”. Just so, a substitution in DNA changes which amino acid is “translated”.
Each person carries over 9,000 missense variants, of which most are benign. However, some are pathogenic and can “severely disrupt protein function”. They can be used in the diagnosis of rare genetic diseases and are also important for studying “complex diseases”, which are caused by a “combination” of changes.
Classifying missense variants is an “important step” in understanding the pathway to disease. Of over 4 million missense variants that have been identified in humans, only 2% have been annotated as pathogenic or benign. This comprises around 0.1% of all 71 million possible variants.
What does this mean for health?
DeepMind states that a “key step” in using this research is “collaborating with the scientific community”. In partnership with Genomics England, the team is exploring how the predictions could help study the genetics of rare diseases. Although the predictions are not intended for clinical use and should be “interpreted with other sources of evidence”, the work has potential to improve disease diagnosis and discovery.
“Ultimately, we hope that AlphaMissense, together with other tools, will allow researchers to better understand diseases and develop new life-saving treatments.”
Taking steps forward
BBC Newsreported that a “leading independent scientist” identifies this work as a “big step forward”. Professor Ewan Birney, deputy director general of the European Molecular Biology Laboratory, believes it will allow researchers to “prioritise where to look” for areas that cause disease. He thinks AI is going to play a greater role in life sciences with time:
“I don’t know where it’s going to end but it’s changing nearly everything we do at the moment.”
Dr Ellen Thomas, deputy chief medical officer at Genomics England, is excited by the “new tool”.
“It will help clinical scientists make sense of genetic data.”
Will these changes affect your work? How might vaccine development benefit from AI support? For more like this don’t forget to subscribe to our weekly newsletters.
At the United Nations General Assembly (UNGA) 78th session in September 2023 a “landmark declaration” was adopted on pandemic prevention, preparedness, and response. This was the General Assembly’s first ever high-level meeting on the subject, which WHO welcomed. Describing the “historic commitment”, WHO recognised the need for “international cooperation, coordination, governance, and investment” to prevent a repeat of the COVID-19 experience. This declaration will also support efforts to “get back on track” with the Sustainable Development Goals (SDGs).
“Making the world safer”
The Assembly convened under the theme “Making the world safer: Creating and maintaining political momentum and solidarity for Pandemic Prevention, Preparedness, and Response”. The meeting began with comments from Assembly President Dennis Francis, who reflected on the COVID-19 pandemic as “one of the most pressing global challenges of our time”.
“The reality is that we simply lacked preparation and responsiveness.”
Further to the collective lack of preparation, Mr Francis noted the global inequalities that were highlighted. This concern was echoed by Member States in the Political Declaration, where “glaring inequalities” in access to vaccines were recorded.
Political Declaration
The Political Declaration outlines a range of recommendations including:
Conclude negotiations on a WHO convention, agreement, or other international instrument on pandemic prevention, preparedness, and response (aka the Pandemic Accord).
In line with the Pandemic Accord process, ensure the sustainable, affordable, fair, equitable, effective, efficient, and timely access to medical countermeasures.
Take measures to counter and address the health-related misinformation, disinformation, hate speech, and stigmatisation.
Invest in primary health care and other health system measures.
Under-Secretary-General’s concerns
UN Under-Secretary-General Amina J. Mohammed emphasised the need to follow these recommendations to prevent a repeat of vaccine hoarding by richer countries. The document also called for the promotion of equitable distribution of affordable and quality medicines, and the reaffirmation of the World Trade Organisation (WTO) Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS). This agreement “plays a critical role” in encouraging trade in “knowledge and creativity”, resolving intellectual property trade disputes, and “assuring WTO members the latitude to achieve their domestic objectives”.
Ms Mohammed also demanded reform of the international financial architecture to reduce the debt burden of developing countries. She requested long-term financing of more than $500 billion each year within the SDGs recovery plan. Another area of attention for Ms Mohammed was the need to fight misinformation about vaccines. She gave the example of a code of conduct on digital platforms and proposed the creation of an emergency coordination platform to respond to complex international shocks.
WHO Director-General’s view
Dr Tedros Adhanom Ghebreyesus commented that the adoption of this Political Declaration is “a historic milestone”. He urged the Member States to implement the commitments outlined in the document. Furthermore, he called for an agreement by May 2024 for the drafting of the WHO international instrument on prevention, preparedness, and response.
“The lived experience of people who suffered through the COVID-19 pandemic must be at the forefront of our minds going forward in order to realise the clear direction provided by world leaders. We must learn how to protect our communities better and to engage, inform, and empower them to be part of the solution.”
He remarked upon the need for “concrete actions” to promote equitable access to medical countermeasures, appropriate financing, “empowered and engaged communities”, and “robust, trained, and equipped health workers”.
“The world needs a more collaborative, cohesive, and equitable approach to preventing, preparing for, and responding to pandemics.”
Spend to save
World Bank Senior Managing Director Axel Van Trotsenburg welcomed the first annniversary of the pandemic fund, which secured pledges from 133 countries of $2 billion. This is a “very good starting point”, but Mr Trotsenburg called for $10 billion. The High-Level Champion for Pandemic Prevention, Preparedness, and Response, Helen Clark, called for a global financing system capable of immediately responding to pandemics.
“Spending billions will save trillions.”
She suggested that vaccines, diagnostics, and treatments should be considered “global common goods”.
“Viruses that can cause pandemics will not wait for diplomacy to produce results.”
During the meeting it was proposed that a dedicated global coordination body should be created. Ms Clarck emphasised that the “political choice” of Member States will determine if COVID-19 is the “last pandemic to cause such devastation”.
In September 2023 CEPI and Bio Farmer announced the agreement of a 10-year partnership to “boost rapid manufacturing of outbreak vaccines” at Indonesia’s “leading” vaccine manufacturer. This partnership is intended to bring mRNA and viral vector rapid response vaccine manufacturing technologies to Indonesia and the ASEAN region. Furthermore, manufacturing capacity will be reserved to supply Global South countries during future outbreaks and pandemics as a lesson from the COVID-19 pandemic.
The importance of global manufacturing
CEPI refers to a study in Nature from 2022 that suggests that if COVID-19 vaccines had been better shared, 295.8 million infections and 1.3 million deaths might have been averted.
“One of the central reasons behind the tragic vaccine inequity which characterised the response to COVID-19 was the concentration of global vaccine manufacturing capacity in a small number of high income and/or high population countries.”
This concentration left “much of the Global South” without timely access to the life-saving vaccines developed in response to the pandemic. CEPI’s goal of enabling equitable access highlights the importance of “expanding and diversifying the global footprint” of vaccine manufacturing. With a network of vaccine manufacturers in Global South countries, particularly in areas at high risk of disease outbreaks, CEPI hopes to strengthen our preparedness and responses to health threats.
Welcoming Bio Farma
Bio Farma joins a CEPI-backed network of vaccine manufacturers aiming to substantially increase the world’s capacity and capability to produce vaccines against disease threats in as little as 100 days (the 100 Days Mission). Bio Farma has a “broad portfolio” of vaccines, including some WHO prequalified vaccines.
CEPI will provide funding of up to $15 million to diversify Bio Farma’s manufacturing capability and support the establishment of mRNA and viral vector rapid response technologies at Bio Farma’s facilities. This will accelerate the team’s ability to manufacture vaccines against viral threats. The funding complements funding from the Indonesian Government and Bio Farma’s participation in the mRNA technology transfer programme.
Expanding capacity
The partnership will allow Bio Farma to establish a bioprocess laboratory to develop and test new mRNA and viral vector technologies. It will also support Good Manufacturing Practice (GMP)-standard facilities to produce batches of vaccines for clinical trials up to Phase II and GMP-standard capacity for the manufacture of larger quantities of vaccine for use in Phase III trials and commercial supply.
Once established, these facilities will supply mRNA and viral vector vaccines against a range of future outbreak threats within 100 days. Notably, the partnership reserves a proportion of overall manufacturing capacity for supply to countries in the Global South in the case of an outbreak, as directed by CEPI.
Dr Richard Hatchett, CEPI’s CEO, commented that the world “needs to be able to respond rapidly, and equitably” to future threats “before they mushroom into pandemics”.
“Our collaboration with Bio Farma will contribute to this goal by expanding the company’s world-class manufacturing facilities to include the very latest mRNA and viral vector technologies which will be capable of producing outbreak vaccines in as little as 100 days.”
Dr Hatchett emphasised that the mRNA manufacturing capacity will help to “enable swift and equitable access to outbreak vaccines for countries in the ASEAN region”. Shadiq Akasya, President Director of Bio Farma, looks forward to collaboration with CEPI, which will “undoubtedly enable manufacturers” to “acquire capability in producing outbreak vaccines”.
“This momentous collaboration is justification of Bio Farma’s commitment to global health and Indonesia’s contribution in achieving vaccine equity during outbreaks particularly in the ASEAN region.”
Bio Farma is “eager” to “explore mutually beneficial opportunities” to improve the quality of life. The Republic of Indonesia’s Minister of Health, Budi G. Sadikin, is pleased to “recognise the significance of this collaboration”.
“By partnering with CEPI, Indonesia will enhance its contribution to vaccine security and self-reliance, particularly within ASEAN and the Global South.”
Lucia Rizka Andalucia, Director of Pharmaceuticals and Medical Devices at the Ministry of Health for the Republic of Indonesia, is hopeful that Bio Farma will be able to “strengthen its research and manufacturing capabilities”.
“Bio Farma has long been a key player in combatting communicable diseases by supplying vaccines for both domestic and global needs.”
With less than a month until the World Vaccine Congress in Barcelona, our start-up zone is continuing to grow! This week we are pleased to present another set of organisations that have already secured their spaces in the zone. To see previous introductions head over to our technology section.
Why be a start-up at the World Vaccine Congress?
Start-ups whose applications are successful are entitled to several unique benefits, including exhibition wall space, 2 complimentary passes, and marketing materials. For the first time at this event, there is the opportunity to participate in a 5-minute pitch during lunch breaks, an exciting way of introducing yourselves to colleagues and potential partners.
Our wonderful start-up manager, Isabella Aung, will receive your application and guide you through the process. She is looking forward to hearing more from interested companies, so do get in touch with her here via email (isabella.aung@terrapinn.com) or head straight to the application page here.
“I am super excited to connect with and welcome even more start-ups to our start-up zone at our Congress this October! It’s going to be our biggest and most exciting start-up zone yet!”
Introducing…
Belyntic
Resident viruses like EBV or CMV threaten millions of immunocompromised people and are associated with the development of the most threatening diseases of our time, such as cancer or Alzheimer’s.
Belyntic wants to leverage the power of the human immune system, particularly the T-cell repertoire, to eradicate such unmet viral diseases.
The team uses a platform technology based on self-adjuvant peptides, and hopes to enable the development of prophylactic and therapeutic nanovaccines.
NEOMatrix
A biotech founded in 2020 by scientists who were leading cancer vaccine programmes in MSD and Takis Biotech. The team is recognised for the conception and implementation of many innovative technologies to improve in vivo gene transfer, regulation of gene expression, and immunogenicity.
NEOMatrix’s objective is the production of patient-specific DNA-based Neoantigen Cancer Vaccines (NCV) built on sequencing the genetic map of the tumour and identification of neoantigens, specific mutations that are present only on cancer cells.
The approach was demonstrated to be efficient at preventing tumour growth and strongly improving immune responses against cancer in combination with immune checkpoint inhibitors.
The targeted procedure for production and delivery of NEOMatrix is based on a fast process that includes:
sampling specific tumour DNA
sequencing this DNA
identification of mutation
synthesis of the right DNA sequence for the specific tumour
delivery through DNA Electroporation (EP)
NEOMatrix is based on synthetic DNA, the ideal platform for bringing individualised neoantigen vaccines to the market, being usable in multiple deliveries for treating different metastases in the same patient, and being easier to produce and handle at reasonable costs with high numbers of neoepitopes.
Oxford SimCell
A biotechnology spinout from the University of Oxford and the exclusive licensee of SimCell technology.
SimCell technology puts a new spin on a very traditional kind of vaccine – inactivated whole bacterial cells – which are used to protect against bacterial pathogens.
The vaccines can be used as alternative countermeasures against critical bacteria that don’t respond to antibiotic drugs, such as Staphylococcus aureus and Pseudomonas aeruginosa.
The goal is to improve individual patient outcomes and help to tackle the overarching global challenge of AMR.
SimCells are genome-free bacteria, produced by expression of a nuclease in host bacteria that cuts the bacterial genome. The process renders the bacteria unable to replicate whilst preserving important immunogenic cell surface features. The SimCells cannot grow but are otherwise identical to their live counterparts, and are ideal for use as inactivated whole-cell vaccines; SimCell vaccines exhibit a full complement of cell surface antigens in their native conformation and context, generating a comprehensive immune response.
Apex Research Group
A clinician-led clinical research site organisation committed to preserving the health and well-being of the general population by being a liaison between Pharma, Clinical Research Organisations (CROs), and prospective clinical trial participants.
Dedicated to researching diagnostics, medical devices, and therapeutics used in preventative care and treatment. With the singular goal of addressing unmet medical needs, ARG connects participants to clinical investigation and conducts studies on behalf of sponsors with promising investigational products in their pipelines. This includes vaccines, pharmaceutical medicines, and medical devices.
Connected to several Urgent Care clinics throughout Sacramento with a network that enables practical recruitment approaches to reach a wide range of potential study participants.
Committed to ensuring that all studies are conducted with the highest integrity to produce high quality data. With a focus on participant safety, the team employs a patient-centric approach to conducting clinical research and is guided by the ethical principles that support compassionate patient care.
bespark*bio
An innovative and independent process development organisation committed to developing sustainable manufacturing processes for viral vector-based medicines for clients.
Combines internal development with pharma service to stay at the forefront of science and technology with an innovation-driven portfolio.
Promotes a significant reduction of time to clinics, concurrently reducing risks of failure by generating sophisticated process understanding and simplifying customers’ journey from scientific breakthroughs to clinical development.
Operates in a cutting-edge process development facility, complemented by innovative digitalisation and data modelling approaches.
Builds on a highly experienced team of educated scientists, a renowned scientific advisory board, and a strong international network.
Champions service orientated and flexible collaborations based on mutual respect and reliability. The team understands partners’ needs.
If you would like to join your colleagues in this exciting and continuously growing start-up zone, fill out an application here or contact Isabella here: isabella.aung@terrapinn.com
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