by Charlotte Kilpatrick | Oct 24, 2024 | Technology |
The University of Connecticut (UConn) announced in October 2024 that associate Professor Thanh Nguyen’s research has received “significant” backing from The Bill and Melinda Gates Foundation. The Gates Foundation has awarded a series of grants totalling $6.6 million, following support from the National Institutes of Health (NIH) and the US Department of Agriculture (USDA). The funding will contribute to research and innovation for a microneedle array patch that can deliver multiple human vaccines at once. The Foundation initially awarded $2 million, which has increased after early success.
Microneedle array patch technology
Dr Thanh Nguyen works in the College of Engineering’s School of Mechanical, Aerospace, and Manufacturing Engineering. His microneedle method is “far less painful” than traditional syringe delivery and offers access and uptake benefits.
“What if we were able to mail people vaccines that don’t need refrigeration, and they could apply to their own skin like a bandage?”
The technology delivers highly concentrated vaccines in powder from over months, through a “nearly painless” 1-centimetre-square biodegradable patch.
“The primary argument is that getting vaccines and boosters is a pain. You have to go back two or three times to get these shots. With the microneedle platform, you put it on once, and it’s done.”
Funding increases
After the initial award of $2 million, the project made good progress and received additional funding to support the development of a scale-up manufacturing technology to produce patches on an industrial scale. In late September, the Gates Foundation awarded $4 million to take the patch “a step farther” as a pentavalent and Polio vaccine targeting diphtheria, tetanus, pertussis, HIV, Hepatitis B, and Polio. With this funding, the team can “build up productivity”. They are partnering with LTS to scale up production and are expanding the size of laboratory.
The award also marks a fundraising milestone for Dr Nguyen, who has earned more than $25 million in research awards, which he reflects “doesn’t come naturally”.
“It comes from the recognition of the high impact of the research and the lab’s success in publishing articles. It is a testament to the importance of what we are doing.”
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by Charlotte Kilpatrick | Oct 24, 2024 | Global Health |
In October 2024 the International Finance Facility for Immunisation (IFFIm) priced a US$1 billion, 3-year fixed-rate bond to fund “critical vaccine research and immunisation programmes”. This is IFFIm’s largest single benchmark transaction in the primary market since its inaugural benchmark in 2006, with proceeds supporting Gavi and CEPI. The bond will mature on 29th October 2027 and carries a semi-annual coupon of 4.125% and a semi-annual re-offer yield of 4.222%.
“The success of this bond highlights the ongoing strength of IFFIm’s model, which leverages sovereign support and strong financial structuring to offer investment opportunities that make a positive impact on children’s health.”
The order book was IFFIm’s largest to date, exceeding US$4 billion. The bond drew interest from a diverse group of investors with geographic spread.
Support for vaccine programmes
IFFIm is an “important flexible tool” for organisations like Gavi; since 2006 it has provided Gavi with US$5.8 billion in financing, one sixth of its overall budget. It has been “critical” in enabling Gavi’s recent emergency responses as well as routine immunisation and health system resilience efforts. Dr Sania Nishtar, CEO of Gavi, reflected that IFFIm has been a “groundbreaking and indispensable tool”.
“Today’s bond issue provides us with vital flexibility in our mission to protect millions of children from preventable diseases and to protect our world from the threat of future pandemics.”
As Gavi nears the end of the 2021-2025 strategic period and prepares for the next phase, IFFIm states that the bond issue will play a “pivotal role” in supporting life-saving programmes.
IFFIm has also provided approximately US$272 million in past financing to CEPI in support of the research and development of new vaccines. Dr Richard Hatchett, CEO of CEPI, acknowledged the “serious threat to global health security” presented by epidemics and pandemics. He commented that these can be “mitigated through investment in vaccine R&D and manufacturing”.
“The IFFIm financing mechanism enables CEPI to access the critical funding it needs to accelerate the development of vaccines against emerging infectious disease threats, for the benefit of all.”
Offering opportunities
IFFIm Board Chair Ken Lay believes that the latest issue “highlights IFFIm’s unparalleled strengths”; it is “backed by sovereign donors, driven by a vital global mission, and structured to maximise impact”.
“IFFIm’s bonds continue to offer investors compelling opportunities to earn competitive returns with good secondary market liquidity and assured use of proceeds.”
Jorge Familiar, Vice President and Treasurer, World Bank commented that capital markets are a “powerful tool for connecting private investment with global public goods”.
“As IFFIm’s Treasury Manager, the World Bank is pleased to support IFFIm in accessing capital markets to provide a long-term and flexible funding source to Gavi to accelerate access to vaccines and vaccine development.”
Head of SSA and EMEA IG Syndicate, BofA Securities Adrien de Naurois congratulated the IFFIm team on a successful return to the USD market.
“Today’s transaction, the first USD benchmark in two years, is a clear demonstration of IFFIm’s loyal and diverse investor base, attracted by the importance of its mission to deliver immunisation programmes to those most vulnerable via the ongoing work of Gavi.”
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by Charlotte Kilpatrick | Oct 17, 2024 | Global Health |
A study in The Lancet Global Health estimates the impact that the 100 Days Mission could have had on the COVID-19 pandemic. The authors find that the implementation of non-pharmaceutical interventions (NPIs) within the 100 Days Mission could have averted around 8.33 million deaths, corresponding to a monetary saving of US$14.35 trillion. Investment in manufacturing and health systems contribute an increase to 11.01 million deaths averted. The researchers comment on the value of the 100 Days Mission but emphasise the importance of “prioritising a more equitable global vaccine distribution”.
In search of greater vaccine benefits
Although COVID-19 vaccines are estimated to have prevented almost 20 million deaths, the authors demand a better understanding of the “further health and economic benefits that could have been achieved” through shorter development times and “improved global equity in pandemic preparedness”. CEPI’s 100 Days Mission was proposed in 2021, establishing the ambition of cutting vaccine development time for new pathogens to 100 days. This about a third of the time taken to deliver the first COVID-19 vaccine.
“The availability of COVID-19 vaccines within 100 days would have substantially changed the pandemic; however, these benefits would be finite without enabling equitable access to vaccine products through system equity.”
Various efforts to encourage global vaccine distribution were “hampered” by inequities, and it is recognised that manufacturing capacity should be “expanded but also diversified” to “promote self-sufficiency and regional resilience”. Furthermore, supply chains and infrastructure must be scaled to enable the delivery of vaccines that rely on cold-chain infrastructure.
The study
The searchers hoped to quantify the potential impact of the 100 Days Mission by retrospectively estimating the effect it would have had on the COVID-19 pandemic, thus offering evidence to support decision making around future investments in research and development capabilities. They also aimed to quantify the impact of “additional investments”.
The analyses use an extended version of a previously published compartmental susceptible-exposed-infectious-recovered transmission model of COVID-19 vaccination with an explicit healthcare pathway. The vaccination pathway was expanded to include booster vaccination alongside waning efficacy, capturing the “restoration of immunity” through booster doses. The new vaccination pathway was parameterised to match platform-specific vaccine efficacy data and the duration of protection.
The authors modelled the impact of the 100 Days Mission by simulating a counterfactual scenario where the global vaccination campaign began on 20th April 2020, 100 days after the publication of the full SARS-CoV-2 genome. This scenario assumes that vaccinations in each country took the same roll-out process, but 232 days earlier. Two additional scenarios reflected “increased investment” in research and delivery infrastructure.
The Manufacturing scenario removed supply constraints, enabling the rollout of vaccination on 20th April 2020 in every country, without stockouts. The infrastructure-equity scenario enhanced both national health systems and global distribution networks so that all countries achieved 40% vaccine coverage in the first year and 40% booster coverage in the second year.
To account for the relaxing of non-pharmaceutical interventions (NPIs), the authors simulated three scenarios for NPI relaxation speeds as vaccination coverage improved. The History scenario assumed no changes, whereas the Target and Economic scenarios assumed earlier relaxing; the Target scenario lifted all restrictions over two months after reaching more than 80% adult coverage in high-income countries or more than 80% coverage in those older than 60 in other countries. The Economic scenario lifted NPIs more gradually after reaching the over-60 target, prioritising the reopening of schools.
Study findings
The results suggest that the 100 Days Mission could have averted an additional 8.33 million deaths due to COVID-19 by the end of 2021 when combined with the History NPI lifting scenario. In this scenario, an estimated 26.72 million severe cases of COVID-19 requiring hospitalisation and 1/44 billion infections would have been averted. Most of these averted deaths, hospitalisations, and infections would have occurred in low- and middle-income countries (LMICs).
The estimated VSLs (value of a statistical life) that could have been saved by the 100 Days Mission through the History scenario is US$22.61 trillion globally. As VSLs are “significantly higher” in HICs, 57% of the global value of statistical life averted occurred in HICs, even though most deaths would have been averted in LMICs. To estimate the monetary values associated with lives saved the authors multiplied the number of lives saved by the country-specific monetary VSL and by the value of a statistical life-year (VSLY).
“Increased investment in both global manufacturing and health systems infrastructure further increases the number of deaths that could be averted and the associated health-economic savings.”
In the 100 Days Mission with both manufacturing and health systems investments, an estimated 11.01 million deaths could have been averted and a value of $31.29 trillion in statistical lives saved. However, the authors describe this scenario as “unlikely”. In all scenarios involving the relaxing of NPIs thanks to earlier availability of vaccines, additional lives would have been saved.
In the Target NPI lifting scenario, an estimated 5.76 million deaths (100 Days Mission alone) to 9.20 million deaths (100 Days Mission with both manufacturing and infrastructure investments) could have been averted. In these scenarios, 12,600 and 23,900 fewer days of NPIs would have been implemented globally: 70 days and 133 days on average per country. Under the Economic scenario there were “similar trade-offs between public health and economic gains”. The public health and health economic outcomes would be greater than under the Target scenario, but still lower than the History scenarios.
Substantial benefits
“Earlier access to COVID-19 vaccines could have had substantial benefits.”
Most of the estimated averted deaths would have been concentrated in LMICs, but this demands investments in vaccine research, supported by “improvements to manufacturing and health system infrastructures”. With these investments, the authors estimate that 11 million deaths could have been prevented globally.
Although NPIs were effective at reducing transmission they incurred “significant economic and societal costs”, including consequences for education. Therefore, a major benefit of earlier access to vaccination is the reduction in school closures; in the Economic scenario, prioritising school opening could have averted 1,120 weeks of full school closures and 2,490 of partial school closures. This represents an average of 6 weeks of fully open schools and 14 weeks of partly open schools per country.
“Reopening schools and relaxing NPIs safely will crucially require scaling up both vaccine delivery infrastructure and manufacturing. Without addressing both aspects, advancements in vaccine development speed might not translate into equitable benefits globally.”
The results emphasise the importance of investments in support of the 100 Days Mission in controlling a future potential pandemic, with benefits for both health and economy.
“The 100 Days Mission is ambitious, requiring global innovation through creating vaccine libraries, clinical trial networks, accelerated immune response marker identification, rapid vaccine manufacturing, and strengthened global disease surveillance.”
CEO of CEPI, Dr Richard Hatchett, hopes that this research will encourage global commitment to the 100 Days Mission.
“This work shows in the starkest terms why the world needs to be prepared to move faster and more equitably when novel pandemic disease threats emerge. Investing in preparedness now to make the 100 Days Mission possible for future incipient pandemics will save millions upon millions of lives and protect the global economy against catastrophic losses.”
Join us at the Congress in Barcelona this month to explore how lessons from the COVID-19 pandemic can inform better global preparedness for pandemic and epidemic pressures, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Oct 16, 2024 | Technology |
CEPI announced in October 2024 that it is working with experts at the National Research Council of Canada (NRC) to bioengineer a “commonly used approach” to safely make protein antigens in “as little as two weeks”. This would be between eight and twelve times faster than the current timeline of antigen production for protein-based vaccines. CEPI is contributing up to CAD $850,000 and the NRC is providing up to CAD $308,000 (in kind) to establish proof-of-technology.
Low cost and high speed
CEPI notes the importance of manufacturers being able to make “sufficient quantities” of vaccine components at low cost to enable mass production. Although mammalian cell lines are a common choice for vaccine processes, boasting ease of culture and a high production yield, they can take four to six months to develop and optimise for antigen production. This is a “major challenge” to efforts to develop vaccines quickly in response to fast-spreading viral outbreaks.
An optimised approach
Scientists at the NRC have developed a mammalian cell line that could be optimised for rapid antigen production. The research is expected to “majorly accelerate” the time needed for infectious disease vaccine development, says CEPI’s Executive Director of Manufacturing and Supply Chain (Acting), Ingrid Kromann.
“If successful, this optimised cell line could help vaccine doses be more rapidly available for clinical trials and initial emergency use during future outbreaks, supporting CEPI’s goal – embraced by Canada, and other G7 and G20 nations – to respond to a novel virus with a new vaccine in just 100 days after its discovery.”
Importantly, the technology is going to be suitable for transfer to low- and middle-income countries, enabling “local and rapid” vaccine production closer to the source of a future outbreak and improving accessibility. Dr Lakshmi Krishnan, Vice President of Life Sciences at the NRC, looks forward to working with CEPI to take the platform technologies forward to “accessible tools that could help accelerate vaccine production around the world”.
“Recognising the critical need for rapid vaccine production during a health emergency, this research and development project in our labs will advance innovative technologies to improve biomanufacturing processes and increase the efficiency of large-scale manufacturing of vaccines and other biologics.”
For the latest in vaccine technology for improved accessibility, join us at the Congress in Barcelona this month, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Oct 14, 2024 | Global Health |
In October 2024 the European Investment Bank (EIB Global) announced €2 million financing for early-stage vaccine development in Rwanda by Akagera Medicines Africa Limited. The support is intended to accelerate research, development, and manufacturing of new vaccines against infectious diseases like tuberculosis, HIV, Lassa fever, and Ebola. It will also be used to “strengthen technical skills and expertise” to support “home-grown discovery, manufacturing, and development of vaccine delivery systems” in Rwanda.
Global Gateway
This financing is part of the EU Global Gateway initiative, a strategy to “boost smart, clean, and secure links in digital, energy, and transport sectors and to strengthen health, education, and research systems”. Team Europe is mobilising up to €300 million between 2021 and 2027 to “allow EU’s partners to develop their societies and economies” whilst creating opportunities for EU Member States to “invest and remain competitive”. EIB Global supports “high impact investment” to enhance healthcare and pharmaceutical manufacturing, encourage greater “health resilience”, and support equitable access to healthcare.
Continent-based solutions
EIB Global states that Africa bears the highest disease burden globally, demanding “more home-grown or continent-based solutions”.
“Vaccination is a critical activity to ensure and guide investments in universal health and has a crucial role to play in achieving 14 of the 17 United Nations Sustainable Development Goals.”
Akagera Medicines was founded in 2018 and registered a 100%-owned subsidiary in Kigali in 2022. Its mission is “targeting tuberculosis and other infectious diseases with liposomal nanotherapeutics”. Commenting on the financing announcement at the World Health Summit in Berlin, Chief Executive Officer Michael Fairbanks recognised the “significant support” of the European Investment Bank.
“We are now a clinical company and moving faster to build human capacity and specialised infrastructure in Africa to support vaccine development.”
CEO of the Rwanda Social Security Board (RSSB) Regis Rugemanshuro stated that the financial support is an “important contribution to the realisation of Rwanda’s vision to become a biotech hub” and the wider vision of “Africa becoming self-reliant in vaccine and medicine manufacturing”.
“RSSB is looking forward to deepening partnerships with EIB and other international institutions to build resilient healthcare ecosystems in Rwanda and in Africa.”
Vice President of EIB Thomas Ostros identified the Bank’s “close cooperation with public and private partners” to “accelerate development of innovative solutions”.
“The EIB is committed to further strengthening our partnership with local and international players, to scale up investment and support innovative technology together.”
Belen Calvo Uyarra, EU Ambassador to Rwanda, agreed that the investment was another “important milestone”.
“Through Global Gateway, the EU is focussed on advancing equitable access to health products and local manufacturing in Africa.”
For more from key players in efforts to establish local manufacturing capacities in Africa and champions of equitable access to health products, join us at the Congress in Barcelona later this month. Don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Oct 11, 2024 | Technology |
CEPI announced in October 2024 that the Centre for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota is to receive US$3.2 million to advance its open access Coronavirus Vaccines Research and Development (R&D) Roadmap. This is an “important tool created to guide the development of vaccines” against multiple coronaviruses. CIDRAP will monitor and evaluate R&D progress and “catalyse efforts” to develop broadly protective vaccines. The investment from CEPI will monitor progress towards the roadmap goals and milestones and enable the creation of an online database of current literature and reports on coronavirus vaccine research.
The CIDRAP roadmap
CIDRAP’s roadmap is developed with guidance from over 50 scientific leaders and financial support from The Rockefeller and Gates Foundations. It aims to respond to the threat of coronaviruses, highlighted in the experience of three new coronavirus epidemics (SARS, MERS, COVID-19) in just 20 years. Coronaviruses are a “real and present threat” that demand a “large, comprehensive, and coordinated” initiative.
“The ultimate goal of developing broadly protective coronavirus vaccines is therefore multi-faceted: to create more efficacious and durable COVID-19 vaccines, mitigate the potential threat of future coronaviruses that have not yet emerged, and, ideally, prevent infections and transmission.”
The roadmap covers five topic areas each with “key barriers and knowledge gaps” and corresponding “technical milestones for measuring success”:
- Virology applicable to vaccine R&D
- Immunology and immune correlates of protection
- Vaccinology
- Animal and human infection models for coronavirus vaccine research
- Policy and financing
CEPI’s support
The funding contributes to monitoring progress on these goals and milestones and supports an open access online research database as well as an open access online summary of all broadly protective coronavirus vaccines in preclinical and clinical development and a dashboard tracking funding and investment.
Dr Michael Osterholm, Regents Professor and Director of CIDRAP recognised CEPI’s contribution to coronavirus vaccine research and development.
“CEPI’s support and collaboration with CIDRAP will fast forward our efforts at creating broadly protective coronavirus vaccines.”
Dr Kent Kester, Executive Director of Vaccine R&D, CEPI, commented that COVID-19 was the “third new coronavirus to strike in the past 20 years, portending the emergence of further novel coronaviruses”.
“Having the latest information on vaccine research and progress within coronavirus vaccine R&D readily and openly available in CIDRAP’s roadmap will enhance the approach being pursued by CEPI and other scientific investigators around the world to develop vaccines that could confer protection against multiple coronaviruses at the same time.”
For the latest coronavirus vaccine research updates, including insights into the challenges of universal vaccine development, join us at the Congress in Barcelona this month. Don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Oct 11, 2024 | Technology |
Orlance, Inc., announced in October 2024 that it has been awarded a National Institutions of Health (NIH) Fast Track Small Business Innovation Research (SBIR) grant to develop an Enhanced Seasonal Influenza Vaccine that provides “better protection against disease” even in years when there is a mismatch between predicted and actual circulating strains. The award includes $300,000 for Phase I; the total funding for the Phase I and II combined programme amounts to $3.3 million. The grant enables Orlance to leverage its innovative MACH-1 powdered vaccine and immunotherapy platform to address both seasonally changing and highly conserved influenza immunogens.
MACH-1 for influenza
MACH-1 is a high-performance microparticle ‘gene gun’ technology that “efficiently and uniquely” delivers DNA or RNA vaccine-coated microparticles into cells in the epidermis, which is “rich in immune stimulating cells”. An advantage of this technology in comparison with currently licensed mRNA vaccines is that MACH-1-delivered vaccines are stable at room temperature and are painless and needle-free. These vaccines also offer protective levels of immunity with the “smallest doses yet achieved within the field”.
The grant will enable a project to address the limitations of current flu vaccines by broadening the number of influenza strains targeted in one vaccine. This means vaccine production can occur closer to influenza season and achieve a better match between predicted and actual circulating strains. It will also stimulate “more diverse types of immune responses” in systemic and localised cells. The programme builds on Orlance’s universal influenza vaccine, adding seasonally changing influenza antigens to maximise protection.
Excelling in the field
Orlance’s Head of Research and Development and Principal Investigator Dr Kenneth Bagley commented on the importance of the MACH-1 technology.
“The unique properties of MACH-1 delivery into the highly immune competent epidermis that generates potent systemic and local respiratory mucosal antibody- and T cell-mediate immunity, coupled with the large payload capacity of DNA vaccines, may allow for Orlance’s universal influenza vaccine to excel where other universal vaccines have failed.”
Kristyn Aalto, CEO of Orlance, recognised the “continued funding support” from NIH.
“[The] support of the MACH-1 platform including this enhanced seasonal influenza vaccine reinforces the potential impact and significant step forward MACH-1 can bring to vaccine technology.”
We welcome Kristyn to the Congress in Barcelona this month for the Mucosal and Alternative Delivery workshop; get your tickets to join us for this here, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Oct 11, 2024 | Global Health |
A WHO report in October 2024 suggests that vaccines against 24 pathogens could reduce the number of antibiotics needed by 22% every year. Some of these vaccines are already available but currently underused, but others will need to be developed and brought to market. The report expands on a WHO study from 2023, estimating that some vaccines already in use could avert up to 106,000 deaths caused by AMR each year. Director-General Dr Tedros Adhanom Ghebreyesus highlighted that addressing AMR “starts with preventing infections”, for which vaccines are “among the most powerful tools”.
“Prevention is better than cure and increasing access to existing vaccines and developing new ones for critical diseases, like tuberculosis, is critical to saving lives and turning the tide on AMR.”
The burden of AMR
Antimicrobial resistance (AMR) is the result of bacteria, viruses, fungi, and parasites changing to stop responding to medicines. As medicines become ineffective, infections become harder to treat, which increases the risk of disease spread, severe illness, disability, and death. The report introduces the significant global burden of AMR. In 2019, an estimated 7.7 million deaths were associated with 33 bacterial infections, with almost 5 million of these associated with AMR.
The mortality burden of these drug-resistant infections is “most pronounced” on the African continent, followed by South-East Asia and Eastern Europe. However, community mobility increases the risk of transmission to other continents. AMR has the potential to impose an annual global cost of up US$3.4 trillion by 2030, with the most severe consequences for low- and middle-income countries (LMICs).
A “key driver’ of AMR is the “systematic misuse and overuse” of antimicrobials in healthcare, animal health, and agriculture; the greatest contributor to overall use of antimicrobials is use in animals. The World Organisation for Animal Health (WOAH) estimated that 84,500 tonnes of antimicrobials were used in the animal sector in 2019. However, this is a 13% decrease from 2017. On the other hand, global antibiotic consumption in humans increase by 65% between 2000 and 2015 and is projected to triple (from 2015) by 2030.
One of the major challenges is ensuring equitable access to antimicrobials, particularly in LMICs, where “people are more at risk of dying from a lack of access to appropriate antimicrobials than from resistant infections”. Managing AMR demands both sector-specific and “One Health” approaches. Vaccines can be critical to efforts to lower the burden by reducing the incidence of drug-sensitive and drug-resistant infections, antibiotic use, and opportunities for evolution and transmission of resistant genes and pathogens.
The report
Although we know that vaccines are important aspects of the solution, their specific role in reducing AMR has not been “systematically evaluated and quantified”. Therefore, the latest report evaluates this and provides recommendations for “enhancing the impact of vaccines on AMR”. It covers 44 vaccines targeting 24 pathogens, drawing the characteristics of each vaccine from various sources. Three criteria were considered:
- The AMR-related health burden – measured by the reduction in deaths and DALYs associated with AMR
- Antibiotic use (or antimicrobial use in the case of Mycobacterium tuberculosis)
- The economic burden of AMR, including hospital costs and productivity losses
Highlights from the report
- Vaccines against 16 bacterial pathogens may prevent 510,000 deaths and 28 million DALYs associated with AMR.
- This prediction increases to include an additional 1.2 million deaths and 37 million DALYs when the use of vaccines is expanded to target all populations at risk of infection.
- The non-serotypespecific vaccine against S. pneumoniae, with increased efficacy against lower respiratory tract infections, would have the highest impact on both AMR-associated deaths and DALYs.
- The greatest impact of vaccines on reducing the burden of bacterial AMR in 2019 was in the WHO African Region, averting an estimated 170,000 deaths and 12 million DALYs annually.
- In the WHO South-East Asia Region, vaccines were estimated to have prevented 160,000 deaths and 7.5 million DALYs annually.
- The development and optimal use of vaccines against 23 pathogens could avert up to 2.5 billion defined daily doses a year, which is 22% of the global estimated antibiotic use in humans associated with treating these pathogens.
What’s next?
The authors suggest that the role of vaccines in addressing AMR is “often overlooked” in policy and decision-making processes. They highlight the need for “greater recognition and integration” of vaccines into AMR mitigation strategies and the importance of considering AMR in vaccine decision-making.
“To achieve appropriate inclusion of vaccines in the AMR agenda, the immunisation and AMR communities must strengthen their joint understanding of the evidence and enhance collaboration.”
How do you think that AMR priorities can be incorporated into vaccine development and deployment efforts? Join us for the AMR and bacterial vaccines track at the Congress in Barcelona this month to contribute to these conversations, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Oct 7, 2024 | Global Health |
A week after the declaration of a Marburg outbreak in Rwanda in September 2024, Sabin Vaccine Institute announced that it is providing doses of its investigational Marburg vaccine to support the outbreak response. An initial shipment of approximately 700 doses will be used in a trial involving frontline workers, including healthcare professionals, who have been the “hardest hit” by this outbreak. Sabin and the Rwanda Biomedical Centre have entered a clinical trial agreement for a Phase II rapid response open label study, which will be conducted at six trial sites in Rwanda. Sabin also plans to supply additional vaccines, pending a request from Rwandan officials and authorisation from BARDA.
Responding to the outbreak
The outbreak was declared on 27th September 2024, and by 6th October it had caused 12 deaths. Many cases are among health workers in two facilities in Kigali, but there are more cases spread across other districts. Sabin has been “working directly” with Rwandan officials and partners to support the response. There are no licensed vaccines or treatments for Marburg, but Sabin’s single-dose vaccine is in Phase II trials in Uganda and Kenya, with no safety concerns reported to date. The vaccine is based on the ChAd3 platform and results from Phase I clinical trials and nonclinical studies suggest that it is safe and elicits “rapid” and “robust” immune responses.
Commenting on the support from Sabin, Rwanda’s Minister of Health Dr Sabin Nsanzimana reflected that “in emergency situations, the success of clinical trials relies on quick, strategic global partnerships” that combine “expertise, resources, and innovation”.
“Today, a week after this Marburg outbreak was first confirmed, we are receiving doses of the Sabin Vaccine Institute’s Marburg vaccine candidate to protect our health workers and other high-risk groups, and also advance scientific tools which will ensure this virus can be effectively controlled now and in the future.”
Lightning speed
Sabin’s Chief Executive Officer Amy Finan described the team’s “lightning speed” in responding to the Rwandan government’s request for assistance, preparing shipments, finalising protocols, and securing regulatory and legal approvals.
“This swift emergency response demonstrates that a dedicated, collaborative group of individuals and organisations can achieve remarkable results when united by a common cause: to contain a lethal disease outbreak and prevent further loss of life.”
ReiThera, Sabin’s manufacturing partner, has produced the drug substance and filled and finished doses for shipment. CEO Stefano Colloca stated that the ReiThera team believes in the “transformative power of global collaboration to advance science and create lasting impact”.
“Our partnership with Sabin highlights our shared commitment to developing a life-saving vaccine against Marburg disease with a mutual goal: to save lives and ensure that even the most vulnerable communities around the world have access to vital and equitable protection.”
Sabin’s vaccine progress
Sabin plans to launch a Phase II trial of the Marburg candidate in the United States next year, as it looks forward to interim results from the trial in Uganda and Kenya. The development programme is supported by BARDA, which has committed $235 million for advancing vaccine research and development against Sudan ebolavirus and Marburg virus diseases.
To join discussions about safety and effectiveness evaluations of vaccines deployed in emergency situations, get your tickets to the Congress in Barcelona this month. Don’t forget to subscribe to our weekly newsletters for vaccine updates.
by Charlotte Kilpatrick | Oct 4, 2024 | Technology |
In September 2024, Vaxart announced the initiation of the sentinel cohort of its Phase IIb clinical trial evaluating the oral pill COVID-19 vaccine candidate in comparison with an approved mRNA vaccine. The funding is now approved for this part comprising 400 participants; 200 will receive Vaxart’s COVID-19 vaccine candidate and 200 will receive the approved mRNA vaccine comparator. The full trial will measure efficacy for symptomatic and asymptomatic disease, systemic and mucosal immune induction, and the incidence of adverse events.
Changing the vaccine landscape
Vaxart states that “for two hundred years vaccines have been administered by intramuscular injection”, offering the company’s oral pill vaccines as a way to “change everything”. The COVID-19 vaccine attacks invading pathogens at their points of entry, triggering strong IgA and T-cell responses to “repel and overwhelm” the invaders. It is designed to be stable at room temperature to allow global distribution with “wide public acceptance, minimal cost, and maximum speed”.
In trial
The Phase IIb trial has two parts and will enrol healthy adults in the United States. The first part will engage 400 participants; once an independent Data and Safety Monitoring Board (DSMB) and FDA review the data from these participants, the second part will be initiated, enrolling 10,000 participants. A goal of the trial is to enrol participants “in line with U.S. demographics”, and to include at least 25% over the age of 65.
The primary endpoint is relative efficacy of Vaxart’s candidate compared to the approved mRNA vaccine for the prevention of symptomatic disease. Primary efficacy analysis will be performed after all participants have either discontinued or completed a study visit 12 months after vaccination. Funding was granted through BARDA’s Project NextGen initiative to accelerate and streamline the development of innovative COVID-19 interventions, including vaccines.
A strong step
Dr James Cummings, Vaxart’s Chief Medical Officer, described the initiation of the sentinel cohort as a “strong step” towards the goal of “developing a vaccine that may bring us closer to a sustainable solution to the persistent threat of COVID-19″.
“We continue to progress toward our goal of conducting the Phase IIb study and look forward to the results of our mucosal technology’s first head-to-head comparison against an approved mRNA vaccine for this virus.”
We look forward to learning more about the vaccine’s progress from Dr Cummings at the Congress in Barcelona this month; if you’d like to join us there do get your tickets now. Don’t forget to subscribe to our weekly newsletters for more updates!
by Charlotte Kilpatrick | Oct 4, 2024 | Global Health |
The University of Oxford announced in October 2024 that scientists working on ‘OvarianVax’ a vaccine to encourage the immune system to “recognise and attack” the earliest stages of ovarian cancer, have secured funding from Cancer Research UK. The team will receive up to £600,000 over the next three years to support research from establishing targets to possible clinical trials. Although getting a vaccine to the point where it is “widely available to women at risk of ovarian cancer” is “many years” away, the funding is an “exciting step” towards preventing ovarian cancer at an early stage, rather than treating it after it has taken hold.
Ovarian cancer
Ovarian cancer is the 6th most common cancer in women, causing around 7,500 new cases every year in the UK. There is currently no screening programme for the disease, and some women with are at higher risk with inherited copies of altered genes. Compared to women without gene alterations, women with altered BRCA1 genes face a higher risk by up to 65%, and women with altered BRCA2 genes face a higher risk by up to 35%.
Women with these alterations are recommended to have their ovaries removed by the age of 35, which has implications for having children and brings on early menopause. Many cases of ovarian cancer are only identified at a late stage. Professor Ahmed Ahmed is the Director of the Ovarian Cancer Cell Laboratory, MRC Weatherall Institute of Molecular Medicine at the University of Oxford, and lead for the OvarianVax project and comments that “we need better strategies to prevent ovarian cancer”.
“Currently women with BRCA1/2 mutations, who are at very high risk, are offered surgery which prevents cancer but robs them of the chance to have children afterwards.”
However, a possible “solution” could be on the horizon with the OvarianVax project, focussed on women at high risk but with potential to expand if trials are successful.
“Thanks to this funding, our research can take a big step forward towards a viable vaccine for ovarian cancer.”
Vaccine development
The researchers will identify the proteins on the surface of early-stage ovarian cancer cells that are most strongly recognised by the immune system and work out how effectively the vaccine kills organoids, “mini-models” of ovarian cancer. If this proves successful, they will move forward to clinical trials in the hope that one day women could be offered the vaccine to prevent ovarian cancer.
“Teaching the immune system to recognise the very early signs of cancer is a tough challenge. But we now have highly sophisticated tools which give us real insights into how the immune system recognises ovarian cancer.”
Professor Ahmed’s team has already found that immune cells from patients with ovarian cancer can “remember” the tumour. They will use this discovery to train the immune system to recognise over 100 proteins on the surface of ovarian cancer, known as tumour-associated antigens. The research will uncover which antigens trigger the immune system to recognise and kills cells that are becoming ovarian cancer, using tissue samples from the ovaries and fallopian tubes of people with ovarian cancer to recreate the early stages of disease.
The team will also work with patient and public representatives to understand who would be willing to take the vaccine, who would receive the most benefit from it, how it could be administered, and how to ensure it is taken up by as many eligible women as possible if it is successful in clinical trials.
Prevention research strategy
This is one of several projects that Cancer Research UK is funding within its prevention research strategy, which seeks to use discoveries from the lab to find more precise ways to prevent cancer. Cancer Research UK’s Chief Executive, Michelle Mitchell, described these projects as “a really important step forward into an exciting future, where cancer is much more preventable”. The funding should “power crucial discoveries” that can be used to “realise our ambitions to improve ovarian cancer survival”.
“OvarianVax builds on the exciting developments in vaccine technology during the pandemic. This is one of the many projects which we hope will give women longer, better lives, free from the fear of cancer.”
For more on using the latest lab discoveries to improve patient outcomes with vaccines, get your tickets to the Congress in Barcelona this month, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Oct 2, 2024 | Global Health |
In October 2024, CEPI announced the expansion of research into Lassa fever in West Africa in a “pioneering study” to explore the variation in disease symptoms and how this compares to other “worrisome infections” in the region. The project, led by the Nigeria Centre for Disease Control and local study sites, comes under the Enable study, created by CEPI and partners to provide a more accurate picture of the disease burden in West Africa and help inform outbreak preparedness efforts, including Lassa vaccine development. Lassa fever, a known public health burden in the region, infects “hundreds of thousands” every year. However, cases are likely underreported due to detection difficulties.
Lassa fever
Although it was described in the 1950s, the virus causing Lassa fever was only identified in 1969. It is a single-stranded RNA virus in the Arenaviridae family. The disease is a “potentially deadly haemorrhagic illness” with an estimated 1% case fatality rate. Most infections are thought to be “minimally symptomatic or asymptomatic”, which means they avoid detection. People who do experience symptoms can suffer fever, headache, and chills, and could be misdiagnosed with diseases like Ebola, dengue, or malaria.
As a WHO priority disease, Lassa fever is in “urgent need” of research and development. Understanding the disease is critical to vaccine development, which Dr Muhammad Ali Pate, Coordinating Minister of Health and Social Welfare of Nigeria, recognises.
“Lassa fever remains a public health burden in Nigeria and West Africa, but the commitment to research and innovation is yielding promising progress. The new Enable research will deepen our understanding of the virus and enhance the work being undertaken to develop the first-ever Lassa vaccine to safeguard the health of our communities.”
Dr Pate highlighted the Ministry’s commitment to collaboration to “advance these efforts and bring the suffering caused by Lassa fever to an end”.
Enable expanded
Enable was launched in 2019, and in 2021 CEPI announced funding to provide a “more accurate assessment” of the incidence of Lassa fever infections. CEPI offered US$ 10.3 million to partners in Benin, Guinea, Liberia, and Sierra Leone to participate, enrolling up to 23,000 participants to understand the “rate, location, and spread of Lassa virus across the region”. The results are also central to CEPI’s goal of producing a licensed Lassa vaccine.
The new year-long study will invite 5,000 healthy people, including children and infants, to participate at sites in Nigeria (Edo, Ondo, and Ebonyi states), Sierra Leone, and Liberia. It is intended to improve understanding on how commonly the disease occurs, how rates of infection and symptoms vary across locations, ages, sex, and exposure history, and the extent of post-infection symptoms. Scientists will also explore how often people are co-infected with Lassa fever and malaria, as co-infections may complicate the clinical course of each disease.
Vaccine goals
Dr Richard Hatchett, CEO of CEPI, explained that “incomplete detection” of cases affects both the understanding of the true incidence rate and level of response, but could also “threaten the evaluation, rollout, and acceptance of future Lassa vaccines”.
“Insights gained on the diversity of disease symptoms will enhance our understanding of Lassa fever, categorised into mild, moderate, or severe cases. This information will be crucial in guiding where and how future late-stage vaccine trials are conducted and determining priority groups for receiving the Lassa vaccine once it becomes licensed in the coming years.”
A 2024 modelling study found that around 3,300 lives could be saved over 10 years with a Lassa vaccine. It could also avert up to $128 million in societal costs. The most advanced vaccine candidate is developed by IAVI and is currently in Phase II trials in the region. Enable National Project Coordinator in Nigeria, Mrs Elsie Ilori, described the launch of the expanded study as a “key step in our ongoing efforts to understand and combat this dreadful disease”.
“Through deeper investigations into the variations of Lassa fever symptoms and their comparison to other infections within the region, we will obtain valuable insights that can improve diagnosis, boost outbreak preparedness, and inform the future vaccine development.”
Dr Jilde Idris, Director General of Nigeria Centre for Disease Control and co-chair of the Nigeria Lassa Vaccine Task Force agreed that the investigation “represents key progress in our battle against Lassa fever”.
“We are improving our capacity to identify and recognise cases while preparing for future vaccine development by examining the disease’s symptoms and its connection to other infections.”
The work is “vital for forming health practices” and “promoting” public health in the region, and Dr Idris welcomed the support of partners and local communities in “making strides towards lessening the impact of Lassa fever” and preparing for a “future that can block its life-threatening effects”.
For more on IAVI’s vaccine efforts and insights into challenge studies in West Africa, join us at the Congress in Barcelona this month for a session with Dr Marion Gruber. Don’t forget to subscribe to our weekly newsletters here for vaccine updates!
by Charlotte Kilpatrick | Sep 30, 2024 | Global Health |
The University of Connecticut announced in September 2024 that a $3.8 million R01 grant from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), will support efforts to develop universal vaccine candidates for leptospirosis. Assistant Professor Elsio Wunder, from the Department of Pathobiology and Veterinary Science in the College of Agriculture, Health, and Natural Resources (CAHNR), will work with colleagues to tackle the animal-borne disease. Leptospirosis is a “neglected disease” with no worldwide approved vaccine.
Leptospirosis
Leptospirosis is a disease caused by the Leptospira bacteria, found in contaminated water or soil. It affects animals and people, and if left untreated in humans can lead to kidney damage, meningitis, liver failure, breathing difficulty, or death. An estimated 1 million human cases occur globally each year, causing around 60,000 deaths annually. The disease is considered “neglected” because it “typically impacts poorer communities and individuals who lack access to adequate sanitation”. Neglected diseases tend to receive less attention and funding than other diseases. However, researchers like Dr Wunder are hoping to “correct this public health injustice”.
A big investment
Dr Wunder has a background in veterinary and human health and has focused on improving diagnostic and prevention mechanism for leptospirosis. The latest award will support these efforts.
“It’s a big investment from the NIH. I’m very grateful. The fact that you have this major investment in a neglected disease is a really big step.”
The team involves researchers from Yale University, the University of California-Irvine, and Serimmune, bringing “strong and diverse expertise” from various fields. They will spend five years developing vaccine candidates and testing them in animal models, hoping to find a viable candidate that is ready for testing in human clinical trials.
Universal focus
The project focuses specifically on developing a universal leptospirosis vaccine, which could be used in “any epidemiological setting in the world” and protect against disease “no matter which strain is circulating in the area”. To do this, the researchers will need to understand more about leptospirosis causing illness. Dr Wunder’s previous research produced an attenuated leptospirosis vaccine, which produces immune responses for specific strains, rather than multiple variants. However, the work behind this vaccine revealed that the bacteria’s proteins are a key target.
In the new project, Dr Wunder and collaborators will pursue a multi-recombinant protein vaccine. Vaccine development for leptospirosis is “very hard” and bacteria have “so many tools to evade host immune defences”. Therefore, the researchers have tried to use several proteins at once. The goal is to create a vaccine with small and relevant elements of these recombinant proteins and ensure that the vaccine can be produced and distributed cheaply. This would enable the best public health effect for people who suffer the greatest burden of the disease. Alongside the project, Dr Wunder will maintain his research and teaching at CAHNR.
“I teach a class that’s an introduction to pathobiology and a mix of basic and translational research, and how important translational research is to improve life for people – in terms of vaccines, treatments, and diagnostics. But in order to have translational research, you do need basic science. And this grant is very much a mix of both.”
For insights from leaders in ‘neglected disease’ research at the Congress in Barcelona next month, get your tickets to the event here, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Sep 26, 2024 | Global Health |
A $4.2 million Programme Project Grant renewal from the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) in September 2024 will fund efforts by researchers at Weill Cornell Medicine to develop a cytomegalovirus (CMV) vaccine. The vaccine is intended to prevent the transmission of cytomegalovirus from mother to baby during pregnancy. The grant could be extended for five years and $20.4 million to enable research to accelerate the vaccine’s development.
Protecting the foetus
Cytomegalovirus (CMV) is the most common congenital infection worldwide, but Dr Sallie Permar, chair of the Department of Paediatrics at Weill Cornell Medicine, hopes to find a vaccine that prevents transmission of the virus to the developing foetus. Around 1 in 200 babies is born with CMV, with one-quarter of them experiencing long-lasting effects such as hearing loss, microcephaly, developmental delays, and seizures. Dr Permar compares the effects to those recognised in the Zika epidemic, commenting that CMV “affects ten times as many infants”.
“If we could eliminate this terrible congenital infection, we would give more babies the chance to achieve their full potential in life.”
A model of transmission
More than half of all adults live with CMV, but if it is acquired for the first time during pregnancy, the mother has a 30% to 40% chance of passing the virus to her baby. As it is “challenging” to design a clinical trial large enough to assess the effectiveness of a CMV vaccine to protect the foetus, Dr Permar has created a collaborative network. With researchers at the University of California Davis Primate Centre, Tulane University, and Oregon Health Sciences University (OSHU) and Primate Centre, Dr Permar has developed a non-human primate model of congenital CMV transmission to test vaccines.
“This work requires a cadre of multidisciplinary virologists, immunologists, pathologists, physicians, and veterinary scientists who all care deeply about eliminating this devastating childhood infection through vaccination.”
Tackling “immune-evading tactics”
Dr Permar states that CMV has “multiple strategies” for evading host immunity; the virus conceals itself in a person’s cells and producing factors to catch host antibodies, disable common killer T cells, and cause confusion for the antiviral immune response. With the latest grant renewal, the researchers will explore approaches for “thwarting these viral immune-evading tactics”.
The team will use weakened viruses and some of the virus’ own protein factors as antigens to induce the production of antibodies against “CMV’s evasive manoeuvres”. They hope to have a prototype for a vaccine in five years, at which point they could advise the industry on vaccines that are currently in clinical trials.
For insights into maternal vaccine challenges and strategies at the Congress in Barcelona next month, get your tickets to join us here, and don’t forget to subscribe to our newsletters for regular vaccine news.
by Charlotte Kilpatrick | Sep 26, 2024 | Global Health |
In September 2024 Africa CDC and IAVI announced the signing of a Memorandum of Understanding (MoU) to enhance the continent’s capacity to fight disease, pandemic readiness, and supply resilience. This will involve expanding capabilities for locally driven research, development, manufacturing, and supply of priority vaccines and antibodies as well as strengthening Africa CDC-led initiatives. The partnership will combine IAVI’s “expertise in vaccine and antibody development and access” and the “extensive network and Africa CDC”.
Initiatives under the MoU
The MoU is intended to tackle pressing public health challenges and promote long-term health security. Some of the key initiatives under the MoU include:
- Supporting the development of vaccines and antibodies for regional health priorities (like Lassa fever and HIV)
- Fostering a sustainable supply and demand ecosystem for priority products in the region (including monoclonal antibodies)
- Strengthening African research and development capacity
- Exploring regional stockpile strategies for licensed and investigational products to ensure rapid responses during health crises
The MoU exemplifies the “action-oriented partnerships” that Africa CDC’s New Public Health Order demands as the organisation drives its vision for “redefining global health architecture” and ensuring that Africa and the world are better prepared for future health threats. IAVI recognises the support of funders and partners, including Wellcome, CEPI, the European and Developing Countries Clinical Trials Partnership (EDCTP), the United States Agency for International Development (USAID) and the United States President’s Emergency Plan for AIDS Relief (PEPFAR) through the Accelerate the Development of Vaccines and New Technologies to Combat the AIDS Epidemic (ADVANCE) programme.
Dr Mark Feinberg, IAVI President and CEO, described the cooperation as a “key step” in IAVI’s mission to “improve global access to biomedical innovations and safeguard public health”.
“It goes beyond R&D; it’s about creating a vibrant health innovation ecosystem that meets current and future needs across Africa.”
We look forward to welcoming senior representatives of IAVI back to the Congress in Barcelona next month to learn more about the various efforts and initiatives they are enabling in pursuit of global health goals. Get your tickets to join us there and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Sep 23, 2024 | Technology |
Evaxion Biotech announced the launch of an enhanced version of its clinically validated AI-Immunology platform in September 2024, with an update to the EDEN AI prediction model. Improvements to the model include toxin antigen prediction, which enables the development of improved bacterial vaccines. AI-Immunology allows Evaxion to simulate the immune system and create predictive models to identify and develop personalised and other next-generation immunotherapies. It uses advanced AI and machine learning technologies to design and develop vaccine candidates in response to significant unmet needs.
EDEN upgraded
The AI-Immunology platform can deliver a new target within 24 hours, with “robustly validated” predictive capabilities. The EDEN prediction model is one of five models within the AI-Immunology platform. It rapidly identifies antigens that will trigger a robust protective immune response against “almost any” bacterial infectious disease. The model is fully AI-driven and designed to identify vaccine candidates “faster and at a lower cost than current state-of-the-art methods”. EDEN enables a novel approach to vaccine development that supports efforts against the “rising global issue of antibiotic resistance”.
The latest version 5.0 features several updates:
- Novel bacterial toxin antigen predictor – Evaxion has trained new machine learning models to improve the accuracy and reliability of toxin antigen prediction.
- Expanded training dataset – The process for curating additional training data from published sources has been streamlined with retrieval-augmented generation with large language models, followed by manual domain expert curation.
- Advanced protein feature prediction – The team has developed a new building block for protein feature prediction using protein language models, enhancing the model’s architecture and capability to predict various protein characteristics.
CEO of Evaxion, Christian Kanstrup, described the launch of the model as an “important milestone” that strengthens the AI-Immunology platform.
“As one of the few truly AI-first TechBio companies, our AI-Immunology platform is at the forefront of innovation. We wil continue to invest in its development and refinement to further improve our ability to discover novel targets and develop advanced vaccines.”
We look forward to learning more about the AI-Immunology platform at the Congress in Barcelona next month; get your tickets to join us there and don’t forget to subscribe to our weekly newsletters for more vaccine technology updates.
by Charlotte Kilpatrick | Sep 19, 2024 | Technology |
An article in Scientific Reports in September 2024 uses Digital Shadows to facilitate a comparison of recombinant DNA and in vitro (IVT) mRNA vaccine manufacturing technologies. The authors offer an assessment of which manufacturing platform is better suited for two types of vaccines. They suggest that recombinant DNA technology exhibits a higher Profitability Index, but mRNA offers faster high potency in short product development cycles.
Technical and economic benefits
Limitations in “traditional vaccines” have “speared” the development of novel technologies for antigens and monoclonal antibodies, including the recent use of recombinant DNA and RNA technologies in the COVID-19 pandemic. Recombinant DNA technology requires the insertion of a gene encoding the relevant pathogen or immunoglobulin sequence into a cell factory organism, which produces the antigen or antibody. RNA technology uses stoichiometric biochemical reactions to produce mRNA (messenger RNA) encoding the antigen or antibody, which is translated in vivo by the recipient’s cells.
Both mRNA and DNA technologies have “established proof of therapeutic effectiveness”. However, they differ in approach to obtaining the therapeutic protein of choice, which leads to different manufacturing processes. For recombinant DNA, the process is “time-consuming and expensive, requiring specialised laboratory facilities and trained personnel”. By contrast, IVT mRNA is understood to be “fast, flexible, and inexpensive”. This is offset by the need for cold transportation and storage to cater to the “instability and sensitivity” of the RNA molecule. Furthermore, IVT mRNA-based vaccine manufacturing has not been standardised.
Both technologies have “captured the global scientific interest” and present opportunities in the treatment of cancer and autoimmune diseases among others. However, the authors state that that there is no comparison of the two technologies on technical and economic levels.
The study
Digital Shadows are “enabling tools suitable to model a system in a fiat cyber-physical environment, delivering data flow abstractions of processing performance”. They are also used in the study to simulate and analyse the “technical merits and production costs” of each technology at given operating conditions. This allows the researchers to investigate root cause deviations and evaluate the cost-effectiveness scenarios of each proposed solution.
The authors constructed Digital Shadows to compare recombinant manufacturing of monoclonal antibodies and antigens with IVT mRNA production processes. They developed algorithmic threads to explore strengths and weaknesses, offering “enabling tools of strategic decision planning”.
The research suggests that recombinant production methods create “highly stable and therefore advantageous products”, with a proven track record of clinical safety and efficacy, and a low risk of unknown side effects, carrier-related allergic reactions, and withdrawals. The vaccines require “minimal maintenance” to preserve stability and functionality, which “ameliorates any respective logistical challenges and minimises the risks related to post-production regulatory withdrawals”. The components needed for production are “accessible” for the pharmaceutical industry but may come under pressure in case of pandemic outbreaks.
A drawback of the recombinant DNA vaccine production platform is its “complicated and therefore difficult-to-automate sub-processes”. The technology requires additional personnel for “process supervision and control purposes”. The platform is therefore “less appropriate for encountering pandemic bursts” or tracking mutations.
Another concern is the high risk of material contamination in cellular protein production, particularly in upstream processing. If contamination occurs, the cell line and its products are discarded, which causes delays and financial losses. Alongside this risk, recombinant DNA and protein production methods feature “low production yield”, which means that raw and side materials are purchased at high quantities and handled by expert personnel to reach the necessary production capacity.
IVT mRNA manufacturing protocols have “strong competitive advantages” in some characteristics. Although the vaccine is “highly sensitive to environmental conditions”, the production process is “easier to standardise, automate, adapt, and operate in continuous mode” thanks to the synthetic chemical nature of its sub-processes. The biochemical section of related processes can offer a “less complex, more effective” alternative with minimal requirements. This reduces the risks of cross contamination and quality-related batch rejections, producing higher yields and limiting product losses; it also lowers raw material processing resources and reduces development time.
Conclusions
For monoclonal antibody products, the study showed that recombinant DNA technology had a higher Profitability Index than IVT mRNA manufacturing. While the recombinant DNA monoclonal antibodies require a significantly higher dose due to an inferior potency profile, this is not reflected analogously in the final production cost. IVT mRNA manufacturing also had “higher dependencies” on raw materials.
When considering antigenic vaccines, the authors found that recombinant DNA technology demonstrated “higher economic performance”, demanding reduced capital resources. It also encompasses “proven, well-grounded protocols” for process development. Recombinant manufacturing “appears advantageous” by meeting technical and financial expectations. However, IVT mRNA “significantly” shortens the timeline from development to clinical application and benchtop to scale manufacturing. It also offers “unparalleled advantages” in synthetic processes and reduced requirements for installing large-scale production equipment.
The paper concludes that clinical trials and field practice will reveal if mRNA technologies can offer non-inferior therapeutic results compared to their DNA recombinant established alternatives. If you have worked with either of these technologies, what are your impressions or predictions? Why not join us at the Congress in Barcelona next month to share your insights into various platform technologies, and don’t forget to subscribe to our weekly newsletters for the latest vaccine news.
by Charlotte Kilpatrick | Sep 18, 2024 | Technology |
PharmaJet announced in September 2024 that it has entered a long-term license and supply agreement with Scancell Holdings to use PharmaJet’s Stratis Intramuscular (IM) Needle-free System for the delivery of its advanced melanoma DNA vaccine. Through the agreement, Scancell will use Stratis for the clinical development and commercialisation of ImmunoBody, the advanced melanoma DNA vaccine. PharmaJet will receive development and regulatory milestone payments and royalties on net sales upon commercialisation.
Stratis
PharmaJet’s Stratis technology is a needle-free system for 0.5 ml intramuscular and subcutaneous injections that enhances the performance of nucleic acid vaccines and therapeutics. Stratis delivery has demonstrated the ability to enable “effective uptake” of the Scancell DNA melanoma vaccine; 60 patients across 15 clinical trial sites have received a total of 171 doses of SCIB1/iSCIB1+ through Stratis. This approach offers the “convenience of an off-the-shelf therapeutic cancer vaccine with the speed and enhanced patient experience of needle-free delivery”.
ImmunoBody vaccines
Scancell’s ImmuoBody vaccines are designed to generate “potent” T cell responses that provide a broad anti-tumour effect. They are DNA vaccines that encode a protein in antibody form, with the elements of the antibody that would normally bind to the target protein replaced with cancer antigen epitopes. ImmunoBody vaccine design features include:
- Epitopes that bind to MHC class I and MHC class II
- Retention of the Fc region of the protein, which targets activated dendritic cells via its specific receptor
However, Scancell highlights the “most important aspect” of the technology as the ability to initiate both direct and cross-presentation of epitopes to T cells. The “highest avidity T cell responses” are generated if different pathways are used to present the same epitope. In ImmunoBody, the DNA form is taken up and processed directly by dendritic cells and the protein form binds to the high affinity Fc receptor on dendritic cells, leading to cross-presentation.
Advancing innovation
Professor Lindy Durrant, Chief Executive Officer of Scancell, is pleased that PharmaJet delivery “works effectively” with the SCIB1/iSCIB1+ vaccines and offers a “well-received immunisation for patients”.
“Securing long term supply for the PharmaJet Stratis Needle-free Injection System is important to allow clinical and commercial development of iSCIB1+…Our ultimate goal for Scancell has been to deliver an off-the-shelf, safe, tolerable, effective therapy that can provide potent and durable anti-tumour responses for unresectable stage IV melanoma, which currently has a 5-year survival of 35%.”
PharmaJet’s Chief Scientific Officer, Nathalie Landry, looks forward to working with Scancell to “advance their innovation further in clinical development and commercialisation” with benefits for melanoma patients.
“The Scancell strategic partnership further solidifies PharmaJet’s commercial delivery platform as a leader in the delivery of nucleic acid vaccines and immunotherapies.”
For more on PharmaJet’s needle-free delivery technology, join us at the Congress in Barcelona next month. Don’t forget to subscribe to our weekly newsletters for regular vaccine updates.
by Charlotte Kilpatrick | Sep 17, 2024 | Technology |
Albert Einstein College of Medicine announced receipt of a five-year grant worth $14 million a year from the National Institute of Allergy and Infectious Diseases (NIAID). The grant is part of NIAID’s ReVAMPP (Research and Development of Vaccines and Monoclonal Antibodies for Pandemic Preparedness) Network. The funding will enable participation in a national effort to develop “plug-and-play” vaccines and antibody-based therapies against various emerging viruses. Albert Einstein College of Medicine will lead a consortium, called PROVIDENT (Prepositioning Optimised Strategies for Vaccines and Immunotherapies Against Diverse Emerging Infectious Threats).
PROVIDENT
The PROVIDENT consortium links 13 teams from academia, government, and industry on four projects to:
- Discover and analyse virus-host interactions and the molecular mechanisms involved in viral disease
- Design proteins to elicit antiviral immune responses and then evaluate and optimise those responses
- Create “road maps” for quick development of RNA vaccines against microbes with pandemic potential
- Map the antibody response observed in people infected with viruses for use in vaccine and therapeutic design
The project builds on NIAID’s 2021 Pandemic Preparedness Plan, which “leverages its broad research portfolio, long-standing expertise in product development, capacity to engage both domestic and international partners, and flexible infrastructure”. The plan addresses both “priority pathogens” and “prototype pathogens”.
Prototype pathogens will be PROVIDENT’s focus; these are “representative viruses” in families with potential to cause “significant human disease”. The research will concentrate on three virus families:
- Nairoviruses – transmitted by ticks
- Hantaviruses – borne by rodents and other small mammals
- Paramyxoviruses – borne by bats and other mammals
A sprint strategy
Dr Kartik Chandran, principal investigator on the grant, professor of microbiology and immunology, Gertrude and David Feinson Chair in Medicine, and Harold and Muriel Block Faculty Scholar in Virology, reflected on the importance of pandemic preparedness as revealed during COVID-19.
“One of the key lessons from the COVID pandemic is that having existing research on a viral family allows scientists to develop vaccines and therapeutics for a particular virus much more quickly. In our project, we plan to create a base of critical knowledge about a group of similar viruses and then – should a related ‘virus X’ pose a health threat – develop specific countermeasures as quickly as possible to save as many lives as possible.”
Dr Chandran explained that the researchers will select and study one or two prototype viruses from each family, developing countermeasures that will work against “as many viruses within that family as possible”.
“That strategy of quickly responding to an emerging virus with an approach and tools that have already been developed is what we mean by ‘plug and play’. A part of PROVIDENT’s strategy will be to carry out ‘sprints’ in which countermeasures that are developed for the prototype pathogens will be tested against other viruses in the same family to see how well they work and to improve them.”
The approach enabled faster development during the COVID-19 pandemic, and Dr Chandran emphasised the importance of coordinating efforts to “increase our odds of mounting a timely and effective response”. Dr Eva Mittler, research assistant professor and leader of a PROVIDENT component, warned that “we don’t know what virus will cause the next pandemic”.
“Recent outbreaks of mpox, Nipah virus, and Eastern equine encephalitis, among other viral infections, underscore the need for an even broader preparedness programme.”
To join your colleagues at the Congress in Barcelona next month and share perspectives on pandemic preparedness and innovative vaccine development, get your tickets now. Don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Sep 10, 2024 | Global Health |
The University of Oxford’s Centre for Cancer Early Detection and Prevention announced in September 2024 that Cancer Research UK has awarded a team of scientists up to £550,000 to carry out “underpinning work” to test a vaccine for patients with Lynch syndrome. Lynch syndrome is associated with a higher overall risk of developing some types of cancer. The vaccine, if successful, could protect people with Lynch syndrome before cancer begins to develop.
Lynch syndrome
A heritable genetic condition, Lynch syndrome is caused by an altered copy of a gene that is involved in processes that support DNA repair. Failure to repair DNA can cause damage to genes that control growth. This increases the risk of cancer. People with Lynch syndrome have a “higher overall risk” of developing bowel cancer and other cancers such as womb cancer (endometrial cancer) and ovarian cancer.
Up to 7 in 10 people with Lynch syndrome develop bowel cancer in their lifetime. It is estimated to cause around 3% of bowel cancer cases in the UK each year. Although between 175,000-200,000 people are estimated to have Lynch syndrome in the UK, fewer than 5% have been diagnosed.
Vaccine potential
The team at Oxford will analyse pre-cancerous cells from people with Lynch syndrome to determine which parts of a pre-cancer are potential immune targets. They will then design a vaccine that encourages the immune system to recognise pre-cancer cells and destroy them before they develop into cancer. The researchers will continue working with people with Lynch syndrome, who have helped to co-develop the project so far. They will also consult people living with Lynch syndrome to understand their views about using vaccination to prevent cancer.
Free from fear of cancer
Associate Professor David Church, Cancer Research UK Advanced Clinician Scientist Fellow and co-lead of the LynchVax team at Oxford reflects that “less than 5% of people with Lynch syndrome are aware that they have the condition”. However, “it accounts for an estimated 1,300 cases of bowel cancer and increases the risk of other types of cancer”.
“We hope our research will lay the early foundations to potentially prevent these cases through vaccination, removing the fear of cancer from people whose chances of developing it in their lifetime are far higher.”
Professor Simon Leedham, Honorary Consultant Gastroenterologist and co-lead of the LynchVax team agrees that LynchVax “has the potential” to reduce the “very high risk” of developing these cancers for people with Lynch syndrome.
“While our work is in its infancy, we are excited by the prospect of a vaccine that can potentially be used to prevent the multiple types of cancer that typically occur in people with Lynch syndrome and deliver tangible improvements in survival.”
Helen White is a member of the LynchVax patient and public involvement group and is “delighted” to be a part of developing the “potentially life-changing vaccine for people like me with Lynch syndrome”.
“As passionate advocates for involving people with lived experience in research, we fully endorse the plans to reach out to the wider Lynch syndrome community to gather their views on a cancer-preventing vaccine. This is a crucial step in preparing for future clinical trials.”
Michelle Mitchell, Cancer Research UK’s Chief Executive comments that cancer vaccines “continue to show promise in helping to create a world where people can live longer, better lives, free from the fear of cancer”.
“Projects like LynchVax are a really important step forward into an exciting future, where cancers that occur in people with Lynch syndrome could potentially be prevented. This is one of many cancer vaccine projects Cancer Research UK is funding that we hope will reduce the number of cancer cases over the coming decades.”
To hear from experts working to address various cancers with vaccines, get your tickets to the Congress in Barcelona this October. Don’t forget to subscribe for more vaccine updates every week.
