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 study in The Lancet in October 2024 finds that a single dose of typhoid conjugate vaccine (TCV) offers safe and effective protection against typhoid two years after vaccination in all children and sustained protection for older children at three to five years after vaccination. However, a “decline” in protection was observed after this period, with the greatest decline identified in children vaccinated at younger ages. The authors infer that a booster dose of TCV, perhaps around school entry age, might be needed for children vaccinated while younger than two years old, to sustain protection through the years when the risk is highest.
TCV
Typhoid fever places a “substantial disease burden” on low- and middle-income countries “marked by inadequate sanitation and limited access to clean water”. There are an estimated 7.15 million cases and 93,300 deaths each year. This burden is exacerbated by the “escalation” of antimicrobial resistance (AMR), which reduces treatment options. WHO recommends vaccines as an “important tool” in typhoid prevention and control strategies.
The first typhoid conjugate vaccine (TCV) was prequalified by WHO in 2017 based on field safety and immunogenicity data and findings from a controlled human infection model. 2-year vaccine efficacy has since been confirmed at 79-85% in randomised control trials. Research has revealed a “consistent trend” of waning protection in children vaccinated at a young age. Although WHO’s current recommendation is a single dose for infants and children from 6 months of age, epidemiological studies in countries across Asia and Africa suggest that incidence peaks in children between the ages of 5 and 9 years. Therefore, the authors identified a need to understand if a single dose of TCV can provide “substantial protection” in the medium and long term, or if a booster dose is needed.
Expanding the TyVAC trial: TyVOID
The cluster-randomise controlled trial (TyVAC) to assess the safety, immunogenicity, and protection conferred by a single dose of TCV started in Bangladesh in 2018 with a follow-up to 18 months. To generate further data, the authors extended this to evaluate vaccine protection and immunogenicity at 3-5 years after vaccination.
In TyVAC, healthy children aged 9 months to 15 years were offered TCV or a Japanese encephalitis vaccine according to their cluster of randomisation. 150 clusters were randomised to either TCV or the Japanese encephalitis vaccine, with 75 in each group. After a 3-month passive surveillance period, the baseline of TyVOID began at the final visit of TyVAC. Vaccinated children visited study clinics; after unmasking, participants in the Japanese encephalitis group were offered vaccination with a single dose of TCV, but TCV recipients were not offered the Japanese encephalitis vaccine.
Two cohorts of TCV-vaccinated children were available for follow-up:
- The group vaccinated in the original study between April 2018 and November 2019 (previous-TCV group)
- The group originally vaccinated with Japanese encephalitis and later TCV between January and August 2021 (recent-TCV group)
Results
During a median of 2.4 years, 14 episodes of typhoid fever were detected in the recent-TCV group (incidence rates of 31 per 100,000) and 45 episodes among the previous-TCV group (incidence rates of 97 per 100,000). The “significantly higher” incidence of typhoid fever in the previous-TCV group indicates a “drop in the vaccine effectiveness” 3-5 years after vaccination. The waning of vaccine effectiveness was further confirmed through the inclusion of unvaccinated children who sought care for fever as the reference group.
The decline in vaccine effectiveness correlated with age at vaccination; children in the youngest age group exhibited the most substantial reduction in vaccine effectiveness. The reason for the age-specific difference is “unclear”, but the authors suggest that underdeveloped bone marrow in younger children results in a weaker ability to support long-lived plasma cells. Another possibility is that older children have more opportunities for exposure to S Typhi than younger children, contributing to a greater durability of antibody concentrations after vaccination.
The issue of exposure is also relevant in comparing this study to a study in Malawi, as the incidence of typhoid fever in Bangladesh was “approximately three times higher”, with greatest disparity in younger children. Therefore, while a single dose of TCV might remain “highly effective” in Malawian children, it ceases to confer sufficient protection in Bangladeshi children.
“Put simply, it may be that more antibody is needed in Bangladesh to protect against typhoid fever than in Malawi as the incidence of infection is likely to be higher in Bangladesh.”
Implications
The introduction of TCV as a catch-up campaign in several countries is “likely to have a substantial impact” on the typhoid burden in these countries. TCV will then be integrated into local EPI programmes with a single dose, focussing on infants and toddlers. However, the authors urge WHO to evaluate their data and consider the “potential need for a booster around school entry age”.
Associate Professor Xinxue Liu of the Oxford Vaccine Group is one of the senior authors and emphasised how “serious and life-threatening” the disease is, particularly for “children and adolescents in low- and middle-income countries”.
“TCV offers the best chance to reduce the burden of typhoid, helping to reduce transmission and limiting further evolution of drug-resistant strains. This study provides additional information for policy makers on longer-term TCV protection and the importance of continued investigation and updated guidance.”
Dr Firdausi Qadri, Senior Scientist at the Infectious Diseases Division at the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) and first author, commented that the results “indicate a decay in antibody concentrations in different age groups”.
“[They] suggest that a booster dose around school entry age for children vaccinated while younger than 2 years could be considered, to sustain the protection from TCV through the school years when children are at greatest risk of typhoid.”
Professor Sir Andrew Pollard, Director of the Oxford Vaccine Group, reflected on WHO’s “current” recommendation.
“Epidemiological studies in different countries across Asia and Africa showed that the incidence of typhoid fever is much higher in children younger than 16 years than it is in adults, with the peak of cases seen in those aged 5-9 years. Whether a single dose of TCV provides long-term protection continues to be a top research priority to advise policy makers.”
For the latest vaccine research updates, why not subscribe to our weekly newsletters here? We hope you will also join us at the Congress in Barcelona this month to discuss vaccine questions and explore global health concerns.
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 10, 2024 | Global Health |
In October 2024, WHO announced an agreement with the International Monetary Fund (IMF) and the World Bank Group (WBG) on “broad principles for cooperation on pandemic preparedness”. The cooperation is intended to enable scaling up of support to countries to prevent, detect, and respond to public health threats through the IMF’s Resilience and Sustainably Trust (RST), WBG’s financial and technical support, and WHO’s technical expertise and in-country capabilities. The organisations will “leverage their experience to enhance pandemic preparedness”, working on the “synergies and complementarity” of each institution’s in-country analysis and operations.
Principles of coordination
Under the Broad Principles of Coordination:
- WHO and the WBG will continue to lead on health-related development policies and, with other multilateral development banks and The Pandemic Fund, on specific project investments for pandemic preparedness. RST financing will not be earmarked for specific projects.
- Pandemic preparedness policy reform measures supported by RSF arrangements will be informed by existing data, analytics, and operational engagement of WHO, the WBG, and country authorities.
- Pandemic preparedness reforms will build on each institution’s area of expertise. RSF programmes will focus on macro-critical policy reforms within the IMF’s expertise and complement the work carried out by the WBG and WHO to maximise both the financial resources and technical expertise available to countries. RSF Reform measures can include policy actions aimed at enhancing the readiness of finance and health systems to respond effectively to future health emergencies.
The cooperation will enable all three institutions to better serve countries’ efforts on pandemic preparedness.
Working for a safer world
Kristalina Georgieva, Managing Director of the IMF commented that the “stepped-up collaboration” will help the organisations to “complement and leverage each other’s expertise” to support members’ pandemic preparedness and resilience efforts.
“The IMF’s Resilience and Sustainability Trust allows eligible member countries to access affordable, long-term financing to address structural challenges that threaten their macroeconomic stability.”
WHO Director-General Dr Tedros Adhanom Ghebreyesus reflected on the need for “new sources of financing to bolster health systems”, making them “more able to prevent and detect” health threats and to “respond and withstand them when they strike”.
“WHO is proud to be working with the IMF and the World Bank to unlock financing from the Resilience and Sustainability Trust, and support countries to put it to work for a safe world.”
World Bank Group President Ajay Banga suggested that the “deepened collaboration” will focus efforts to help countries prepare for and respond to health threats.
“We must aggressively be planning and preparing for the next global health crisis, so that when the battle comes – and we know it will – we will have the health workforce that can be rapidly deployed in the face of a crisis, laboratories that can quickly ramp up testing, and surge capacity that can be called upon to respond.”
For insights into pandemic preparedness initiatives at the Congress in Barcelona this month get your tickets here, and don’t forget to subscribe to our weekly newsletters here!
by Charlotte Kilpatrick | Oct 10, 2024 | Global Health |
The African Union Development Agency – New Partnership for Africa’s Development (AUDA-NEPAD) announced in October 2024 that Wellcome is granting US$12,301,075 to “support the strengthening and harmonisation of regulatory systems and the operationalisation” of the African Medicines Agency (AMA). The grant will help to drive efforts to “overcome regulatory capacity challenges” to improve access to essential medical products and technologies.
The African Medicines Regulatory Harmonisation (AMRH) initiative has been “pivotal” at creating a “cohesive regulatory environment” for the pharmaceutical sector across Africa since 2009. It focuses on using Regional Economic Communities (RECs) to ensure that African populations have access to high-quality, safe, and effective medical products and health technologies. Wellcome’s grant will be used in alignment with AMRH’s vision of “overcoming barriers” like “limited human and institutional capacity, fragmented regulatory processes, and inconsistent technical standards”.
AMA
AMA’s vision is that “African people have access to essential medical products and technologies”; it hopes to achieve this through the mission: “provide leadership in creating an enabling regulatory environment for pharmaceutical sector development in Africa”. The funding is expected to accelerate efforts to create a “unified and efficient” regulatory framework. The partnership between Wellcome and AUDA-NEPAD is a “major advancement in the pursuit of a robust and harmonised regulatory environment” with positive effects for health outcomes in Africa.
Efficient, connected, fair
Symerre Grey-Johnson Director for Human Capital and Institutional Development at AUDA-NEPAD, stated that the “generous support” from Wellcome is a “crucial endorsement of our mission”.
“With the African Medicines Regulatory Harmonisation (AMRH) intiative laying the groundwork for the African Medicines Agency (AMA), this grant will empower us to address significant regulatory challenges and enhance access to essential medical products for millions of Africans.”
Mr Grey-Johnson believes that the collaboration will “solidify the foundation of the AMA” and ensure a “robust and harmonised” regulatory environment across the continent. Dr Sally Nicholas, Wellcome’s Head of Health Systems and Environment, recognised the AMA’s “crucial role” in creating a “more efficient, connected, and fair regulatory system” in Africa.
“Strengthening regulatory systems is fundamental to improving healthcare outcomes for Africa. By supporting innovative partnerships, initiatives, and solutions to help coordinate effectively operationalise the AMA, we can ensure equitable access to much-needed vaccines, treatments, and interventions for those with the greatest need.”
At the Congress in Barcelona this month we look forward to learning about an AMA pilot with MSD in the Supply and Logistics track; get your tickets to join us there and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Oct 10, 2024 | Infection |
In October 2024, the United States CDC reported a third human case of H5 bird flu in the state of California. This announcement followed the identification of two human cases just a week before. All three cases have reported occupational exposure to infected dairy cows, but none has been hospitalised. The CDC risk assessment for the public remains “low”.
Three cases reported
The first two human cases were reported on 3rd October 2024 in people with occupational exposure to infected dairy cows. H5N1 outbreaks in dairy herds were first reported in California in August 2024. The cases had no known link or contact, indicating separate instances of animal-to-human spread. Sequences from these cases confirmed clade 2.3.4.4b A(H5N1) viruses, closely related to viruses detected in dairy cattle. Whole genome sequencing from one of the cases confirmed a B3.13 genotype virus.
“There were no genetic changes observed that are known to be associated with an increased ability to infect or spread between people or known to reduce susceptibility to antiviral medications.”
The third case, reported on 9th October 2024, also reported occupational exposure and no known contact with the other cases. Sequencing of this case is underway. The infected people experienced “mild” symptoms, including conjunctivitis. None of the three cases has been hospitalised.
The broader risk
CDC’s risk assessment for the general public is still “low”. This case takes to total human cases of H5 bird flu to 17 in 2024. Cases have been reported in Texas (1), Michigan (2), Colorado (10), Missouri (1), and California (3). Only one case, in Missouri, has not had source confirmation. The agency emphasises the importance of recommended precautions for people with exposure to infected or potentially infected animals.
At the Congress in Barcelona this month we will explore avian influenza during the One Health and Veterinary track, considering the role of vaccination in One Health strategies and learning from our experts’ experiences. Get your tickets to join us there and don’t forget to subscribe to our weekly newsletters for more health news.
by Charlotte Kilpatrick | Oct 9, 2024 | Global Health |
GSK announced in October 2024 that data from the AreSVI-006 (Adult Respiratory Syncytial Virus) Phase III trial of Arexvy indicate that a single dose could offer protection for three RSV seasons. Arexvy is the world’s first RSV vaccine, first approved by the United States FDA in May 2023 for the prevention of lower respiratory tract disease (LRTD) caused by RSV in older adults. The latest trial evaluates the efficacy of a single dose of the recombinant, adjuvanted vaccine against LRTD caused by RSV in adults aged 60 years and older.
RSV is a “common contagious virus” that affects an estimated 64 million people of all ages globally each year. Adults can be at increased risk for RSV disease due to comorbidities, immune compromised status, or advanced age. RSV causes over 465,000 hospitalisations and 33,000 deaths in adults aged 60 and older in high-income countries.
Clinically meaningful efficacy
The results suggest that after a single dose of the vaccine, cumulative efficacy over three full RSV seasons was clinically meaningful at 62.9% against RSV-LRTD and 67.4% against severe RSV-LRTD compared to placebo. In the third season, vaccine efficacy was 48.0% against RSV-LRTD. The data include efficacy against different RSV subtypes, in adults between 70 and 79 years of age, and those with underlying medical conditions.
“Since RSV can exacerbate medical conditions and potentially lead to hospitalisations, cumulative efficacy over three RSV seasons has the potential for significant health impact.”
Another benefit of this protection is that healthcare professionals might have flexibility to administer the vaccine year-round. Over time, revaccination is “expected to be required to maintain an optimal level of protection”. Therefore, GSK will continue to share efficacy and immune response data to inform decisions on immunisation schedules and future revaccination.
GSK’s Chief Scientific Officer Dr Tony Wood is excited by the data, which show that a single dose could “help protect millions of older adults” to “benefit public health”.
“This is the only RSV vaccine with efficacy and safety data available through three full seasons. We will continue to provide data on longer term follow-up to help recommending bodies determine future revaccination schedules.”
We look forward to hearing from senior representatives of GSK, including for perspectives on directing vaccine development for older populations, at the Congress in Barcelona this month. Get your tickets to join us here, and don’t forget to subscribe to our weekly newsletters here!
by Charlotte Kilpatrick | Oct 9, 2024 | Technology |
In October 2024, CEPI announced that it is awarding funding of up to £3.7 million to support researchers at the University of Sheffield as they seek proof-of-concept for RNAbox. RNAbox is a specialised process designed to scale up the production of mRNA vaccines at regional vaccine sites. It is “easily adaptable and automated”, with the potential to improve global pandemic readiness by enabling increased equitable access to various mRNA vaccines, as and when needed. It also could help speed up responses to future emerging outbreaks.
Addressing mRNA challenges
mRNA vaccines be “more rapidly tailored” to specific diseases or variants, and the technology “holds promise” for different illnesses, including emerging infectious diseases. However, mRNA vaccines are “expensive to manufacture at a high product quality” and require complex cold-chain storage and transportation infrastructure. This makes them “extremely difficult to deliver to remote areas or low-resource settings”.
The RNAbox presents a potential solution to these challenges through its bespoke manufacturing process, designed to overcome the need to deliver the vaccine by facilitating local manufacture at small production sites. The process will run continuously to create between seven and ten times more mRNA at a time and enable more efficient use of raw materials. RNAbox uses digital-twin technology, in which a virtual replica of the vaccine manufacturing process is modelled on a computer in real-time with smart sensors collecting data on the physical product.
CEPI’s interest
CEPI states that the “fast, optimised vaccine production is critical to the 100 Days Mission”. The investment will explore applying the technology to vaccine development for CEPI priority pathogens, including the viruses that cause deadly diseases like Ebola, Lassa fever, MERS, and Nipah. Ingrid Kromann, Acting Executive Director of Manufacturing and Supply Chain at CEPI suggested that the University’s “versatile” technology “builds on the ‘vaccine revolution’ experienced during the COVID-19 pandemic”.
“It aims to overcome a number of scientific hurdles which resulted in poorer countries facing devastating vaccine inequity by helping to make high-quality, low-cost vaccines quickly and easily close to the source of an outbreak.”
Dr Zoltán Kis, School of Chemical, Materials, and Biological Engineering at the University of Sheffield, reflected on the “importance of being prepared” with the “necessary tools”.
“We need to tackle outbreaks equitably around the world, as diseases can spread across country borders.”
The RNAbox will “accelerate the development of new vaccines” and “mass-manufacturing against a wide range of diseases”.
“This transformative technology can also be used to develop much-needed vaccines against a range of unmet needs during non-epidemic/pandemic times. In case of a new epidemic/pandemic, the RNAbox can be quickly adapted to produce vaccines to tackle outbreaks. This will enable vaccine development and manufacturing capacity locally in countries around the world to serve local needs.”
The researchers will work with vaccine manufacturers in low- and middle-income countries to ensure the technology is fit-for-purpose in lower-resource settings.
At the Congress in Barcelona this month we will hear from experts who are revolutionising mRNA vaccine production to ensure products are accessible. Join us there to learn more, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Oct 8, 2024 | Global Health |
A report from Coalition for Life Course Immunisation (CLCI) considers the financial and policy frameworks of various National Immunisation Programmes in Europe with a focus on sustainable financing and informed decision-making. The report addresses access and distribution disparities with “actionable strategies” to ensure everyone receives the vaccinations they need throughout their lives. CLCI describes the analysis as “crucial for stakeholders and policymakers” as a foundation for “advocating for robust, inclusive public health policies” that can be adapting to various healthcare challenges.
Financing and decision-making
The paper presents profiles for 16 European Union Member States: Austria, Belgium, Cyprus, Czechia, Denmark, France, Germany, Greece, Hungary, Italy, Lithuania, Norway, Poland, Romania, Spain, and the Netherlands. These countries are divided into Eastern and Western European nations.
The study finds that the seven Eastern countries had a lower over-65 influenza vaccination coverage rate than the nine Western countries (33% vs 54%). They also spent less of their GDP on healthcare (4.6% vs 6.2%) and less of the healthcare budget on prevention (7.6% vs 10%). Countries with decentralised health systems allocated a higher percentage of their GDP to healthcare and a larger proportion of their healthcare budget to prevention than centralised systems.
7 out of 16 countries reported ringfencing of funds for vaccination and prevention, a common approach for countries that have Ministry of Finance involvement in budgeting. Two countries reported using long-term, multi-year contracts to secure vaccine supply and stabilise financing.
Spotlight on Spain and the Netherlands
As The World Vaccine Congress Europe is taking place in Barcelona this year (2024) and Amsterdam next year (2025) we chose to look more closely at the country profiles of Spain and the Netherlands. The report offers a brief history and an insight into the potential future landscape for both countries:
- Spain – healthcare, including vaccination programmes, has been publicly funded since the establishment of the Spanish National Health System in 1986. Decentralisation in the late 20th century led to “variability” in programme implementation. Spain is “firmly focussed on vaccination as a cost-effective public health measure”. It is increasing investment in public health infrastructure and immunisation coverage will expand to include more diseases and eligible populations. It is also advancing digital transformation through national immunisation registries, enhanced data analytics for decision-making, and digital tools to improve uptake and surveillance.
- The Netherlands – the Dutch National Immunisation Programme (RVP) was established in 1957 to provide free vaccines to all children. This has expanded to include more vaccines. During the COVID-19 pandemic, the budget was allocated “immediately”. Current efforts are underway to “push more proactive allocated budgets to accommodate new vaccines more efficiently”. Demand is driven by an ageing population.
Head-to-head
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Feature
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Spain |
The Netherlands
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Health system
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Decentralised |
Decentralised
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Stakeholders
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The Public Health Commission of the Ministry of Health, the National Immunisation Technical Advisory Group (NITAG), and regional health authorities |
The Health Council, Dutch National Institute for Public Health and the Environment (RIVM), Ministry of Health
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Introducing a new vaccine
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New vaccines are evaluated by NITAG before the Public Health Commission recommends updates to the National Immunisation Plan (NIP) and final financing decisions made by regional Ministries of Finances. This means vaccine recommendations can vary between regions. |
New vaccine recommendations from the European Medicines Agency (EMA) go through the Minister of Health and State Secretary, who asks the Health Council to evaluate before funding is considered. After a recommendation from the Health Council, the MoH asks the RIVM to implement the vaccine in the National Immunisation Plan (NIP).
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Primary funding sources
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Regional governments |
Public funding
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Critical financing challenges
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High cost of new vaccines, decentralised health system, insufficient political will |
No set budget causes delays, economic pressures, and healthcare budget constraints
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% of GDP spent on healthcare
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10.4% |
10.2%
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| % of healthcare budget spent on prevention |
9% |
3.5%
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Calls to action
The report concludes that the landscape of vaccine financing and decision-making in Europe is “complex”, with “significant variations”. Notably, Ministries of Finance play a key role in healthcare budgeting.
“While some countries have implemented sustainability mechanisms, such as long-term contracts and split investments, budget limitations and political will remain significant barriers to expanding adult vaccination programmes.”
Decentralised health systems demonstrated higher healthcare spending and more investment in prevention; however, this did not necessarily correlate with broader adult vaccine coverage.
The report “advocates for an EU-wide integrated approach to enhance the efficacy of national vaccination strategies for adults” with four specific “calls to action”:
- Strengthen political commitment and sustainable financing
- Increase prevention budgets and foster unity
- Enhance understand and support for vaccination
- Promote comprehensive immunisation programmes
Is your country profile presented in the report? Do you find any of the results surprising, and do you agree with the calls to action? At the Congress in Barcelona this month we look forward to discussing different financing and decision-making approaches with global health experts. Get your tickets to join us for these conversations, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Oct 8, 2024 | Infection |
A recent WHO situation report on the mpox PHEIC reveals that 14 countries on the continent have reported mpox cases in the last six weeks and are considered to have “active” outbreaks. The most affected country in 2024 is still the Democratic Republic of the Congo (DRC), which recently announced the start of an mpox vaccination campaign. The update presents reported confirmed mpox cases and deaths as well as reported suspected mpox cases, as defined by the countries that have reported them.
Risk levels
The report presents the mpox risk of geographical spread and potential impact on health in various regions:
- Eastern Democratic Republic of the Congo and neighbouring countries: high
- Areas of the Democratic Republic of the Congo where mpox is endemic: high
- Nigeria and other areas of West, Central, and East Africa where mpox is endemic: moderate
- All other countries in Africa and around the world: moderate
However, the report notes that individual country or regional bloc assessments may vary, and the risk could be assessed as low. Individual-level risk is “largely dependent on individual factors” like exposure risk and immune status.
Cases
By 29th September, 14 countries on the continent have reported mpox cases in the last six weeks. The most affected country in 2024 is the Democratic Republic of the Congo (DRC) with 5,610 confirmed cases and 25 deaths, followed by Burundi, with 853 confirmed cases and no deaths, and Nigeria, with 78 confirmed cases and no deaths. Although the epidemic curve of confirmed cases by country suggests a decline in reported cases in DRC, this trend “should be interpreted with caution” amid “reports of limited testing and stockout of testing supplies”.
Focus on North Kivu
As of 28th September 2024, the province of North Kivu in DRC had reported 323 confirmed mpox cases, including two confirmed deaths. After initial detection in May 2024 genomic sequencing analysis revealed clade Ib monkeypox virus (MPXV). There are 34 health zones in North Kivu; 14 have reported confirmed mpox cases, The most affected zones are Goma, Karisimbi, and Nyiragongo. 1,108 suspected mpox cases in North Kivu have been tested with a test positivity of 29%. The number of confirmed cases in the province continues to increase.
Among confirmed cases, 117 (36%) are individuals living in camps for Internally Displaced People (IDP), in the three most affected health zones. 13 IDP camps have reported at least one mpox case; the most affected are Munigi, Mugunga, Rusayo, and Kanyaruchinya. 8 out of 14 IDP camps (57%) have reported only one case, which indicates sporadic introduction, likely from outside the camp. Transmission may be sustained in the other six, which show more cases over time.
In North Kivu, around 50% of confirmed mpox cases are among adults and 54% of total cases are male. However, in IDP camps, approximately 75% of mpox cases are among children up to 17 years old and are evenly distributed between males and females. WHO believes that mpox transmission in North Kivu is “exclusively” human-to-human, mainly at the community level. 117 out of 323 (36%) cases have a known epidemiological link. The mode of transmission for 109 cases (34%) is reported to be sexual contact; among these cases, 57 (52%) are reported among female sex workers.
216 out of 323 (67%) cases have recovered from the disease; 109 are in isolation, 33 in the household, and 76 in healthcare facilities. 19 (9%) cases have presented complications and two have died in hospital.
Clade Ib detected in India
On 1st October 2024, the Ministry of Health and Family Welfare of India notified WHO of the first mpox case due to MPXV clade Ib. The National Focal Point reports that the case is an adult male, Indian national, with a recent history of international travel to the United Arab Emirates (UAE). The patient developed mpox symptoms on 8th September in UAE before arriving in India on 13th September. On 16th September he was admitted to a public hospital.
On 19th September, samples were tested at the National Institute of Virology (NIV) in Pune, confirming MPXV infection. The patient recovered without complications and was discharged on 30th September 2024. The health authorities in UAE are conducting a detailed case and contacts investigation to finalise the “comprehensive verification and validation process as per IHR procedures”.
This is the second reported case of this clade MPXV infection in the WHO South-East Asia Region (SEAR) and the third reported case of clade Ib MPXV infection outside the African Region. However, the first clade Ib infection in SEAR, reported in Thailand, and the clade Ib infection in Sweden, had a recent history of travel to affected countries in Africa, which this case did not.
Vaccine updates
WHO indicates that it is finalising the issuance of prequalification age extension of MVA-BN for persons 12-17 years old after European Medicines Agency (EMA) authorisation. It is providing “strategic and technical support” to the African Vaccine Regulatory Forum (AVAREF) and issuance of emergency use authorisation for MVA-BN to national regulatory authorities. In collaboration with AFRO, DRC, Ghana, Nigeria, Rwanda, and Tanzania, WHO is harmonising the cohort safety event monitoring protocol following mpox vaccination and ensuring global data collection.
With receipt of 265,000 doses of MVA-BN, DRC has begun a vaccination campaign in North Kivu with the intention of expanding to 11 of the most affected health zones across various provinces.
Join us at the Congress in Washington in April next year to reflect on the global response to this outbreak and hear updates on continued mpox vaccine development, and don’t forget to subscribe to our weekly newsletters for more insights.
by Charlotte Kilpatrick | Oct 8, 2024 | Therapeutic |
A study in the Journal for ImmunoTherapy of Cancer finds that vaccination in a clinically relevant genetic cancer mouse model generated a population of functional progenitor tumour-specific CD8 T cells (TST) and halted cancer progression, in contrast to immune checkpoint blockade (IBT) therapies. The authors hope that immunisation could be the “most effective strategy” for patients with early cancers or at high risk of cancer recurrence. This study takes a different approach to many cancer vaccine studies, which tend to focus on patients with advanced tumours.
Cancer vaccine potential
The authors recognise the transformational role of immunotherapies in the cancer treatment landscape, particularly in the case of immune checkpoint blockade (ICB). However, vaccines for non-viral cancers have had “more limited success”. Many studies on tumour-specific CD8 T cell (TST) vaccine responses are conducted in the established/late tumour setting, so less is known about how TST “respond and differentiate” in response to immunotherapy during early stages of tumorigenesis.
Previously, the authors developed an autochthonous mouse model of liver cancer (AST;Cre-ERT2) to initiate liver carcinogenesis with tamoxifen (TAM)-induced Cre-mediated SV40 large T antigen (TAG) expression in hepatocytes. TAG functions as an oncogene and a tumour-specific neoantigen recognised by CD8 T cells, so the model enables “precise temporal control” of the duration of TST interactions with transformed hepatocytes and tumours. In contrast to human tumours, which “arise sporadically and progress clonally”, TAM-induced oncogene induction is “highly efficient”, resulting in high antigen burden even at early stages.
The study
The researchers allowed AST;Cre-ERT2 mice to undergo stochastic TAG oncogene activation through sporadic, TAM-independent Cre-mediated activity. To explore TST responses against TAG-driven tumours they used congenic donor lymphocytes from transgenic mice, in which CD8 T cells express a single T cell receptor (TCR) specific for TAG epitope-I (TCRTAG). They found that TST became dysfunctional in TAM-treated AST;Cre-ERT2 mice and were “unable to halt tumour progression”. TAM-treated AST;Cre-ERT2 mice had a “substantial” tumour antigen burden, even at early stages of tumorigenesis.
To compare initial TST differentiation in mice with early liver lesions against those with late liver lesions, the researchers transferred CFSE-labelled naïve TCRTAG into early and late time point AST;Cre-ERT2 mice. TCRTAG in mice with early lesions divided at a slower rate, particularly in the spleen and ldLN, and there were fewer TCRTAG in the spleens, ldLN, and livers of early mice. Decreased TST proliferation in mice with early lesions could be due to the lower TAG antigen burden. Although nearly all TCRTAG in mice with late lesions and most in mice with early lesions failed to produce effector cytokines TNFα and IFNγ within 60 hours of transfer, a population of TCRTAG in were identified in the spleen and liver of mice with early lesions. These could produce effector cytokines TNFα and IFNγ.
“Thus, in hosts with sporadic early lesions, a subset of TST resisted rapid differentiation to the dysfunctional state, raising the possibility that this subset might be amenable to immunotherapeutic reprogramming/rescue.”
To see if this functional TST subset persisted, the authors examined TCRTAG immunophenotype and function 5 days and 21 days post-transfer into early or late AST;Cre-ERT2 mice. While fewer TCRTAG were found in mice with early lesions compared to late lesions at 5 days, the difference became less pronounced at 21 days. In both groups TCRTAG upregulated CD44, which indicates antigen exposure and activation. TCRTAG in early mice continued to express higher levels of PD1 than naïve TCRTAG, suggesting that PD1 expression can identify tumour-reactive TST in hosts with early lesions.
The next consideration was if the functional TST subset in mice with early lesions could be harnessed to stop tumour progression. LM, a gram-positive intracellular bacterium, induces strong CD4 and CD8 T cell responses. The researchers used an actA inIB deficient attenuated LM vaccination strain to test if early vaccination of AST;Cre-ERT2 would protect mice against liver cancer progression. Mice were either left untreated, given a single dose of empty LM, or vaccinated with a single dose of LM- TAG.
“LM- TAG–immunisation conferred a major survival advantage, with all mice remaining tumour-free and one mouse euthanised for dermatitis without any evidence of liver tumours.”
The mice in untreated and empty LM groups reached endpoint with “multiple” large liver tumours and increased liver weight. At endpoint, most TCRTAG in the LM- TAG–immunised made effector cytokines, in contrast to the TCRTAG in tumour-bearing mice in the other groups, which were “largely unable to produce effector cytokines”.
Vaccination vs ICB
“An important and open question in cancer immunotherapy is how ICB versus vaccination compares in boosting anticancer immune responses, and how best to combine and sequence these therapies.”
A comparison of ICB, LMTAG vaccination, and combined ICB/LMTAG vaccination found that ICB conferred no benefit in comparison with isotype control antibodies (iso). By contrast, LMTAG and ICB/LMTAG treated mice had no evidence of tumour progression at 400+ days. Furthermore, LMTAG vaccination, whether alone or in combination, led to a “substantial increase” in TST numbers and IFNγ production, while ICB alone had “little impact”.
LM-based vaccines have had “poor or mixed results” in clinical trials, often with a target of patients with advanced or refractory cancers. The authors hope that their studies offer “mechanistic insight” as to why these fail in patients with advanced cancers: “for vaccines to be effective, a progenitor TST population must be present”. Although the apparent superiority of vaccination over ICB “may be surprising at first glance”, the authors highlight an important point, that “not all TCF1+TST are functional, nor does ICB alone lead to functional TST”. However, the findings suggest that LMTAG vaccination maintains or rescues functional progenitor TCF1+TST.
Timing is important
Dr Mary Philip, associate director of the Vanderbilt Institute for Infection, Immunology, and Inflammation, commented that the study “suggests that the timing of vaccination is important”.
“A unique feature of our study is that these mice are at high, essentially 100% risk of developing cancers, so the fact that a single immunisation at the right time can give lifelong protection is pretty striking.”
Dr Philip reflected that very few studies follow mice “so long after vaccination” and find them tumour free for two years.
“ICB works by taking the brakes off T cells, but if the T cells have never been properly activated, they are like cars without gas, and ICB doesn’t work. The vaccination boosts the T cells into a functional state so that they can eliminate early cancer cells.”
For more progress updates from cancer vaccine researchers at the Congress in Barcelona this month, get your tickets to join us here. Don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Oct 7, 2024 | Global Health |
Gavi shared the 2023 Annual Progress Report in October 2024, highlighting that more than 1.3 million future deaths were averted in 2023 through Gavi-supported vaccination programmes. The report details progress on strategic goals and reveals that the number of children protected with routine childhood vaccines since 2000 has exceeded 1.1 billion. These milestones also have economic benefits for Gavi-supported countries; the report suggests that this totals US$ 52 billion since 2021.
Chair of the Gavi Board, José Manuel Barroso, emphasised the importance of vaccinating children and vulnerable populations.
“We not only enable millions of people to lead healthier, more fulfilled lives [but we also] contribute to families’ prosperity, to strong and more stable communities, and to economic development that is already translating into countries’ paying more towards their immunisation programmes than ever before.”
Dr Sania Nishtar, Gavi’s CEO, commented that many Gavi countries are “on the front line of climate change, with many vulnerable to economic instability and geopolitical tension”.
“For them to be able to immunise more children, not to mention expand important programmes such as HPV, deserves recognition. Fully funding Gavi for its next five-year period will be crucial in expanding these hard-won gains and helping countries further along the pathway to fully sustaining their own immunisation programmes.”
Indicators and goals
Gavi partners and countries are “on track” to achieve most of the six mission indicators of the 2021-2025 strategic period:
- Under-five mortality rate
- Future deaths averted with Gavi support
- Future DALYs averted
- Reduction in number of zero-dose children
- Unique children immunised through routine immunisation with Gavi support
- Economic benefits generated through Gavi-supported immunisations
The mission is supported by four strategic goals
- Introduce and scale up vaccines
- Strengthen health systems to increase equity in immunisation
- Improve sustainability of immunisation programmes
- Ensure healthy markets for vaccines and related products
Vaccines
National Immunisation Coverage estimates in July 2024 confirmed that Gavi is on track in reaching children with new vaccines but must increase efforts to reach zero-dose and under-immunised children. At the end of 2023, Gavi had helped countries reach more than 1.1 billion children with routine immunisations since 2000. This means that the Investment Opportunity 2021-2025 commitment was achieved two years early. Gavi-supported countries completed a total of 13 routine introductions, taking the total introductions from 2021-2023 to 42.
Coverage of the third dose of diphtheria, tetanus, and pertussis-containing vaccine (DTP3) in 57 lower-income Gavi-supported countries remained “stable” at 80%. Apart from the pentavalent vaccine, Gavi-supported vaccines had higher coverage in 2023 than before the pandemic in 2019. After the opening of the support window for the second dose of inactivated polio vaccine (IPV2) in 2021, overall coverage in Gavi-supported countries increased rapidly to 27% by the end of 2023. The revitalisation of the HPV vaccine programme had “significant” effects: countries fully immunised more than 14 million girls with Gavi support in 2023.
Gavi’s vaccine portfolio has “grown significantly” over time; Gavi now supports vaccines against 20 infectious diseases through 53 product presentations.
Strategy indicators
Breadth of protection: In 2023 the 57 Gavi-supported countries (Gavi57) increased breadth of protection by 3 percentage points to 56%, against an implied target of 60% by 2025.
Coverage: Across the four vaccines included in the Sustainable Development Goal (SDG) indicator 3.b.1, the third dose of pneumococcal conjugate vaccine (PCV3) and the last dose in the schedule of human papillomavirus vaccine (HPVC) were trending higher in 2023 than originally projected. However, coverage of the second dose of measles-containing vaccine (MCV2) was “slightly behind but improving” and coverage of the third dose of DTP3 is “off track”.
Rate of scale up of new vaccines: Coverage of three vaccines (yellow fever: 97%, PCV: 93%, and rotaC: 93%) exceeded the benchmark. RotaC recovered from 2022 supply disruptions. Coverage of MCV2 remained under the 90% relative coverage target.
Introductions: 13 new routine introductions took place in 2023 against a milestone of 21. The cumulative total for introductions in 2021-2023 is 42, just “moderately delayed” against the target of 82 by 2025.
Country prioritisation: Gavi Secretariat considered if funding applications presented the three criteria (disease burden, effectiveness of vaccination, accounting for budget to meet requirements for vaccine procurement and sustain immunisation levels after transition from Gavi support). 93% of applications considered disease burden and increase in budget needed; 76% considered effectiveness of vaccination. 41 applications were reviewed from 2021 to 2023, increasing as countries submitted malaria vaccine applications.
Measles: 75% of children aged under five who were previously unvaccinated against measles received an MCV dose among countries conducting a Gavi-supported preventing MCV campaign.
Timely detection and response: Detection and response challenges, including “suboptimal surveillance” and lack of “robust” preparedness plans and locally available resources “persisted” in 2023. However, 5 out of 28 Gavi-supported outbreak responses with timeliness data met the disease-specific timeliness threshold in 2023. Measles-containing and yellow fever vaccines achieved higher rates of timely response than cholera, Ebola, and meningitis vaccines.
The future
Commenting on the progress presented in the report, UNICEF Executive Director Catherine Russell affirmed that “no child should die from vaccine-preventable diseases”.
“Through Gavi, the Vaccine Alliance we continue to bridge the gap between life-saving vaccines and the children who need them.”
To achieve the goals of the next strategic period, 2026-2030, Gavi needs to meet the funding target of US$9 billion. This will enable the organisation to expand protection against more diseases, ensure that the most vulnerable populations are “not left behind”, and protect the world against disease outbreaks. WHO Director-General Dr Tedros Adhanom Ghebreyesus stated that “vaccines are among the most powerful inventions in history”.
“With continued and increased investment in Gavi, we can harness their power, saving millions of lives in the coming decades.”
How do you think Gavi can continue to make immunisation progress into its next strategic period? What are the key challenges it faces? For more on the biggest vaccine challenges and opportunities to overcome them, join us at the Congress in Barcelona this month or subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Oct 7, 2024 | Technology |
In October 2024, WHO announced that a fourth WHO-prequalified human papillomavirus (HPV) vaccine product, Cecolin, has been confirmed for use in a single-dose schedule. This update is an “important milestone” that will contribute to “improving sustainable supply of HPV vaccines”, ensuring that more people get access to the vaccines that prevent cervical cancer. HPV vaccine programmes have been “hampered” by supply shortages since 2018, and recent production challenges have led to further shortfalls, which will affect girls in need of HPV vaccines Africa and Asia.
Eliminating cervical cancer by tackling HPV
More than 95% of the 660,000 annual cervical cases are caused by HPV. Every two minutes, a woman dies from the disease, and 90% of these deaths happen in low- and middle-income countries. 19 out of the 20 “hardest hit” countries are in Africa. However, vaccination is an effective way of addressing this health need. Dr Tedros Adhanom Ghebreyesus, WHO Director-General, states that “we have the ability to eliminate cervical cancer, along with its painful inequities”.
“By adding another option for a one-dose HPV vaccination schedule, we have taken another step closer in consigning cervical cancer to history.”
Dr Kate O’Brien, Director of the Department of Immunisation, Vaccines, and Biologicals at WHO, reflected that achieving a 90% coverage in girls by the age of 15 is the target of the first pillar of WHO’s global strategy for cervical cancer elimination.
“Given the continuing supply challenges, this addition of single dose vaccine product means countries will have greater choice of vaccines to reach more girls.”
Cecolin
Cecolin is a bivalent HPV vaccine delivered intramuscularly as a single dose. It is manufactured by Xiamen Innovax Biotech and should be stored between 2°C and 8°C. It is designed to protect against HPV types 16 and 18, which are commonly associated with the development of cancer. When Cecolin received prequalification, PATH stated that it had provided “technical assistance” for the process to facilitate greater accessibility. PATH’s China country representative Yuan Yuan commented that the vaccine would put the world “on its way to more equitable HPV vaccination”.
Single-dose coverage
Several products that were initially prequalified for use in a 2-dose schedule can now be used in a single-dose schedule. Cecolin can be recommended for “off-label” use after data support the modified schedule until the manufacturer adds the modified use to the label. Data from July 2024 show an increase in one dose HPV vaccine coverage among girls aged 9-14 years, from 20% in 2022 to 27% in 2023. In 2023, 37 countries were implementing a single-dose schedule; this increased to 57 by September 2024. WHO suggests that the adoption of a single-dose schedule has resulted in “at least” 6 million additional girls being reached with HPV vaccines in 2023.
For insights into the role of vaccination in elimination strategies, why not join us at the Congress in Barcelona this month? Don’t forget to subscribe to our weekly newsletters here for more vaccine news.
by Charlotte Kilpatrick | Oct 7, 2024 | Global Health |
WHO Africa reported in October 2024 that the Democratic Republic of the Congo (DRC) has started a vaccination campaign as part of outbreak control efforts against mpox. The vaccination drive has launched in the eastern North Kivu province and will prioritise health workers and frontline responders, contacts of confirmed cases, contacts of those contacts, and other at-risk groups. It will later be implemented in 11 of the most affected health zones in Equateur, North Kivu, Sankiri, South Kivu, Sud-Ubangi, and Tshopo provinces.
Addressing the emergency
The Democratic Republic of the Congo (DRC) has reported more than 30,000 suspected and laboratory-confirmed cases and 990 deaths since the start of 2024. These numbers account for 90% of the cases reported from 15 countries in the African region this year. WHO recommends that vaccination should form part of a “comprehensive response” involving enhanced surveillance, community engagement, and case management. It is working with partners and the national authorities to “scale up and reinforce all the key control measures”.
In preparation for the mpox vaccination campaign, WHO has supported national health authorities in training health workers, enhancing vaccine delivery systems and infrastructure, and community engagement. There are also efforts to “reinforce measures to identify and address” vaccine misinformation and disinformation, responding with increased access to accurate information.
Delivering doses to affected areas
Noting that mpox vaccines are “currently in short supply, especially in Africa”, WHO is encouraging global collaboration to get doses to the people who need them most. In September, WHO prequalified MVA-BN for mpox, which is “expected to facilitate timely and increased access”. It is also working with partners like Gavi and UNICEF to establish a distribution mechanism for donated doses and direct procurements. DRC has received 265,000 doses of MVA-BN, donated by the European Commission’s Health Emergency Preparedness and Response Authority, Gavi, and the United States Government.
WHO Regional Director for Africa, Dr Matshidiso Moeti, expressed gratitude to these partners for their donations.
“As we rally efforts to stop the mpox outbreak, the rollout of the vaccine marks an important step in limiting the spread of the virus and ensuring the safety of families and communities.”
Dr Moeti commented that WHO is “working closely with the national authorities to effectively deliver the vaccines to those who need them most”. Africa CDC also recognised the collaborative effort, which “underscores the collective global commitment” to controlling the outbreak in Africa. H.E. Dr Jean Kaseya, Africa CDC Director General, commended the DRC’s “swift action” in launching the campaign, which “showcases the strength of its public health leadership”.
“By prioritising vulnerable populations, including frontline health workers and those most at risk, the country is taking critical steps to contain the outbreak. Africa CDC remains committed to working closely with the DRC to ensure vaccines reach those who need them the most, while also working to strengthen health systems to prevent future outbreaks. Our top priority is to secure safe and effective vaccines for children in the next phase of vaccination.”
Mpox vaccination will be a key area of high-level discussions at the Congress in Washington next April, including on a keynote panel that will consider the “role of vaccines in a changing world”. Get your tickets to join us for these conversations, and don’t forget to subscribe to weekly vaccine updates 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 3, 2024 | Global Health |
WHO announced in October 2024 that it is launching the Global Strategic Preparedness, Readiness, and Response Plan (SPRP) to tackle dengue and other Aedes-borne arboviruses. The Plan is intended to reduce the burden of disease, suffering, and deaths from dengue and other Aedes-borne arboviral diseases, like Zika and chikungunya, by “fostering a global coordinated response”. It presents priority actions to control transmission and offers recommendations to affected countries across various sectors. With five “key components”, the Plan is to be implemented over one year until September 2025, demanding US$ 55 million.
“The SPRP is a call to action for all stakeholders – from government agencies and health-care providers to communities and individuals – to join forces in the fight against dengue and other Aedes-borne arboviruses, through innovation, new technologies, and improved vector control strategies.”
Turning the tide
In the foreword by WHO Director-General Dr Tedros Adhanom Ghebreyesus we learn that dengue has “afflicted humanity for centuries, and possibly longer”; the first report of a clinically compatible case is recorded in a Chinese medical encyclopaedia in 992. From a much more contemporary perspective, dengue has spread “rapidly” in the past 20 years, enabled by “increased global travel and the effects of climate change”. Between 2000 and 2019, WHO documented a “tenfold surge” in reported cases, to 5.2 million. Since then, the surge has continued; over 12.3 million cases were reported by the end of August 2024.
The global prevalence and effects of arboviruses like dengue are a “significant threat to public health”, particularly in tropical areas where they are endemic. Addressing this threat demands a “concerted, strategic, and informed response”, which the Director-General hopes to achieve with the SPRP, a “comprehensive plan” to outline ways of controlling Aedes-borne arbovirus transmission in affected countries.
“Our multifaceted approach emphasises integrated surveillance, laboratory diagnosis, vector control, community engagement, clinical management, and research and development.”
This approach should reduce the burden of disease, save lives, and minimise the socioeconomic consequences of these diseases. Furthermore, the Plan includes measures for “safe programming” to ensure interventions are “secure and do not exacerbate the risk” for those who are already vulnerable to disease or those involved in responding to the crisis. Dr Tedros states that prevention and control is a “shared responsibility”.
“Together, we can turn the tide against this disease, protect vulnerable populations, and pave the way for a healthier future.”
Understanding the threat
Dengue is a challenge across all of WHO’s regions, endemic in more than 100 countries. Various factors, such as unplanned urbanisation and the effects of climate change, fuel the spread of dengue and other Aedes-borne arboviruses, such as Zika and chikungunya, putting more than four billion people at risk. The growing threat must be addressed with a “robust and dynamic strategy” that accounts for the current global epidemiological landscape. This is complicated by the “still developing” global surveillance system.
Transmission drivers like the effects of climate change and population growth can explain the increase of these infections in some areas, but they also point to the need for a multisectoral approach to prevent and respond to outbreaks.
The Plan
The Plan is intended to “reduce the burden of disease and deaths from dengue and other Aedes-borne arbovirus diseases in all affected WHO regions”. The strategic objective is “to accelerate progress in preventing and controlling dengue and other Aedes-borne arboviral disease outbreaks worldwide”, with the following specific objectives:
- Strengthen global multisectoral coordination and collaboration among stakeholders and partners in preparedness, response, and resilience to dengue and other Aedes-borne arbovirus diseases
- Enhance the capacity of Member States in early detection, reporting, confirmation, and response to outbreaks of dengue and other Aedes-borne arboviruses
- Strengthen the capacity of Member States to implement effective vaccination and integrated vector management strategies for mitigating the transmission of dengue and other Aedes-borne arboviruses
The SPRP combines strategic interventions tailored to local contexts and leverages inter-stakeholder synergies to “confront the challenges” posed by these diseases and move closer to controlling them. The following “interconnected pillars” are included in the multidisciplinary approach:
- Leadership, coordination, planning, monitoring, and prevention of sexual misconduct
- Risk communication and community engagement (RCCE) and infodemic management
- Surveillance, case investigation, and contact tracing
- Travel, trade, and points of entry surveillance and control
- Laboratory and diagnostics
- Integrated vector management and WASH & IPC
- Clinical management and therapeutics
- Operational support and logistics
- Essential health services and systems
- Vaccination
- Research, innovation, and evidence
The 5Cs
The SPRP aligns with WHO’s 2023 Framework for Health Emergency Prevention, Preparedness, Response, and Resilience (HEPR) with a focus on five “core health emergency components”:
- Collaborative surveillance
- Strong national integrated disease, threat, and vulnerability surveillance,
- Effective diagnostics and laboratory capacity for pathogen and genomic surveillance
- Collaborative approaches for event detection, risk assessment, and response monitoring
- Community protection
- Community engagement, risk communication, and infodemic management
- Population and environmental public health interventions
- Multisectoral action for social and economic protection
- Access to countermeasures
- Fast tracked research and development
- Scalable manufacturing platforms
- Coordinated supply chains and emergency
- Emergency coordination
- Strengthened workforce capacity for health emergencies
- Strengthening health emergency preparedness, readiness, and resilience
- Health emergency alert and response coordination
- Safe and scalable care
- Scalable clinical care during emergencies
- Protection of health workers and patients
- Maintenance of essential health services
How do you think the SPRP can be effectively translated into specific contexts and implemented sustainably?
For insights into vaccination efforts for diseases that are being exacerbated by the effects of climate change, get your tickets to the Congress in Barcelona this month, or subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Oct 3, 2024 | Infection |
Since this article was published, Politico has reported that the previously suspected cases in Hamburg tested negative for Marburg virus with a PCR test and will be monitored throughout the incubation period of up to 21 days.
“There was no danger to fellow passengers on the train or in the plane at any time.”
(more…)
by Charlotte Kilpatrick | Oct 3, 2024 | Technology |
In October 2024, SK bioscience announced the successful completion of its acquisition of a controlling stake in IDT Biologika. This follows the announcement in June 2024 that SK bioscience intended to acquire 60% of IDT Biologika’s shares from the Klocke Group to “leap forward into global markets”. Since the signing of the sale and purchase agreement, SK bioscience has finalised the acquisition after obtaining the necessary approvals. The companies have established a plan for a post-merger integration (PMI) process of around 100 days. This will improve both companies’ “management effectiveness” and “encourage systematic integration for business growth”.
Building foundations
During the PMI, the companies will “build a foundation” for the growth of IDT Biologika through a series of projects. The first element seeks to maximise the utilisation rate of IDT Biologika’s manufacturing facilities and new capacities for drug substance (DS) and drug product (DP) for major projects with global pharmaceutical companies. SK bioscience also hopes to create a framework to expand existing contracts and win further projects for clinical trials and late-stage cell and gene therapy (CGT) projects. Alongside this, the portfolio of available cell lines will be expanded to address new customers, and the development of recombinant vaccines will be advanced.
SK biosciences will invest in high-growth businesses such as pre-filled syringes (PFS), recombinant vaccines, and CGT. This encompasses oncolytic virus (OV), adeno-associated virus (AAV), and lentivirus (LV). The company will also transfer technology and production to IDT Biologika for main products such as flu, shingles, chickenpox, and typhoid vaccines.
To “ensure synergies”, executives from both the Klocke Group and SK bioscience will serve on IDT Biologika’s Advisory Board. The Board will ensure “independent management while carrying out cultural integration”. Dr Ulrich Valley, CEO of IDT Biologika, is “convinced” that the milestone will “contribute to future growth and to our vision of a leading CDMO”.
“This global strategic cooperation is an important driver for our innovative strength, competitiveness, and sustainable success, built on a foundation of trust and common goals.”
Dr Valley is “certain” that Sk bioscience and IDT Biologika can “achieve great things together by combining our competences and capabilities”. President and CEO of SK bioscience, Jaeyong Ahn, commented that the with the successful completion of the acquisition, the two companies “now unite one family”.
“The capabilities and technologies of the two companies are expected to generate significant synergies, and we will accelerate our global expansion.”
We look forward to hearing from IDT Biologika on how to successfully scaling up for vaccine and CGT manufacturing at the Congress in Barcelona this month. Get your tickets to join us there, and don’t forget to subscribe to our newsletters for the latest vaccine news.
