MenFive Phase 3 study results demonstrate strong safety and immunogenicity

Results from a pivotal Phase 3 clinical study of Serum Institute of India Pvt. Ltd.’s (SIIPL’s) MenFive® vaccine (previously known as NmCV-5) were recently published in the New England Journal of Medicine. The vaccine, which protects against meningococcal meningitis serogroups A, C, W, Y, and X, was found to be safe, well tolerated, and capable of producing a strong immune response to all five serogroups. Developed over a decade-plus period by SIIPL and PATH, with funding from the United Kingdom’s Foreign, Commonwealth & Development Office, MenFive is designed to eliminate annual meningococcal meningitis outbreaks and epidemics in the African meningitis belt. Moreover, it is the only vaccine that prevents meningitis caused by serogroup X, a pathogen increasingly implicated in African meningitis outbreaks.

MenFive builds on the legacy of MenAfriVac®, SIIPL’s groundbreaking vaccine—developed in partnership with PATH and the World Health Organization (WHO)—that eliminated meningitis A outbreaks from the African meningitis belt following its 2010 introduction. MenFive received WHO prequalification in July 2023 and is approved for use in individuals 1 to 85 years of age. MenFive will initially be used in reactive campaigns for meningitis outbreaks. Discussions are underway about ways to incorporate MenFive into mass vaccination campaigns and/or routine immunization.

Seasonal malaria vaccine-drug combination dramatically reduces cases and deaths

Final results of a study published in The Lancet Infectious Diseases confirm that the benefits of combining the RTS,S/AS01E (RTS,S) malaria vaccine with antimalarial drugs in settings of highly seasonal malaria transmission continue over five years (three-year results were published in 2021). The vaccine-drug combination reduced cases of severe malaria and deaths from malaria in young children by nearly two-thirds and clinical malaria episodes by nearly 60 percent, compared with either RTS,S vaccination or seasonal malaria chemoprevention (SMC) alone. The study also confirmed that RTS,S was “non-inferior” to SMC in preventing malaria in highly seasonal settings.

These results come from a two-year extension of the Phase 3 study begun in Burkina Faso and Mali in 2017 that followed more than 5,000 children aged 5 to 17 months at first vaccination. The study was coordinated by the London School of Hygiene & Tropical Medicine with partners Institut des Sciences et Techniques and Institut de Recherche en Sciences de la Santé, Burkina Faso; the Malaria Research and Training Center, University of Sciences, Techniques and Technologies of Bamako, Mali; and PATH. The trial was funded by the United Kingdom’s Joint Global Health Trials and PATH, and the RTS,S vaccine was donated by GSK.

Study of Africa’s vaccine manufacturing capacity offers insights for long-term success

Together, the Africa Centres for Disease Control and Prevention (Africa CDC), the Clinton Health Access Initiative (CHAI), and PATH assessed the current and planned vaccine manufacturing capacity in Africa to generate insights into what is needed to develop a robust and sustainable vaccine manufacturing ecosystem. African vaccine manufacturing is set to expand dramatically as the continent works to safeguard itself against future pandemics and disease outbreaks. A clear picture of gaps and needs ensures alignment of all stakeholders and more strategic investments.

Research shows that African vaccine manufacturing capacity is heavily concentrated on form/fill/finish with a significant level of additional capacity still planned. Conversely, capacity to produce antigens locally is very limited, even when capacity expansion plans are taken into consideration. Additionally, there is a strong reliance on non-African vaccine manufacturers for technology transfers, but much of the current and planned manufacturing capacity does not have technology transfers in place. The study, summarized in a new briefing paper, also found that while many vaccine manufacturers have access to financing, further developing their commercial capabilities will improve the odds of success for new facilities. This information can help stakeholders, governments, and funders better coordinate and prioritize development efforts, interventions, and investments.

Interview

Q&A with Deborah Higgin

PATH applauds news of the first respiratory syncytial virus (RSV) maternal vaccine’licensure in the US and Europe. Deborah Higgins, director of PATH’s RSV vaccine project, discusses why this milestone matters for infant health.

Q: Why is protecting infants from RSV important?
A: RSV is the world’s top cause of severe respiratory infections and hospitalizations in young children. Though any child can get severely ill or hospitalized due to RSV, infants are the most vulnerable. In fact, RSV causes 1 in every 28 deaths before six months of age. Serious complications, including bronchiolitis and pneumonia, can harm long-term lung health.

Q: Why maternal immunization?
A: Vaccination in pregnancy is a key strategy for infant RSV disease prevention. It can enhance a pregnant individual’s immunity and increase antibody transfer to baby across the placenta for protection from birth and for months thereafter.

Q: What’s next?
A: The new RSV maternal vaccine, developed by Pfizer, Inc., is a long-awaited milestone for infant respiratory health. A crucial next step is to accelerate the timeline to WHO prequalification and access for low- and middle-income markets, where over 98 percent of RSV deaths occur. We must raise awareness now and communications resources curated by PATH and WHO can help.

CLINICAL UPDATES

August 2023

• A controlled human infection model challenge/rechallenge trial (NCT04992520) to study two Shigella challenge strains (S. sonnei strain 53G and S. flexneri 2a strain 2457T) completed its last subject, last visit. The study was conducted in Baltimore, Maryland, enrolled 46 adults, and aimed to determine if challenging volunteers with one species of Shigella induces cross-protective immunity when a subset of volunteers is challenged later with the second strain. Preliminary results will be available in May 2024.

September 2023

• An open-label Phase 1/2a trial (NCT05978037) evaluating the safety, immunogenicity, and efficacy of the RH5.2-virus-like particle (VLP) malaria vaccine candidate was initiated in Oxford, United Kingdom. Up to 56 healthy adults will be enrolled in the trial, which will assess different formulations and regimens of RH5.2-VLP in Matrix-MTM adjuvant. This clinical study is supported by the US Agency for International Development (USAID) Malaria Vaccine Development Program under the Innovations in Malaria Vaccine Development contract.

• A Phase 3 trial (NCT04010448) evaluating the safety, immunogenicity, and efficacy of an injectable, non-replicating rotavirus vaccine (NRRV) candidate completed its last subject, last visit at all study sites in Ghana, Malawi, and Zambia. The trial was closed early due to insufficient evidence at the interim analysis that the NRRV candidate provides superior protection compared to a licensed oral rotavirus comparator vaccine. A follow-on, observational study to assess the incidence of moderate-to-severe rotavirus gastroenteritis during the second year of life in Phase 3 study participants from Ghana and Malawi was initiated.

Resources and opportunities

New and updated resources

Advancing novel oral polio vaccines: Planning for long-term protection against polio resurgence fact sheet

In Senegal and beyond, Cathy Ndiaye advocates for healthy communities web article

COVID-19 Maternal Immunization Resource Library

Current and planned vaccine manufacturing in Africa briefing paper

On the verge of RSV disease prevention toolkit

Presentations on single-dose HPV vaccination slide decks

Untangling the complexity of HPV vaccination costs web article

Vaccine manufacturing: On the critical path to vaccine access fact sheet
 

CVIA at upcoming events

3rd International Symposium on ‘Streptococcus algalactiae’ Disease (ISSAD)
October 16 to 18, 2023
Rio de Janeiro, Brazil

17th TechNet Conference
October 16 to 19, 2023
Panama City, Panama

American Society of Tropical Medicine & Hygiene Annual Meeting
October 18 to 22, 2023
Chicago, Illinois, USA

Meningitis Research Foundation Conference 2023
November 7 to 8, 2023
London, United Kingdom

11th European & Developing Countries Clinical Trials Partnership (EDCTP) Forum
November 7 to 10, 2023
Paris, France

14th African Rotavirus Symposium
November 8 to 10, 2023
Abuja, Nigeria
 

New scientific publications

Enabling accelerated vaccine roll-out for Public Health Emergencies of International Concern (PHEICs): Novel Oral Polio Vaccine type 2 (nOPV2) experience

Exploring Shigella vaccine priorities and preferences: Results from a mixed-methods study in low- and middle-income settings

Genetic stabilization of attenuated oral vaccines against poliovirus types 1 and 3

Impact and cost-effectiveness of alternative human papillomavirus vaccines for preadolescent girls in Mozambique: A modeling study

Impact and cost-effectiveness of strategies to prevent respiratory syncytial virus (RSV) disease in Vietnam: A modeling study

Impact, cost-effectiveness, and budget implications of HPV vaccination in Kenya: A modeling study

Meningococcal ACWYX conjugate vaccine in 2-to-29-year-olds in Mali and Gambia

Rotavirus vaccine product switch in Ghana: An assessment of service delivery costs, switching costs, and cost-effectiveness

Seasonal vaccination with RTS,S/AS01E vaccine with or without seasonal malaria chemoprevention in children up to the age of 5 years in Burkina Faso and Mali: A double-blind, randomized, controlled, Phase 3 trial