R21 and RH5.1 cellular immunology in endemic settings published in Frontiers in Immunology
We’re pleased to report the publication in Frontiers in Immunology of our most recent exploratory cellular work conducted by former PhD candidate Caroline Bundi, now graduate, under the supervision of Carolyn M Nielsen , Katie J Ewer, Melissa C Kapulu and Ally I Olotu . The work and the Caroline’s PhD fellowship, was conducted under the Multi-Stage Malaria Vaccine Consortium (MMVC), NCT03580824 funded by the European and Developing Countries Clinical Trials Partnership (EDCTP2) programme supported by the European Union (RIA2016V-1649).
Lay Abstract: In this study, we investigated how two malaria vaccines—R21/Matrix-M®, which targets the parasite before it enters red blood cells, and RH5.1/Matrix-M®, which targets the parasite after it enters red blood cells—activate the immune system in people living in malaria-endemic areas of Kenya and Tanzania.
We focused on two types of immune cells that help the body produce and maintain protective antibodies: memory B cells, which "remember" the malaria parasite and can rapidly produce antibodies upon future exposure, and circulating T follicular helper (cTfh) cells, which help B cells develop and function effectively.
Our findings showed that both vaccines successfully stimulated these important immune cells. For the R21 vaccine, infants developed stronger vaccine-specific memory B-cell responses than adults, and higher doses of the Matrix-M adjuvant further enhanced these responses. We also found that individuals with higher levels of memory B cells and cTfh cells tended to have higher levels of malaria-specific antibodies.
For the RH5.1 vaccine, a delayed booster dose produced stronger memory B-cell responses than the standard monthly booster schedule, suggesting that adjusting the timing of booster vaccinations may improve long-term immunity. We also observed that children with greater previous exposure to malaria developed stronger RH5-specific cTfh-cell responses after vaccination, indicating that natural malaria exposure can influence how the immune system responds to vaccination.
Overall, our study demonstrates that both vaccines generate the immune responses needed to support durable antibody production. The strength of these responses is influenced by factors such as age, previous malaria exposure, vaccine formulation, and booster timing. These findings provide valuable insights for the design of future malaria vaccination strategies and support the development of combined vaccine approaches that target multiple stages of the malaria parasite's life cycle to achieve stronger and longer-lasting protection.
Access to the full text of the article can be found here https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1743327/full
