Professor Francis Ndungu
Immune response against malaria
Malaria vaccines created in Europe or America might work well for naïve individuals but not in endemic areas. Immune responses to malaria differ in naïve or exposed, or historically-exposed populations; in endemic regions some people become immune to malaria. Understanding naturally acquired immunity to malaria aims to inform the development of better malaria vaccines.
Honorary Visiting Research Fellow
- Head of Cellular Immunology Group
I am a malaria immunologist interested in understanding of how semi-immune individuals control malaria parasite growth and the associated inflammation (symptoms) – and the potential translation of that knowledge in the development of effective malaria vaccines.
My group has demonstrated that malaria drives expansions of atypical lymphocytes, whose normal function appears impaired. We also found that CD4 T cells from currently exposed children proliferate far more less and produce more anti-inflammatory cytokines than those from historically infected children (“exposed in the past but subsequently lived for several years without malaria before the study”), after stimulation with total Plasmodium falciparum antigen in vitro. Others have shown that immune responses to malaria vaccines in malaria exposed individuals are reduced in magnitude (relative to malaria naïve adults in America/Europe). Intriguingly, semi-immune individuals can still control parasite densities and levels of inflammation (via mechanisms that remain poorly defined), in spite the reduced immune responsiveness.
Together, these observations suggest that malaria induces an “immune-regulatory state” that may be critical for natural immunity but impedes vaccine immunogenicity, and my current work is describing the mechanisms of this immune-regulation and immune-control in human malaria. These studies are based on long-term longitudinal cohorts of children living with P falciparum malaria, and in semi-immune adults experimentally infected with the same species of malaria parasites at the KEMRI/Wellcome Research Programme, Kilifi, Kenya.
The studies will provide the much-needed insight into how we can induce protective immune responses by vaccination in the background of the immune-regulatory state induced by natural exposure in endemic areas.
Huttner A. et al, (2023), Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
Kimotho J. et al, (2023), Wellcome Open Research, 8, 350 - 350
Odera DO. et al, (2023), Science translational medicine, 15
Mugo RM. et al, (2023), PloS one, 18
Kapulu MC. et al, (2022), BMC Infectious Diseases, 22