Completed Infection & Immunity Pregnancy, Children & Inherited Conditions

Integrated studies of the targets, regulation and consequences of human immunity to malaria.

In plain English

AI plain-English summary

In Kilifi, Kenya, researchers are tracking thousands of children over years to map exactly how human immunity to malaria works—and why it often fails. Malaria kills hundreds of thousands of people each year, mostly young children in Africa. The parasite that causes the disease is a master of disguise, changing its surface proteins to evade the immune system. Scientists know that people eventually develop some immunity after repeated infections, but they do not fully understand which parts of the parasite the immune system should target, or why immunity wanes when transmission drops. This project aims to fill those gaps. The team will identify the specific proteins on the merozoite—the invasive form of the parasite—that trigger protective immune responses. They will also characterise antigens on infected red blood cells that are linked to severe disease, and study the genetic changes in parasites exposed to different levels of immune pressure over decades. By combining mathematical modelling with next-generation sequencing of parasites, they will predict how changes in malaria transmission—for example, from control programmes—reshape both human immunity and parasite populations. This is fundamental science. It will not produce a vaccine or drug tomorrow. But understanding exactly which immune targets matter, and how the parasite evolves in response, provides the raw knowledge needed to design more effective vaccines and predict how malaria will behave as control efforts shift.

View original technical description
This proposal seeks support for an epidemiological and analytical framework developed by us over a number of years in Kilifi, Kenya. Specific elements include longitudinal monitoring of four cohorts of children with detection and careful phenotyping of clinical events in order to relate putative immune functions to immune status. It also includes a carefully documented historical archive of parasite and human samples allowing us to examine the population level consequences of changes in immun ity. Within this framework we will focus on (1) identifying immune targets on the merozoite by using sera of carefully defined immune status to probe both 2D gels and libraries of expressed merozoite proteins; (2) characterizing parasite-derived antigens on the surface of the infected red cell associated with low immunity and virulence; (3) identifying the mechanisms regulating the immune response to malaria; (4) determining which non-antigen genes are subject to immune selection through w hole-transcriptome and whole-genome comparisons of P. falciparum parasites from populations that have been under different intensities of immune selection pressure over a long period of time; and (5) determining the effects of changing transmission on human and parasite populations by a combination of mathematical modelling and next-generation parasite sequencing.

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Researchers

Kevin Marsh (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

A systems biology approach to understand immunity and pathogenesis of malaria in children
. Osier, KEMRI-CGMRC, Defining the merozoite targets of protective immunity against Plasmodium falciparum malaria through multi-centre cohort studies
Adaptive variation in sexual and asexual reproduction of endemic malaria parasites
Commitment, maturation and infectivity of sexual stage malaria parasites in natural infections
Structural studies of host-parasite interactions at the heart of malaria pathogenicity.

Original classification

Programme Grant

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