The acquisition and maintenance of antibodies to merozoite antigens of Plasmodium falciparum and their role in protective immunity to malaria

Mugyenyi, Cleopatra Kama (2010). The acquisition and maintenance of antibodies to merozoite antigens of Plasmodium falciparum and their role in protective immunity to malaria. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000ed6a

Abstract

Measurement of antibodies at a single time point in malaria-endemic populations and associating them with protection and susceptibility has given insight into the development and maintenance of the immune response to malaria. Immunity to malaria is a dynamic process that takes place over a number of years in different stages, which implies that antibody measurement at a single time point may not adequately encompass acquisition of immunity.

Antibody responses to merozoite antigens (AMA 1 and MSP2) were measured in 300 children aged 0-10 years twice a year for three years. Each child was followed up on a weekly basis for episodes of malaria. Factors affecting antibody responses at each time point and antibody contributions to protection from malaria were investigated, and the association between functional activity of anti-AMA 1 antibodies and protection was assessed.

Anti-AMA 1 and anti-MSP2 antibody responses were dependent on the amount of prior and ongoing exposure and paralleled the decline in malaria transmission that occurred during the study period. High antibody responses were generated after 2-3 episodes of parasitemia and were likely to drop on further exposure. There was no evidence for polarisation of IgG responses to AMA 1. The association between antibody responses and protection/risk of malaria was dependent on both the sample time and analysis method used. Antibody responses to AMA 1(W2mef) were associated with an increased risk of malaria over the study period. Antibodies to MSP2(3D7) may be associated with protection from malaria. Antibodies to a functional invasion inhibitory epitope of AMA 1(3D7) were rare but associated with protection from malaria.

Longitudinal assessment of antibody levels gives a more complete picture of acquisition and maintenance of malaria immunity. Antibodies can be both a measure of protection or susceptibility. These findings enrich knowledge on acquisition of immunity and will impact vaccination development and immunisation strategies.