Abstract
Many studies on the role of merozoite surface protein 3 (MSP3) in immunity against malaria have focused on a conserved section of MSP3. New evidence suggests that polymorphic sequences within MSP3 are under immune selection. We report a detailed analysis of naturally-acquired antibodies to allele-specific and conserved parts of MSP3 in a Kenyan cohort. Indirect and competition ELISA to heterologous recombinant MSP3 proteins were used for antibody assays, and parasites were genotyped for msp3 alleles. Antibody reactivity to allele-specific and conserved epitopes of MSP3 was heterogenous between individuals. Overall, the prevalence of allele-specific antibody reactivity was significantly higher (3D7-specific 54%, K1-specific 41%) than that to a recombinant protein representing a conserved portion of C-terminal MSP3 (24%, P < 0·01). The most abundant IgG subclass was IgG3, followed by IgG1. Allele-specific reactivity to the K1-type of MSP3 was associated with a lower risk of clinical malaria episodes during a 6-month follow-up in individuals who were parasitized at the start of the malaria transmission season (Relative risk 0·41 with 95% confidence interval 0·20–0·81, P = 0·011). The potential importance of allele-specific immunity to MSP3 should be considered in addition to immunity to conserved epitopes, in the development of an MSP3 malaria vaccine.
Highlights
Recent estimates of the global burden of malaria indicate that about 515 million clinical attacks were attributable to Plasmodium falciparum in 2002, with the majority (70%) of these episodes occurring in Africa [1] where young children account for 90% of all malaria deaths [2]
We investigated the prevalence of allele-specific and conserved antibodies to Escherichia coli expressed recombinant merozoite surface protein 3 (MSP3) proteins, and determined whether these antibodies were associated with protection in a longitudinal study in a rural community in Kenya
There was a correlation between the reactivity of antibodies to the MSP3 full-length antigens 3D7 MSP3 and K1 MSP3 in the indirect ELISA, pair wise correlation coefficient 0·6752, P = 0·0000, n = 536 (Figure 1)
Summary
Recent estimates of the global burden of malaria indicate that about 515 million clinical attacks were attributable to Plasmodium falciparum in 2002, with the majority (70%) of these episodes occurring in Africa [1] where young children account for 90% of all malaria deaths [2]. Understanding the naturally acquired immunity (NAI) to malaria that is evident in older children and adults living in endemic areas is important for the selection of realistic vaccine targets and provides a reference against which the effectiveness of new vaccines can be compared. The mechanisms underlying NAI are incompletely understood, there is strong evidence to suggest that antibodies are centrally important [4,5]. Red cell invasion is a critical point in the life cycle of parasite at which merozoites are briefly exposed to the host immune system and can be targeted by antibodies. Occurring antibodies to many merozoite recombinant antigens have been demonstrated in malaria endemic populations. Some of these antigens are currently under development as components of experimental vaccines
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