Abstract
Plasmodium falciparum PfRH5 protein binds Ripr, CyRPA and Pf113 to form a complex that is essential for merozoite invasion of erythrocytes. The inter-genomic conservation of the PfRH5 complex proteins makes them attractive blood stage vaccine candidates. However, little is known about how antibodies to PfRH5, CyRPA and Pf113 are acquired and maintained in naturally exposed populations, and the role of PfRH5 complex proteins in naturally acquired immunity. To provide such data, we studied 206 Ghanaian children between the ages of 1–12 years, who were symptomatic, asymptomatic or aparasitemic and healthy. Plasma levels of antigen-specific IgG and IgG subclasses were measured by ELISA at several time points during acute disease and convalescence. On the day of admission with acute P. falciparum malaria, the prevalence of antibodies to PfRH5-complex proteins was low compared to other merozoite antigens (EBA175, GLURP-R0 and GLURP-R2). At convalescence, the levels of RH5-complex-specific IgG were reduced, with the decay of PfRH5-specific IgG being slower than the decay of IgG specific for CyRPA and Pf113. No correlation between IgG levels and protection against P. falciparum malaria was observed for any of the PfRH5 complex proteins. From this we conclude that specific IgG was induced against proteins from the PfRH5-complex during acute P. falciparum malaria, but the prevalence was low and the IgG levels decayed rapidly after treatment. These data indicate that the levels of IgG specific for PfRH5-complex proteins in natural infections in Ghanaian children were markers of recent exposure only.
Highlights
P. falciparum malaria is estimated to cost more than half a million lives every year, mainly in tropical Africa [1]
We analyze antibodies specific for three potential blood stage malaria vaccine candidates
PfRH5 specific antibody levels in Kenyan children were measured before and after the rainy season. It was clear, that malaria exposure did boost the level of PfRH5 antibodies, but there was no follow up sample to determine the decay or maintenance of the antibody titres
Summary
P. falciparum malaria is estimated to cost more than half a million lives every year, mainly in tropical Africa [1]. The disease burden is highly concentrated among young children, because survivors gradually acquire protective immunity in response to repeated infection [2] Protection acquired this way is notoriously sluggish to develop, is incomplete, and has limited durability. These characteristics have mainly been related to the extensive polymorphism and antigenic variation in the parasite’s asexual blood-stage antigens that are the key targets of naturally acquired immunity to the disease. Many consider these features as insurmountable obstacles to the development of vaccines targeting this part of the parasite life cycle, but the recent discovery of a set of conserved antigens that appear indispensable for completion of the asexual multiplication cycle has raised new hopes. Much has been learned about the function of PfRH5 in invasion, and several additional parasite molecules that play important roles in it have been identified
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