The natural history of immune responses to malaria

Abstract

Available evidence suggests that responses to the parasite-induced antigens on the surface of red cells infected by mature stages of P. falciparum (PIESA) confer variant-specific immunity against malaria. However, much of the available data are derived from cross-sectional or longitudinal studies restricted to a few weeks after a malaria episode. As such, the natural history of antibody responses to PIESA is poorly documented. I set up a longitudinal framework to examine the kinetics, dynamics, and protective efficacy of anti-PIESA responses in children in Kilifi. I also used the same the framework to explore responses to other schizont antigens. The majority of children mounted typical primary antibody responses against PIESA within two weeks of an acute episode and sustained the levels for more than 12 weeks. However, some children appear to have inadequate responses that failed to persist beyond twelve weeks. When followed up over a year period, all the children showed loss and acquisition of anti-PIESA specificities regardless of their disease experience during the period. This suggests that anti-PIESA response may be short-lived and this might be related to the predomination of the responses by short-half life IgG3 or with failure to switch from IgM to IgG. Anti-PIESA antibody responses to certain randomly selected parasite isolates were associated with protection from subsequent clinical episodes either independently or in synergy with concurrent malaria infection. However, this protection was not related to the relative frequency with which the target isolates appear to have been encountered by the children during the follow-up period. Besides anti-PIESA responses, possession of antibodies to a 192 kDa schizont antigen band on a Western blot was also associated with protection against clinical episodes of malaria. IgGl and IgG3 dominated responses to all the bands on the blot and for some antigens; IgG3 responses were present only in pooled plasma from immune but not non-immune individuals. More studies are necessary in order to understand further the kinetics and dynamics of antibody responses to PIESA and other schizont antigens and the mechanisms underlying the protection against malaria that they provide