Immunization with different PfAMA1 alleles in sequence induces clonal imprint humoral responses that are similar to responses induced by the same alleles as a vaccine cocktail in rabbits

Abstract

<p>Abstract</p> <p>Background</p> <p>Antibodies to key <it>Plasmodium falciparum </it>surface antigens have been shown to be important effectors that mediate clinical immunity to malaria. The cross-strain fraction of anti-malarial antibodies may however be required to achieve</p> <p>strain-transcending immunity. Such antibody responses against <it>Plasmodium falciparum </it>apical membrane antigen 1 (<it>Pf</it>AMA1), a vaccine target molecule that is expressed in both liver and blood stages of the parasite, can be elicited through immunization with a mixture of allelic variants of the parasite molecule. Cross-strain antibodies are most likely elicited against epitopes that are shared by the allelic antigens in the vaccine cocktail.</p> <p>Methods</p> <p>A standard competition ELISA was used to address whether the antibody response can be further focused on shared epitopes by exclusively boosting these common determinants through immunization of rabbits with different <it>Pf</it>AMA1 alleles in sequence. Th<it>e in vitro </it>parasite growth inhibition assay was used to further evaluate the functional effects of the broadened antibody response that is characteristic of multi-allele vaccine strategies.</p> <p>Results</p> <p>A mixed antigen immunization protocol elicited humoral responses that were functionally similar to those elicited by a sequential immunization protocol (p > 0.05). Sequential exposure to the different <it>Pf</it>AMA1 allelic variants induced immunological recall of responses to previous alleles and yielded functional cross-strain antibodies that would be capable of optimal growth inhibition of variant parasites at high enough concentrations.</p> <p>Conclusions</p> <p>These findings may have implications for the current understanding of the natural acquisition of clinical immunity to malaria as well as for rational vaccine design.</p