A reduced risk of infection with Plasmodium vivax and clinical protection against malaria are associated with antibodies against the N terminus but not the C terminus of merozoite surface protein 1.

Progress towards the development of a malaria vaccine against Plasmodium vivax, the most widely distributed human malaria parasite, will require a better understanding of the immune responses that confer clinical protection to patients in regions where malaria is endemic. The occurrence of clinical protection in P. vivax malaria in Brazil was first reported among residents of the riverine community of Portuchuelo, in Rondônia, western Amazon. We thus analyzed immune sera from this same human population to determine if naturally acquired humoral immune responses against the merozoite surface protein 1 of P. vivax, PvMSP1, could be associated with reduced risk of infection and/or clinical protection. Our results demonstrated that this association could be established with anti-PvMSP1 antibodies predominantly of the immunoglobulin G3 subclass directed against the N terminus but not against the C terminus, in spite of the latter being more immunogenic and capable of natural boosting. This is the first report of a prospective study of P. vivax malaria demonstrating an association of reduced risk of infection and clinical protection with antibodies against an antigen of this parasite.

Variant proteins of Plasmodium vivax are not clonally expressed in natural infections.

Plasmodium vivax is the most widely distributed human malaria parasite and responsible for 70-80 million clinical cases each year and a large socio-economical burden. The sequence of a chromosome end from P. vivax revealed the existence of a multigene superfamily, termed vir (P. vivax variant antigens), that can be subdivided into different subfamilies based on sequence similarity analysis and which represents close to 10-20% of the coding sequences of the parasite. Here we show that there is a vast repertoire of vir genes abundantly expressed in isolates obtained from human patients, that different vir gene subfamilies are transcribed in mature asexual blood stages by individual parasites, that VIR proteins are not clonally expressed and that there is no significant difference in the recognition of VIR-tags by immune sera of first-infected patients compared with sera of multiple-infected patients. These data provide to our knowledge the first comprehensive study of vir genes and their encoding variant proteins in natural infections and thus constitute a baseline for future studies of this multigene superfamily. Moreover, whereas our data are consistent with a major role of vir genes in natural infections, they are inconsistent with a predominant role in the strict sense of antigenic variation.