Exploiting cross-reactive, conserved epitopes in Plasmodium vivax to develop a vaccine against falciparum placental malaria

Objectives

The long-term goal of this project is to develop an alternative approach to a vaccine against pregnancy-associated malaria that targets highly conserved, subdominant (even cryptic) epitopes. What is unique about this approach is that it exploits a mechanism of cross- species immunity, where epitopes from one Plasmodium species elicit robust, broadly neutralizing antibodies against structurally related antigens from another species. 

This goal to develop a vaccine to protect pregnant women from falciparum placental malaria that is based on the cross- reactive epitope in vivax SD1 will be achieved through three complementary specific aims:

• Epitopes required to elicit functional, cross-reactive antibodies will be identified in Aim 1 through conformationally constricted peptide microarrays screened with mouse monoclonal antibodies (mAbs) and human mAbs to SD1 isolated from Colombian study populations.
• Epitopes will be synthesized as peptide- conjugates or within engineered recombinant domains, and immunogenicity will be optimized in Aim 2 to produce antibodies with functional activity against parasites that express diverse alleles of var2csa.
• In the third Aim, the cryptic epitopes in VAR2CSA recognized by these antibodies will be mapped to identify the targets of antibodies elicited by an SD1-derived vaccine.

The integration of these findings will provide important insight into the mechanism of cross-species epitope recognition, which will serve as the basis for a vivax vaccine against falciparum placental malaria and could be applied more broadly to vaccines against other malaria antigens.