Plasmodium vivax is the most widespread, and the second most prevalent, species causing malaria in the world. Current measures used to control the transmission of this disease would benefit from the development of an efficacious vaccine. In the case of the deadly parasite P. falciparum, the recombinant RTS,S vaccine containing the circumsporozoite (CSP) antigen consistently protects between 30-50% of human volunteers against infection and is undergoing Phase III clinical trials in Africa with similar efficacy. These findings encouraged us to develop a P. vivax vaccine containing the three circulating allelic forms of the P. vivax CSP. Toward this goal, we generated 3 recombinant bacterial proteins representing ... More
Plasmodium vivax is the most widespread, and the second most prevalent, species causing malaria in the world. Current measures used to control the transmission of this disease would benefit from the development of an efficacious vaccine. In the case of the deadly parasite P. falciparum, the recombinant RTS,S vaccine containing the circumsporozoite (CSP) antigen consistently protects between 30-50% of human volunteers against infection and is undergoing Phase III clinical trials in Africa with similar efficacy. These findings encouraged us to develop a P. vivax vaccine containing the three circulating allelic forms of the P. vivax CSP. Toward this goal, we generated 3 recombinant bacterial proteins representing the CSP alleles as well as a hybrid polypeptide called PvCSP-All CSP epitopes. This hybrid contains the conserved N- and C-terminus of the P. vivax CSPs and the three variant repeat domains in tandem. We also generated simian and human recombinant replication-defective adenovirus vectors expressing PvCSP-All CSP epitopes. Mice immunized with the mixture of recombinant proteins in a formulation containing the adjuvant poly(I:C) developed high and long lasting serum IgG titers comparable to those elicited by proteins emulsified in complete Freund's adjuvant. Antibody titers were similar in mice immunized with homologous (protein/protein) or heterologous (adenovirus/protein) vaccine regimens. The antibodies recognized the three allelic forms of CSP, reacted to the repeated and non-repeated regions of CSP and recognized sporozoites expressing the alleles VK210 and VK247. The vaccine formulations described in this work should be useful for the further development of an anti-P. vivax vaccine.
