Immunogenicity of a malaria vaccine candidate based on allelic forms of the Plasmodium vivax circumsporozoite antigen administered in mice using different adjuvant formulations.

Background Plasmodium vivax is the most common species that cause malaria outside of the African continent. The development of an efficacious vaccine would contribute greatly to control malaria transmission. Recently, using bacterial and adenoviral recombinant proteins based on the P. vivax circumsporozoite protein (PvCSP), we demonstrated the possibility of eliciting strong antibody-mediated immune responses to each of the three allelic forms of PvCSP. The present study was designed to evaluate the immunogenicity of a hybrid polypeptide named PvCSP-All epitopes in the presence of adjuvants applicable for human use. This hybrid containing the conserved C-terminus of the PvCSP, and the three variant repeat domains (VK210, VK247, and P. vivax-like) produced in the yeast Pichia pastoris. Material and Methods C57BL/6 mice were immunized subcutaneously with 10 g of the antigen in the presence of adjuvants Polyriboinosinic:polyribocytidylic acid (PolyI:C), Montanide® ISA 720 and squalene-based adjuvants (AddaVaxTM and MF59). The IgG antibodies against the three P. vivax CS proteins were determined by ELISA in sera from mice two weeks after each immunizing dose. Results and Conclusion Mice immunized with PvCSP-All generated high IgG titres specific to all CSP alleles. Our results demonstrated that it is possible to elicit a strong humoral response to PvCSP alleles in mice in the presence of different adjuvants, including a TLR-3 agonist. Among the tested formulations, the adjuvants Poly(I:C) and Montanide ISA 720 were more immunogenic after two doses, therefore more promising for pre-clinical trials in non-human primates. Financing: FAPESP 2012/13032-5 and 2014/18102-7, CNPq-INCTV, CAPES.