Development of a universal vaccine against malaria using protocols of heterologous prime-boost with replication-deficient human adenoviral vector type 5 expressing the immunodominant epitopes of the different allelic forms of CS antigen

Abstract

Plasmodium vivax is the second species more prevalent of malaria in the world. Recent data shows that 180-400 million cases occur approximately annually. In the Americas, the P. vivax is responsible for more than 70% of the cases of malaria. Inefficient measures of control used currently demand the development of new strategies of prevention such as vaccines, new drugs, and new insecticides. The project has as its main objective to evaluate the immunogenicity of a universal vaccine against malaria caused by the P. vivax using the protocol of heterologous "prime-boost". The first dose will be a replication-deficient recombinant adenovirus in human response of type 5 (AdHu5) expressing the circumsporozoite protein of Plasmodium vivax. For this purpose, we will use the AdHu5-PvCS containing the synthetic gene of the CS protein of P. vivax that express the immunodominant epitope of the three allelic forms fused in the same polypeptide. The AdHu5-PvCS will be tested for expression in mammal cells after infection in vitro of cells. After the validation of the expression of the transgenic product by immunoblotting, the adenovirus will be expanded in cells HEK 293 and used in heterologous "prime-boost" vaccination protocols of isogenic mice. "Prime" will be made by the immunization with the adenovirus and "boost" will be a combination of recombinant proteins of the three variants of P. vivax. After the immunizations, the sera of the animals will be collected for analysis of the humoral immune response.(AU)