Development of strategies to increase the immunogenicity of the DNA vaccine HIVBr18 based on fusion with gD protein of human herpes virus type 1 (HSV-1) and coadministration of cytokines.

Abstract

The Acquired Immune Deficiency Syndrome (AIDS), caused by HIV (Human Immunodeficiency Virus) is a sexually transmitted disease, acquired through contact with blood and blood products and capable of maternal-fetal transmission. The HIV-1 has reached nearly 35 million people, with nearly three million new cases and two million deaths each year. Despite the advances in understanding the pathogenesis of the disease and the immune response to infection, there is no effective vaccine against HIV. However a vaccine strategy developed entirely in Brazil has shown promising results. The research group led by Prof. Edecio Cunha Neto develops a vaccine formulation based on DNA vaccines encoding eighteen CD4 promiscuous and conserved epitopes of HIV-1, called HIVBr18. These epitopes were identified using the prediction algorithm TEPITOPE. Recognition analysis of these epitopes by ELISPOT assays showed that all 18 peptides used were recognized by peripheral blood mononuclear cells (PBMC) of patients in different stages of HIV infection. After immunization of HLA class II transgenic mice using this DNA vaccine, it was able to verify the secretion of IFN-³ and activation and proliferation of CD4 + and CD8 + cells against multiple epitopes encoded by the vaccine. However the search for more immunogenic formulations that confer more robust responses, since it gives more chances to this formulation to be successful in future studies, is essential. In this way, the fusion of antigens to immune modulator proteins may increase the immunogenicity of certain DNA vaccines. Among the research lines of group led by Prof. Luis Carlos de Souza Ferreira, the study of immunological properties resulting from the fusion of epitopes to the sequence encoding the glycoprotein D (gD) of Human Herpes virus type 1 (HSV-1) highlights. The fusion of E7 protein of human papillomavirus type 16 (HPV-16) to gD of HSV-1 resulted in a dramatic increase in cellular response based on CD8 + T cells and generate a protective response against tumors induced by HPV-16 in immunized mice. So through the fusion between gD and the polyepitope Br18 we will be able to evaluate the immunomodulatory properties resulting from this merge in relation to the magnitude of immune response generated and breadth of recognition of epitopes encoded by this formulation. Moreover the use of plasmids encoding cytokines will be used as molecular adjuvants co-administered with this new formulation that will be developed.