Journal of Antivirals & Antiretrovirals
Open Access
ISSN: 1948-5964
ISSN: 1948-5964
Gilma S�nchez-Burgos, Jos� Ramos-Casta�ed, Roberto Cedillo-Rivera1 and Eric Dumonteil
Scientific Tracks Abstracts: JAA
We used T cell epitope prediction tools to identify epitopes from a representative sample of Dengue virus (DENV) polyprotein sequences, and evaluated in vivo and in vitro the immunogenicity and antigenicity of the corresponding synthetic vaccine candidates. Balb/c mice were immunized subcutaneously with 5 distinct synthetic peptides (50μg each) in Freund?s complete adjuvant (v/v). Two weeks later, mice received a second dose of the same peptide in Freud?s incomplete adjuvant. Mock immunized mice only received doses of the same adjuvants. Th ree weeks aft er the last immunization, mice were sacrifi ced to collect blood and spleen cells for the analysis of the immune response. In subsequent experiments, mice were immunized with subsets of 9-11 peptides mixtures as described above, for confi rmation of their immunogenicity. Twenty two epitopes were predicted to have a high affi nity for MHC class I (H-2Kd, H-2Dd, H-2Ld alleles) or class II (IAd alleles). Th ese epitopes were conserved between the four virus serotypes, but with no similarity to human and mouse sequences. Th irteen synthetic peptides induced specifi c antibodies production with or without T cells activation in mice. Th ree synthetic peptides induced mostly IgG antibodies, and one of these from the E gene induced a neutralizing response. Ten peptides induced a combination of humoral and cellular responses by CD4+ and CD8+ T cells. Twelve peptides were novel B and T cell epitopes. Th ese results indicate that our bioinformatics strategy is a powerfull tool for the identifi cation of novel antigens and its application to human HLA may lead to a potent epitope-based vaccine against Dengue virus and many other pathogens.