A Phylogenetic Study On Immunization Strategy Of Replicating Poxvirus Vector Vaccine

AIDS has become a serious public health threat to the people in the world.Safe and effective HIV vaccine may be the best weapon to control HIV transmission.The clinical trials show that effective HIV vaccines may need to induce more balanced humoral and cellular immune responses.The heterogeneous prime-boost immunization strategy is one of the most potential strategies to induce HIV protective immunity.This study was based on the replicating poxvirus vector vaccine rTV and TTK-EG.Three prime-boost strategies were studied,including replicating poxvirus vector vaccine priming-protein vaccine boosting,DNA vaccine priming-replicating poxvirus vector vaccine boosting,DNA vaccine priming-replicating poxvirus vector vaccine/protein vaccine boosting.The influencec of different intervals between 2 doses of replicating poxvirus vector vaccine with or without protein vaccine(8 weeks,12 weeks or 16 weeks)on the immune responses were further studied.The results showed that,in the rTV prime-gp140/p55 boost regimen,the immunization interval had no significant effect on the cellular immune response,and the geometric average titers of HIV-1 p55 antibody in the 12-week-interval group was 105.44,which was significantly higher than that of the 16-week-interval group;in the DNA prime-rTV boost regimen,the 16-week-interval group could induce high levels of humoral and cellular immune responses,and the geometric average titers of HIV-1 V1V2-gp70 antibody was 104.41,the CD8 + T cell ratio of secretion of IFN-?,TNF-a were 0.86%and 1.01%,respectively;in the DNA prime-rTV/gp140 boost regimen,the 12-week-interval group could induce high levels of humoral and cellular immune responses,and the geometric average titers of HIV-1 gp140 antibody was 105'93,the CD4+ and CD8 + T cell ratio of secretion of IFN-y were 0.29%and 0.39%,respectively.In the TTK-EG prime-gp140/p55 boost regimen,the geometric average titers of HIV-1 V1V2-gp70 antibody in the 16-week-interval group was significantly enhanced,which reached to 104.32;in the DNA prime-TTK-EG boost regimen,the 8-week-interval group could induce high levels of CD4+ T cell immune response,which the CD4+ T cell ratio of secretion of IFN-?,TNF-a were 0.91%and 0.89%,respectively,and the 16-week-interval group could induce high levels of CD8+ T cell immune response,which the CD8+ T cell ratio of secretion of IFN-?,TNF-? were 0.64%and 0.75%,respectively;in the DNA prime-TTK-EG/gp140 boost regimen,the geometric average titers of HIV-1 V1 V2-gp70 antibody in the 16-week-interval group was significantly enhanced,which reached to 104.23,and the CD8+ T cell ratio of secretion of IFN-?,TNF-a were 0.33%and 0.46%,respectively.Bisides,the specific H-2d restricted T-cell epitopes(HIV-1 Env and Gag)of BALB/c(H-2d)mice immunized with TTK-EG twice intracutaneously were further studied.The results showed that,two Env-specific(gp 140-9,AYDTEVHNVWATHACVPA,aa 60-77;gp 140-74,IVQQQSNLLRAIEAQQHL,aa 548-565)and three Gag-specific(Gag-49,AAMQILKDTINEEAA,aa 196-210;Gag-64,VPVGDIYKRWIILGL,aa 256-270;Gag-65,DIYKRWIILGLNKIV,aa 260-274)peptides were identified containing HIV-1 specific T-cell epitopes,and gpl40-74(IVQQQSNLLRAIEAQQHL,aa 548-565)was first discovered containing H-2d restricted T-cell epitopes.The ability to stimulate HIV specific CD8+ T cells secreting IFN-?,IL-2 and TNF-? cytokines between the immunodominant epitope peptides and all-peptide pools is comparative.