A multigene HIV type 1 subtype C modified vaccinia Ankara (MVA) vaccine efficiently boosts immune responses to a DNA vaccine in mice.
Heterologous prime-boost vaccine strategies have generated high frequencies of antigen-specific T cells in preclinical and clinical trials of candidate HIV vaccines. We have developed a DNA (SAAVI DNA-C) and MVA (SAAVI MVA-C) vaccine based on HIV-1 subtype C for testing in clinical trials. Both vaccines contain five subtype C genes: gag, reverse transcriptase, tat, and nef, expressed as a polyprotein, and a truncated env (gp150). The individual vaccines induced CD8(+) and CD4(+) T cells specific for the vaccine-expressed antigens in BALB/c mice. Combining the vaccines in a DNA prime and MVA boost regimen increased the cumulative peptide response compared to the DNA vaccine alone 10-fold, to over 6000 SFU/10(6) splenocytes in the IFN-gamma ELISPOT assay. Th1 cytokine IFN-gamma and TNF-alpha levels from HIV-specific CD8(+) and CD4(+) T cells increased 20- and 8-fold, respectively, with a SAAVI MVA-C boost. Effector and effector memory RT- and Env-specific memory CD8(+) T cell subsets were boosted after MVA immunization, and over time the cells returned to an intermediate memory phenotype similar to that prior to the boost. Immunization of guinea pigs with the DNA-MVA combination induced high titers of antibodies to gp120, although neutralizing activity was weak or absent. The demonstration that these vaccines induce potent cellular immune responses merits their testing in clinical trials.
Shephard
Enid
E
Institute of Infectious Disease and Molecular Medicine and Division of Medical Virology, Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town, South Africa.
Burgers
Wendy A
WA
Van Harmelen
Joanne H
JH
Monroe
James E
JE
Greenhalgh
Trish
T
Williamson
Carolyn
C
Williamson
Anna-Lise
AL
D016915:AIDS Vaccines / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005838:Genotype; D006168:Guinea Pigs; D015483:HIV Antibodies / Q000097:blood; D015497:HIV-1 / Q000235:genetics*; D007117:Immunization, Secondary; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019444:Vaccines, DNA / Q000235:genetics* / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000382:microbiology; D014616:Vaccinia virus / Q000235:genetics*
D016915:AIDS Vaccines; D015483:HIV Antibodies; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D007371:Interferon-gamma