DNA gag/adenovirus type 5 (Ad5) gag and Ad5 gag/Ad5 gag vaccines induce distinct T-cell response profiles.
Results from Merck's phase II adenovirus type 5 (Ad5) gag/pol/nef test-of-concept trial showed that the vaccine lacked efficacy against human immunodeficiency virus (HIV) infection in a high-risk population. Among the many questions to be explored following this outcome are whether (i) the Ad5 vaccine induced the quality of T-cell responses necessary for efficacy and (ii) the lack of efficacy in the Ad5 vaccine can be generalized to other vector approaches intended to induce HIV type 1 (HIV-1)-specific T-cell responses. Here we present a comprehensive evaluation of the T-cell response profiles from cohorts of clinical trial subjects who received the HIV CAM-1 gag insert delivered by either a regimen with DNA priming followed by Ad5 boosting (n = 50) or a homologous Ad5/Ad5 prime-boost regimen (n = 70). The samples were tested using a statistically qualified nine-color intracellular cytokine staining assay measuring interleukin-2 (IL-2), tumor necrosis factor alpha, macrophage inflammatory protein 1beta, and gamma interferon production and expression of CD107a. Both vaccine regimens induced CD4(+) and CD8(+) HIV gag-specific T-cell responses which variably expressed several intracellular markers. Several trends were observed in which the frequencies of HIV-1-specific CD4(+) T cells and IL-2 production from antigen-specific CD8(+) T cells in the DNA/Ad5 cohort were more pronounced than in the Ad5/Ad5 cohort. Implications of these results for future vaccine development will be discussed.
Cox
Kara S
KS
Department of Vaccine Basic Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA. Kara_cox@merck.com
Clair
James H
JH
Prokop
Michael T
MT
Sykes
Kara J
KJ
Dubey
Sheri A
SA
Shiver
John W
JW
Robertson
Michael N
MN
Casimiro
Danilo R
DR
D016915:AIDS Vaccines / Q000378:metabolism; D000256:Adenoviridae / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D054407:Chemokine CCL4 / Q000096:biosynthesis; D015331:Cohort Studies; D004247:DNA / Q000378:metabolism; D015750:Genes, gag / Q000235:genetics*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D052118:Lysosomal-Associated Membrane Protein 1 / Q000096:biosynthesis; D008954:Models, Biological; D010641:Phenotype; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016915:AIDS Vaccines; D054407:Chemokine CCL4; D007376:Interleukin-2; D052118:Lysosomal-Associated Membrane Protein 1; D014409:Tumor Necrosis Factor-alpha; D004247:DNA