Sustained peptide-specific gamma interferon T-cell response in rhesus macaques immunized with human immunodeficiency virus gag DNA vaccines.
We examined the influence of dose and method of antigen delivery on the dynamics and durability of T-cell responses to candidate human immunodeficiency virus (HIV) vaccines. Codon-optimized sequences from the HIV gag gene were inserted into alternative DNA vaccine vectors to express the coding sequence with or without the tissue plasminogen activator leader sequence. We delivered the vaccines by intramuscular injection as plasmid DNA without adjuvant or as plasmid DNA formulated with a novel block copolymer adjuvant (CRL8623) and then monitored the ensuing T-cell responses by using a gamma interferon enzyme-linked immunospot assay. We demonstrated persistence of the cell-mediated immune (CMI) response in rhesus macaques for at least 18 months following a four-dose vaccination regimen. The plasmid vaccine, with or without CRL8623, was immunogenic in macaques; however, the form coadministered with adjuvant exhibited improved T-cell responses, with a bias toward more antigen-specific CD8(+) T cells. Finally, we examined the fine specificity of the T-cell response to the gag vaccines by testing the response of 23 vaccinated macaques to individual Gag 20-mer peptides. Collectively, the monkeys responded to 25 epitopes, and, on average, each monkey recognized a minimum of 2.7 epitopes. The results indicate that a broad and durable CMI response to HIV DNA vaccines can be induced in a relevant nonhuman primate model.
Department of Virus and Cell Biology, Merck Research Laboratories, West Point, Pennsylvania 19486, USA. michael_caulfield@merck.com
Michael J
MJ
Caulfield
Su
S
Wang
Jeffrey G
JG
Smith
Timothy W
TW
Tobery
Xu
X
Liu
Mary-Ellen
ME
Davies
Danilo R
DR
Casimiro
Tong-Ming
TM
Fu
Adam
A
Simon
Robert K
RK
Evans
Emilio A
EA
Emini
John
J
Shiver
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D015683:Gene Products, gag / Q000276:immunology*; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis*; D008253:Macaca mulatta; D013601:T-Lymphocytes / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*
D016915:AIDS Vaccines; D015683:Gene Products, gag; D019444:Vaccines, DNA; D007371:Interferon-gamma