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Journal of Virology, October 2002, p. 10038-10043, Vol. 76, No. 19
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.19.10038-10043.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Sustained Peptide-Specific Gamma Interferon T-Cell Response in Rhesus Macaques Immunized with Human Immunodeficiency Virus gag DNA Vaccines

Michael J. Caulfield,1* Su Wang,1 Jeffrey G. Smith,1 Timothy W. Tobery,1 Xu Liu,1 Mary-Ellen Davies,2 Danilo R. Casimiro,2 Tong-Ming Fu,2 Adam Simon,1 Robert K. Evans,3 Emilio A. Emini,1,2 and John Shiver2

Departments of Virus and Cell Biology,1 Viral Vaccine Research,2 Vaccine Pharmaceutical Research, Merck Research Laboratories, West Point, Pennsylvania 194863

Received 20 March 2002/ Accepted 30 June 2002

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.

* Corresponding author. Mailing address: Merck Research Labs, Department of Virus and Cell Biology, WP26B, 770 Sumneytown Pike, West Point, PA 19034. Phone: (215) 652-3402. Fax: (215) 652-2142. E-mail: michael_caulfield{at}merck.com.

Journal of Virology, October 2002, p. 10038-10043, Vol. 76, No. 19
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.19.10038-10043.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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