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Journal of Virology, August 2000, p. 7485-7495, Vol. 74, No. 16
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Simian Immunodeficiency Virus (SIV) gag DNA-Vaccinated Rhesus Monkeys Develop Secondary Cytotoxic T-Lymphocyte Responses and Control Viral Replication after Pathogenic SIV Infection

Michael A. Egan,1,* William A. Charini,1 Marcelo J. Kuroda,1 Jörn E. Schmitz,1 Paul Racz,2 Klara Tenner-Racz,2 Kelledy Manson,3 Michael Wyand,3 Michelle A. Lifton,1 Christie E. Nickerson,1 Tongming Fu,4 John W. Shiver,4 and Norman L. Letvin1

Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 022151; Department of Pathology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany2; Primedica-Mason Laboratories, Worchester, Massachusetts 016083; and Merck Research Laboratories, West Point, Pennsylvania 194864

Received 19 January 2000/Accepted 12 May 2000

The potential contribution of a plasmid DNA construct to vaccine-elicited protective immunity was explored in the simian immunodeficiency virus (SIV)/macaque model of AIDS. Making use of soluble major histocompatibility class I/peptide tetramers and peptide-specific killing assays to monitor CD8+ T-lymphocyte responses to a dominant SIV Gag epitope in genetically selected rhesus monkeys, a codon-optimized SIV gag DNA vaccine construct was shown to elicit a high-frequency SIV-specific cytotoxic T-lymphocyte (CTL) response. This CTL response was demonstrable in both peripheral blood and lymph node lymphocytes. Following an intravenous challenge with the highly pathogenic viral isolate SIVsm E660, these vaccinated monkeys developed a secondary CTL response that arose with more rapid kinetics and reached a higher frequency than did the postchallenge CTL response in control plasmid-vaccinated monkeys. While peak plasma SIV RNA levels were comparable in the experimentally and control-vaccinated monkeys during the period of primary infection, the gag plasmid DNA-vaccinated monkeys demonstrated better containment of viral replication by 50 days following SIV challenge. These findings indicate that a plasmid DNA vaccine can elicit SIV-specific CTL responses in rhesus monkeys, and this vaccine-elicited immunity can facilitate the generation of secondary CTL responses and control of viral replication following a pathogenic SIV challenge. These observations suggest that plasmid DNA may prove a useful component of a human immunodeficiency virus type 1 vaccine.

* Corresponding author. Present address: Wyeth Lederle Vaccines and Pediatrics, Bldg. 180, Rm. 216-37, 401 N. Middletown Rd., Pearl River, NY 10965. Phone: (914) 732-3036. Fax: (914) 732-4941. E-mail: eganm{at}WAR.Wyeth.com.

Journal of Virology, August 2000, p. 7485-7495, Vol. 74, No. 16
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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