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Journal of Virology, March 2001, p. 2462-2467, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2462-2467.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Elicitation of High-Frequency Cytotoxic T-Lymphocyte Responses against both Dominant and Subdominant Simian-Human Immunodeficiency Virus Epitopes by DNA Vaccination of Rhesus Monkeys

Dan H. Barouch,1,* Abie Craiu,1 Sampa Santra,1 Michael A. Egan,1 Jörn E. Schmitz,1 Marcelo J. Kuroda,1 Tong-Ming Fu,2 Jae-Hwan Nam,3 Linda S. Wyatt,3 Michelle A. Lifton,1 Georgia R. Krivulka,1 Christine E. Nickerson,1 Carol I. Lord,1 Bernard Moss,3 Mark G. Lewis,4 Vanessa M. Hirsch,5 John W. Shiver,2 and Norman L. Letvin1

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 022151; Merck Research Laboratories, West Point, Pennsylvania 194862; Laboratory of Viral Diseases3 and Laboratory of Molecular Microbiology,5 National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20852; and Southern Research Institute, Frederick, Maryland 217014

Received 12 September 2000/Accepted 1 December 2000

Increasing evidence suggests that the generation of cytotoxic T-lymphocyte (CTL) responses specific for a diversity of viral epitopes will be needed for an effective human immunodeficiency virus type 1 (HIV-1) vaccine. Here, we determine the frequencies of CTL responses specific for the simian immunodeficiency virus Gag p11C and HIV-1 Env p41A epitopes in simian-human immunodeficiency virus (SHIV)-infected and vaccinated rhesus monkeys. The p11C-specific CTL response was high frequency and dominant and the p41A-specific CTL response was low frequency and subdominant in both SHIV-infected monkeys and in monkeys vaccinated with recombinant modified vaccinia virus Ankara vectors expressing these viral antigens. Interestingly, we found that plasmid DNA vaccination led to high-frequency CTL responses specific for both of these epitopes. These data demonstrate that plasmid DNA may be useful in eliciting a broad CTL response against multiple epitopes.

* Corresponding Author. Mailing address: 330 Brookline Ave., Research East Room 113, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215. Phone: (617) 667-2042. Fax: (617) 667-8210. E-mail: dan_barouch{at}hotmail.com.

Journal of Virology, March 2001, p. 2462-2467, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2462-2467.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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