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Journal of Virology, March 2002, p. 2730-2738, Vol. 76, No. 6
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.6.2730-2738.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

High-Level Primary CD8+ T-Cell Response to Human Immunodeficiency Virus Type 1 Gag and Env Generated by Vaccination with Recombinant Vesicular Stomatitis Viruses

Karl Haglund,1,2 Ingrid Leiner,3,4,{dagger} Kristen Kerksiek,4,{ddagger} Linda Buonocore,1 Eric Pamer,3,4,{dagger} and John K. Rose1,5*

Departments of Pathology,1 Cell Biology,5 Medicine,3 Program in Microbiology,2 Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 065104

Received 26 October 2001/ Accepted 22 December 2001

We investigated the primary cellular immune responses to human immunodeficiency virus type 1 (HIV-1) Env and Gag proteins elicited by recombinant vesicular stomatitis viruses (rVSVs). The primary response to Env peaked 5 to 7 days after intraperitoneal vaccination, at which time 40% of CD8+ cells were Env tetramer positive and activated (CD62LLo). These freshly isolated cells actively lysed target cells pulsed with the p18-I10 peptide and secreted gamma interferon and tumor necrosis factor alpha after stimulation with the Env p18-I10 peptide. The primary response to Env elicited by rVSVs was sixfold higher than that elicited by recombinant vaccinia viruses (rVVs) at 5 days postvaccination. An intranasal route of vaccination with VSV-Env also elicited a strong primary response to Env. The primary immune response to Gag elicited by rVSV peaked 7 days after vaccination, at which time 3% of CD8+ cells were Gag tetramer positive and CD62LLo and functional by intracellular cytokine staining. This response was eightfold higher than that elicited by rVV expressing Gag. VSV-GagEnv, which expresses both Gag and Env from a single recombinant, also induced strong cytotoxic T-lymphocyte (CTL) responses to both Env and Gag. Our quantitative analyses illustrate the potency of the VSV vector system in CTL induction.

* Corresponding author. Mailing address: Departments of Pathology and Cell Biology, Yale University School of Medicine, New Haven, CT 06510. Phone: (203) 785-6794. Fax: (203) 785-7467. E-mail: jrose{at}biomed.med.yale.edu.

{dagger} Present address: Infectious Diseases Service, Laboratory of Antimicrobial Immunity, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.

{ddagger} Present address: LMU München, Institut für Immunologie, 803360 Munich, Germany.

Journal of Virology, March 2002, p. 2730-2738, Vol. 76, No. 6
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.6.2730-2738.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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Copyright © 2002 by the American Society for Microbiology. All rights reserved.