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Journal of Virology, May 2001, p. 4430-4434, Vol. 75, No. 9
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.9.4430-4434.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Rabies Virus-Based Vectors Expressing Human Immunodeficiency Virus Type 1 (HIV-1) Envelope Protein Induce a Strong, Cross-Reactive Cytotoxic T-Lymphocyte Response against Envelope Proteins from Different HIV-1 Isolates

James P. McGettigan,1,2 Heather D. Foley,1,2 Igor M. Belyakov,3 Jay A. Berzofsky,3 Roger J. Pomerantz,1,4,5 and Matthias J. Schnell1,4,*

The Dorrance H. Hamilton Laboratories, Center for Human Virology,1 and Departments of Biochemistry and Molecular Pharmacology,4 Microbiology and Immunology,2 and Medicine,5 Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, and Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, Bethesda, Maryland 208923

Received 22 November 2000/Accepted 26 January 2001

Novel viral vectors that are able to induce both strong and long-lasting immune responses may be required as effective vaccines for human immunodeficiency virus type 1 (HIV-1) infection. Our previous experiments with a replication-competent vaccine strain-based rabies virus (RV) expressing HIV-1 envelope protein from a laboratory-adapted HIV-1 strain (NL4-3) and a primary HIV-1 isolate (89.6) showed that RV-based vectors are excellent for B-cell priming. Here we report that cytotoxic T-lymphocyte (CTL) responses against HIV-1 gp160 are induced by recombinant RVs. Our results indicated that a single inoculation of mice with an RV expressing HIV-1 gp160 induced a solid and long-lasting memory CTL response specific for HIV-1 envelope protein. Moreover, CTLs from immunized mice were not restricted to the homologous HIV-1 envelope protein and were able to cross-kill target cells expressing HIV-1 gp160 from heterologous HIV-1 strains. These studies further suggest promise for RV-based vectors to elicit a persistent immune response against HIV-1 and their potential utility as efficacious anti-HIV-1 vaccines.

* Corresponding author. Mailing address: 1020 Locust Street, Suite 335, Philadelphia, PA 19107-6799. Phone: (215) 503-1260. Fax: (215) 923-1956. E-mail: matthias.schnell{at}mail.tju.edu.

Journal of Virology, May 2001, p. 4430-4434, Vol. 75, No. 9
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.9.4430-4434.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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