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Journal of Virology, July 2004, p. 7490-7497, Vol. 78, No. 14
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.14.7490-7497.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Heterologous Envelope Immunogens Contribute to AIDS Vaccine Protection in Rhesus Monkeys

Norman L. Letvin,1,2* Yue Huang,1 Bimal K. Chakrabarti,1 Ling Xu,1 Michael S. Seaman,2 Kristin Beaudry,2 Birgit Korioth-Schmitz,2 Faye Yu,2 Daniela Rohne,2 Kristi L. Martin,2 Ayako Miura,2 Wing-Pui Kong,1 Zhi-Yong Yang,1 Rebecca S. Gelman,3 Olga G. Golubeva,3 David C. Montefiori,4 John R. Mascola,1 and Gary J. Nabel1

Vaccine Research Center, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892-3005,1 Beth Israel Deaconess Medical Center,2 Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215,3 Duke University Medical Center, Durham, North Carolina 277104

Received 21 October 2003/ Accepted 6 March 2004

Because a strategy to elicit broadly neutralizing anti-human immunodeficiency virus type 1 (HIV-1) antibodies has not yet been found, the role of an Env immunogen in HIV-1 vaccine candidates remains undefined. We sought to determine whether an HIV-1 Env immunogen genetically disparate from the Env of the challenge virus can contribute to protective immunity. We vaccinated Indian-origin rhesus monkeys with Gag-Pol-Nef immunogens, alone or in combination with Env immunogens that were either matched or mismatched with the challenge virus. These animals were then challenged with a pathogenic simian-human immunodeficiency virus. The vaccine regimen included a plasmid DNA prime and replication-defective adenoviral vector boost. Vaccine regimens that included the matched or mismatched Env immunogens conferred better protection against CD4+ T-lymphocyte loss than that seen with comparable regimens that did not include Env immunogens. This increment in protective immunity was associated with anamnestic Env-specific cellular immunity that developed in the early days following viral challenge. These data suggest that T-lymphocyte immunity to Env can broaden the protective cellular immune response to HIV despite significant sequence diversity of the strains of the Env immunogens and can contribute to immune protection in this AIDS vaccine model.

* Corresponding author. Mailing address: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215. Phone: (617) 667-2766. Fax: (617) 667-8210. E-mail: nletvin{at}bidmc.harvard.edu.

Journal of Virology, July 2004, p. 7490-7497, Vol. 78, No. 14
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.14.7490-7497.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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