Heterologous envelope immunogens contribute to AIDS vaccine protection in rhesus monkeys

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7490-7497
Number of pages8
JournalJournal of Virology
Volume78
Issue number14
DOIs
StatePublished - Jul 2004
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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  • Cite this

    Letvin, N. L., Huang, Y., Chakrabarti, B. K., Xu, L., Seaman, M. S., Beaudry, K., Korioth-Schmitz, B., Yu, F., Rohne, D., Martin, K. L., Miura, A., Kong, W. P., Yang, Z. Y., Gelman, R. S., Golubeva, O. G., Montefiori, D. C., Mascola, J. R., & Nabel, G. J. (2004). Heterologous envelope immunogens contribute to AIDS vaccine protection in rhesus monkeys. Journal of Virology, 78(14), 7490-7497. https://doi.org/10.1128/JVI.78.14.7490-7497.2004