Cytokine profiles in seronegative volunteers immunized with a recombinant canarypox and gp120 prime-boost HIV-1 vaccine

Steffanie Sabbaj, Mark J. Mulligan, Ray Hahn Hsieh, Robert B. Belshe, Jerry R. McGhee, D. Schwartz, D. Burke, Geoffrey J. Gorse, Sharon Frey, Jiri Mestecky, Susan Jackson, John W. Gnann, Paul A. Goepfert, Raphael Dolin, Michael C. Keefer, Thomas G. Evans, M. Julianna McElrath, Lawrence Corey, Barney S. Graham, Peter WrightPaul Spearman, Thomas Matthews, David Montefiori, Kent Weinhold, Dani Bolognesi, Mary Allen, Barbara Savarese

Research output: Contribution to journalArticle

Abstract

Objectives: To study memory T cell proliferative responses and cytokine profiles induced in HIV-1 seronegative volunteers immunized with a live recombinant canarypox vector expressing HIV-1 antigens (ALVAC-HIV) and boosted with a recombinant gp120 subunit vaccine. Design: HIV-specific T cell proliferative responses and cytokines were measured 2 weeks after vaccination. Cytokines secreted by T helper 1 cells (Th1) [interleukin (IL)-2 and interferon-γ (IFN-γ)] and T helper 2 (Th2) cells (IL-4, IL-5, IL-6, and IL-10) were assessed both at the mRNA and the protein level. Methods: Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with HIV antigens. Subsequently, T cell proliferation was measured in a standard lymphoproliferation assay; secreted cytokines were measured using an enzyme-linked immunosorbent assay and upregulation of cytokine mRNA was measured using reverse transcriptase polymerase chain reaction. Results: All individuals who had received ALVAC-HIV followed by the protein vaccine exhibited HIV-1-specific T cell proliferative responses. Moreover, the PBMC of all prime-boost vaccinated individuals produced detectable IFN-γ and IL-10 in response to stimulation with HIV-1 envelope glycoprotein antigens; 83% also had detectable levels of IL-2 and IL-6, 71% had detectable levels of IL-4, and 86% had detectable levels of IL-5. Conclusions: These data indicate that this vaccination regimen was inducing both Th1- and Th2-type responses to HIV-1 envelope antigens. This prime-boost vaccination approach elicited T cell help for the generation of cytotoxic T lymphocyte responses as well as help for antibody production and so promises to generate a broad HIV-1-specific immune response. (C) 2000 Lippincott Williams and Wilkins.

Original languageEnglish (US)
Pages (from-to)1365-1374
Number of pages10
JournalAIDS
Volume14
Issue number10
DOIs
StatePublished - Jul 28 2000

Keywords

  • Cellular immunity
  • Cytokines
  • T helper lymphocytes
  • Th1/Th2
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Sabbaj, S., Mulligan, M. J., Hsieh, R. H., Belshe, R. B., McGhee, J. R., Schwartz, D., Burke, D., Gorse, G. J., Frey, S., Mestecky, J., Jackson, S., Gnann, J. W., Goepfert, P. A., Dolin, R., Keefer, M. C., Evans, T. G., McElrath, M. J., Corey, L., Graham, B. S., ... Savarese, B. (2000). Cytokine profiles in seronegative volunteers immunized with a recombinant canarypox and gp120 prime-boost HIV-1 vaccine. AIDS, 14(10), 1365-1374. https://doi.org/10.1097/00002030-200007070-00009