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Improved vaccine protection from simian AIDS by the addition of nonstructural simian immunodeficiency virus genes

  1. Author:
    Hel, Z.
    Tsai, W. P.
    Tryniszewska, E.
    Nacsa, J.
    Markham, P. D.
    Lewis, M. G.
    Pavlakis, G. N.
    Felber, B. K.
    Tartaglia, J.
    Franchini, G.

  2. Author Address

    NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. Univ Alabama, Dept Pathol, Ctr AIDS Res, Birmingham, AL 35249 USA. Med Univ Bialystok, Dept Pediat 3, Waszyngtona, Poland. Adv BioSci Labs, Kensington, MD 20895 USA. Bioqual, Rockville, MD 20850 USA. NCI, Human Retrovirus Sect, Frederick, MD 21702 USA. NCI, Human Retrovirus Pathogenesis Sect, Frederick, MD 21702 USA. Sanofi Pasteur, Toronto, ON, Canada.;Franchini, G, NCI, Anim Models & Retroviral Vaccines Sect, 41-D804, Bethesda, MD 20892 USA.;franchig@mail.nih.gov
    1. Year: 2006
    2. Date: Jan
  2. Journal: Journal of Immunology
    1. 176
    2. 1
    3. Pages: 85-96
  4. Type of Article: Article
  5. ISSN: 0022-1767
  1. Abstract:

    An HIV-1 vaccine able to induce broad CD4(+) and CD8(+) T cell responses may provide long-term control of viral replication. In this study we directly assess the relative benefit of immunization with vaccines expressing three structural Ags (Gag, Pol, and Env), three early regulatory proteins (Rev, Tat, and Nef), or a complex vaccine expressing all six Ags. The simultaneous administration of all six Ags during vaccination resulted in Ag competition manifested by a relative reduction of CD8(+) T cell and lymphoproliferative responses to individual Ags. Despite the Ag competition, vaccination with all six Ags resulted in a delay in the onset and a decrease in the extent of acute viremia after mucosal challenge exposure to highly pathogenic SIVmac251. Reduced levels of acute viremia correlated with lower post-set point viremia and long-term control of infection. In immunized animals, virus-specific CD4(+) T cell and lymphoproliferative responses were preserved during acute viremia, and the maintenance of these responses predicted the long-term virological outcome. Taken together, these results suggest that the breadth of the immune response is probably more important than high frequency responses to a limited number of epitopes. These data provide the first clear evidence of the importance of nonstructural HIV Ags as components of an HIV-1 vaccine.

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External Sources

  1. View record in Web of Science®
  2. WOS: 000234262600013

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