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Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid

  1. Author:
    Boyer, J. D.
    Robinson, T. M.
    Kutzler, M. A.
    Vansant, G.
    Hokey, D. A.
    Kumar, S.
    Parkinson, R.
    Wu, L.
    Sidhu, M. K.
    Pavlakis, G. N.
    Felber, B. K.
    Brown, C.
    Silvera, P.
    Lewis, M. G.
    Monforte, J.
    Waldmann, T. A.
    Eldridge, J.
    Weiner, D. B.

  2. Author Address

    NCI, Metab Branch, Frederick, MD 21702 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Althea Technol Inc, Genomix, San Diego, CA 92121 USA. Wyeth, Vaccine Discovery, Pearl River, NY 10965 USA. NCI, Vaccine Branch, Frederick, MD 21702 USA. NIAID, Viral Pathogenesis & Vaccine Branch, Mol Microbiol Lab, Bethesda, MD 20892 USA. So Res Inst, Div Life Sci, Frederick, MD 21701 USA. Bioqual, Res Sect, Rockville, MD 20850 USA.;Waldmann, TA, NCI, Metab Branch, Bldg 10,Room 4N115, Frederick, MD 21702 USA.;tawald@helix.nih.gov dbweiner@mail.med.upenn.edu
    1. Year: 2007
    2. Date: Nov
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 104
    2. 47
    3. Pages: 18648-18653
  4. Type of Article: Article
  5. ISSN: 0027-8424
  1. Abstract:

    The cell-mediated immune profile induced by a recombinant DNA vaccine was assessed in the simian/HIV (SHIV) and macaque model. The vaccine strategy included coimmunization of a DNA-based vaccine alone or in combination with an optimized plasmid encoding macaque IL-15 (pmacIL-15). We observed strong induction of vaccine-specific IFN-gamma-producing CD8(+) and CD4(+) effector T cells in the vaccination groups. Animals were subsequently challenged with 89.6p. The vaccine groups were protected from ongoing infection, and the IL-15 covaccinated group showed a more rapidly controlled infection than the group treated with DNA vaccine alone. Lymphocytes isolated from the group covaccinated with pmacIL-15 had higher cellular proliferative responses than lymphocytes isolated from the macaques that received SHIV DNA alone. Vaccine antigen activation of lymphocytes was also studied for a series of immunological molecules. Although mRNA for IFN-gamma was up-regulated after antigen stimulation, the inflammatory molecules IL-8 and MMP-9 were down-regulated. These observed immune profiles are potentially reflective of the ability of the different groups to control SHIV replication. This study demonstrates that an optimized IL-15 immune adjuvant delivered with a DNA vaccine can impact the cellular immune profile in nonhuman primates and lead to enhanced suppression of viral replication.

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External Sources

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  2. DOI: 10.1073/pnas.0709198104
  3. View record in Web of Science®
  4. WOS: 000251292500055

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