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Enhancement of primary and secondary cellular immune responses against human immunodeficiency virus type 1 Gag by using DNA expression vectors that target Gag antigen to the secretory pathway

  1. Author:
    Qiu, J. T.
    Liu, B. D.
    Tian, C. J.
    Pavlakis, G. N.
    Yu, X. F.

  2. Author Address

    Yu XF Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol 615 N Wolfe St Baltimore, MD 21205 USA Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol Baltimore, MD 21205 USA NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program Frederick, MD 21702 USA
    1. Year: 2000
  2. Journal: Journal of Virology
    1. 74
    2. 13
    3. Pages: 5997-6005
  4. Type of Article: Article
  1. Abstract:

    In this study, we have investigated the influence of antigen targeting after DNA vaccination upon the induction of cellular immune responses against human immunodeficiency virus type 1 (HIV-1) Gag. In addition to the standard version of HIV-1 Gag, we constructed Gag expression vectors that encode a secreted (Sc-Gag) and a cytoplasmic (Cy-Gag) Gag molecule. Although all three HIV-1 Gag expression vectors induced detectable humoral and cellular immune responses, after intramuscular injection the DNA vector encoding the Sc-Gag generated the highest primary cytotoxic T-lymphocyte (CTL) and T-helper responses. Mice immunized with one of the HIV-1 Gag DNA vectors (but not with the control vector pcDNA3.1) developed a protective immune response against infection with recombinant vaccinia virus expressing HIV-1 Gag, and this response persisted for 125 days. The magnitude of the protection correlated with the levels of Gag-specific ex vivo CTL activity and the number of CD8(+) T cells producing gamma interferon. The DNA vector encoding the Sc-Gag induced higher levels of protection and greater secondary CTL responses than did the DNA vector encoding Cy-Gag. [References: 42]

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