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Design and in vivo immunogenicity of a polyvalent vaccine based on SIVmac regulatory genes

  1. Author:
    Hel, Z.
    Tryniszewska, E.
    Tsai, W. P.
    Johnson, J. M.
    Harrod, R.
    Fullen, J.
    Kalyanaraman, V. S.
    Altman, J. D.
    McNally, J.
    Karpova, T.
    Felber, B. K.
    Tartaglia, J.
    Franchini, G.
  2. Author Address

    NCI, Basic Res Lab, 41-D804, Bethesda, MD 20892 USA NCI, Basic Res Lab, Bethesda, MD 20892 USA Med Acad Bialystok, Dept Paediat 3, Bialystok, Poland Adv BioSci Labs Inc, Kensington, MD USA Emory Univ, Yerkes Reg Primate Res Ctr, Vaccine Ctr, Atlanta, GA 30322 USA NCI, Fluorescence Imaging Facil, Bethesda, MD 20892 USA NCI, Human Retrovirus Pathogenesis Sect, Frederick, MD 21701 USA Aventis Pasteur, Toronto, ON, Canada Franchini G NCI, Basic Res Lab, 41-D804, Bethesda, MD 20892 USA
    1. Year: 2002
  1. Journal: DNA and Cell Biology
    1. 21
    2. 9
    3. Pages: 619-626
  2. Type of Article: Article
  1. Abstract:

    Most vaccine modalities for human immunodeficiency virus type 1 (HIV-1) tested for immunogenicity and efficacy in the SIVmac (simian immunodeficiency virus) macaque model do not include the viral regulatory proteins. Because viral regulatory proteins are expressed early during the virus life cycle and represent an additional source of antigens, their inclusion as a vaccine component may increase the overall virus-specific immune response in vaccinees. However, at least two of the early proteins, Tat and Nef, may be immunosuppressive, limiting their usefulness as components of an SIV vaccine. We have constructed a polyvalent chimeric protein in which the open reading frames for Tat and Nef have been reassorted and the nuclear localization sequence for Tat and Rev and the myristoylation site for Nef have been removed. The resulting DNA plasmid (pDNA-SIV-Retanef) (pDNA-SIV-RTN) encodes a protein of 55 kDa (Retanef) that localizes at the steady state in the cytoplasma of transfected cells. Both the DNA-SIV-RTN and the highly attenuated recombinant poxvirus vector NYVAC-SIV-RTN were demonstrated to be immunogenic in SIVmac251-infected macaques treated with ART as well as in naive macaques. An equivalent strategy may be used for the generation of polyvalent antigens encoding the regulatory proteins in a HIV-1 vaccine candidate.

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