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SIVmac239 MVA vaccine with and without a DNA prime, similar prevention of infection by a repeated dose SIVsmE660 challenge despite different immune responses

  1. Author:
    Lai, L. L.
    Kwa, S. F.
    Kozlowski, P. A.
    Montefiori, D. C.
    Nolen, T. L.
    Hudgens, M. G.
    Johnson, W. E.
    Ferrari, G.
    Hirsch, V. M.
    Felber, B. K.
    Pavlakis, G. N.
    Earl, P. L.
    Moss, B.
    Amara, R. R.
    Robinson, H. L.

  2. Author Address

    [Robinson, Harriet L.] GeoVax Inc, Smyrna, GA 30080 USA. [Lai, Lilin; Kwa, Sue-Fen; Amara, Rama Rao] Emory Univ, Div Microbiol & Immunol, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. [Kozlowski, Pamela A.] Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol Immunol & Parasitol, New Orleans, LA 70112 USA. [Kozlowski, Pamela A.; Ferrari, Guido] Duke Univ, Med Ctr, Dept Surg, Lab AIDS Vaccine Res & Dev, Durham, NC 27710 USA. [Nolen, Tracy L.; Hudgens, Michael G.] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. [Johnson, Welkin E.] Harvard Univ, New England Natl Primate Res Ctr, Southborough, MA 01772 USA. [Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Frederick, MD 21702 USA. [Pavlakis, George N.] NCI, Human Retrovirus Sect, Vaccine Branch, Frederick, MD 21702 USA. [Earl, Patricia L.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Amara, Rama Rao] Emory Univ, Vaccine Res Ctr, Atlanta, GA 30329 USA. [Amara, Rama Rao] Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30329 USA.;Robinson, HL (reprint author), GeoVax Inc, Smyrna, GA 30080 USA;hrobinson@geovax.com
    1. Year: 2012
    2. Date: Feb
  2. Journal: Vaccine
    1. 30
    2. 9
    3. Pages: 1737-1745
  4. Type of Article: Article
  5. ISSN: 0264-410X
  1. Abstract:

    Background: Vaccine regimens using different agents for priming and boosting have become popular for enhancing T cell and Ab responses elicited by candidate HIV/AIDS vaccines. Here we use a simian model to evaluate immunogenicity and protective efficacy of a recombinant modified vaccinia Ankara (MVA) vaccine in the presence and absence of a recombinant DNA prime. The simian vaccines and regimens represent prototypes for candidate HIV vaccines currently undergoing clinical testing. Method: Recombinant DNA and MVA immunogens expressed simian immunodeficiency virus (SIV)mac239 Gag, PR, RT. and Env sequences. Vaccine schedules tested inoculations of MVA at months 0, 2, and 6 (MMM regimen) or priming with DNA at months 0 and 2 and boosting with MVA at months 4 and 6 (DDMM regimen). Twelve weekly rectal challenges with the heterologous Sly smE660 were initiated at 6 months following the last immunization. Results: Both regimens elicited similar 61-64% reductions in the per challenge risk of SIVsmE660 transmission despite raising different patterns of immune responses. The DDMM regimen elicited higher magnitudes of CD4 T cells whereas the MMM regimen elicited higher titers and greater avidity Env-specific IgG and more frequent and higher titer SIV-specific IgA in rectal secretions. Both regimens elicited similar magnitudes of CD8 T cells. Magnitudes of T cell responses, specific activities of rectal IgA Ab, and the tested specificities for neutralization and antibody-dependent cellular cytotoxicity did not correlate with risk of infection. However, the avidity of Env-specific IgG had a strong correlation with the per challenge risk of acquisition, but only for the DDMM group. Conclusions: We conclude that for the tested immunogens in rhesus macaques, the simpler MMM regimen is as protective as the more complex DDMM regimen. (C) 2011 Elsevier Ltd. All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.vaccine.2011.12.026
  3. View record in Web of Science®
  4. WOS: 000301558200024

Library Notes

  1. Fiscal Year: FY2011-2012
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