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Mosaic vaccines elicit CD8(+) T lymphocyte responses that confer enhanced immune coverage of diverse HIV strains in monkeys

  1. Author:
    Santra, S.
    Liao, H. X.
    Zhang, R. J.
    Muldoon, M.
    Watson, S.
    Fischer, W.
    Theiler, J.
    Szinger, J.
    Balachandran, H.
    Buzby, A.
    Quinn, D.
    Parks, R. J.
    Tsao, C. Y.
    Carville, A.
    Mansfield, K. G.
    Pavlakis, G. N.
    Felber, B. K.
    Haynes, B. F.
    Korber, B. T.
    Letvin, N. L.

  2. Author Address

    [Santra, Sampa; Balachandran, Harikrishnan; Buzby, Adam; Quinn, David; Letvin, Norman L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Liao, Hua-Xin; Zhang, Ruijin; Parks, Robert J.; Tsao, Chun-Yen; Haynes, Barton F.] Duke Univ, Med Ctr, Durham, NC USA. [Muldoon, Mark] Univ Manchester, Sch Math, Manchester, Lancs, England. [Watson, Sydeaka; Fischer, Will; Theiler, James; Szinger, James; Korber, Bette T.] Los Alamos Natl Lab, Los Alamos, NM USA. [Watson, Sydeaka] Baylor Univ, Dept Stat Sci, Waco, TX 76798 USA. [Carville, Angela; Mansfield, Keith G.] New England Reg Primate Res Ctr, Southborough, MA 01772 USA. [Pavlakis, George N.; Felber, Barbara K.] NCI, NIH, Frederick, MD 21701 USA. [Korber, Bette T.] Santa Fe Inst, Santa Fe, NM 87501 USA.;Letvin, NL, Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.;nletvin@bidmc.harvard.edu
    1. Year: 2010
    2. Date: Mar
  2. Journal: Nature Medicine
    1. 16
    2. 3
    3. Pages: 324-U122
  4. Type of Article: Article
  5. ISSN: 1078-8956
  1. Abstract:

    An effective HIV vaccine must elicit immune responses that recognize genetically diverse viruses(1,2). It must generate CD8(+) T lymphocytes that control HIV replication and CD4(+) T lymphocytes that provide help for the generation and maintenance of both cellular and humoral immune responses against the virus(3-5). Creating immunogens that can elicit cellular immune responses against the genetically varied circulating isolates of HIV presents a key challenge for creating an HIV vaccine(6,7). Polyvalent mosaic immunogens derived by in silico recombination of natural strains of HIV are designed to induce cellular immune responses that recognize genetically diverse circulating virus isolates(8). Here we immunized rhesus monkeys by plasmid DNA prime and recombinant vaccinia virus boost with vaccine constructs expressing either consensus or polyvalent mosaic proteins. As compared to consensus immunogens, the mosaic immunogens elicited CD8(+) T lymphocyte responses to more epitopes of each viral protein than did the consensus immunogens and to more variant sequences of CD8(+) T lymphocyte epitopes. This increased breadth and depth of epitope recognition may contribute both to protection against infection by genetically diverse viruses and to the control of variant viruses that emerge as they mutate away from recognition by cytotoxic T lymphocytes.

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  2. DOI: 10.1038/nm.2108
  3. View record in Web of Science®
  4. WOS: 000275289500039

Library Notes

  1. Fiscal Year: FY2009-2010
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