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Gp96(SIV)Ig immunization induces potent polyepitope specific, multifunctional memory responses in rectal and vaginal mucosa

  1. Author:
    Strbo, N.
    Vaccari, M.
    Pahwa, S.
    Kolber, M. A.
    Fisher, E.
    Gonzalez, L.
    Doster, M. N.
    Hryniewicz, A.
    Felber, B. K.
    Pavlakis, G. N.
    Franchini, G.
    Podack, E. R.
  2. Author Address

    [Strbo, Natasa; Pahwa, Savita; Fisher, Eva; Gonzalez, Louis; Podack, Eckhard R.] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA. [Strbo, Natasa; Pahwa, Savita; Kolber, Michael A.; Gonzalez, Louis; Podack, Eckhard R.] Univ Miami, Miller Sch Med, Ctr AIDS Res, Miami, FL 33136 USA. [Vaccari, Monica; Doster, Melvin N.; Hryniewicz, Anna; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, NIH, Bethesda, MD 20892 USA. [Kolber, Michael A.] Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA. [Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Frederick, MD 21702 USA. [Pavlakis, George N.] NCI, Human Retrovirus Sect, Frederick, MD 21702 USA.;Podack, ER, 1600 NW 10th Ave,RMSB 3045, Miami, FL 33136 USA.;epodack@med.miami.edu
    1. Year: 2011
    2. Date: Mar
  1. Journal: Vaccine
    1. 29
    2. 14
    3. Pages: 2619-2625
  2. Type of Article: Article
  3. ISSN: 0264-410X
  1. Abstract:

    The ER-resident chaperone gp96, when released by cell lysis, induces an immunogenic chemokine signature and causes innate immune activation of DC and NK cells. Here we show that intraperitoneal immunization with a genetically engineered, secreted form of gp96, gp96-Ig chaperoning SIV antigens, induces high levels of antigen specific CD8 CTL in the rectal and vaginal mucosa of Rhesus macaques. The frequency of SIV Gag- and SIV Tat-tetramer positive CD8 CTL in the intestinal mucosa reached 30-50% after the third immunization. Tetramer positive CD8 CTL expressed appropriate functional (granzyme B) and migration markers (CD103). The polyepitope specificity of the mucosal CD8 and CD4 response is evident from a strong, multifunctional cytokine response upon stimulation with peptides covering the gag, tat and env proteins. Induction of powerful mucosal effector CD8 CTL, responses by cell-based gp96(SIV)-Ig immunization may provide a pathway to the development of safe and effective SIV/HIV vaccines. (C) 2011 Elsevier Ltd. All rights reserved.

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External Sources

  1. DOI: 10.1016/j.vaccine.2011.01.044
  2. WOS: 000289140600017

Library Notes

  1. Fiscal Year: FY2010-2011
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