Gp96 SIV Ig immunization induces potent polyepitope specific, multifunctional memory responses in rectal and vaginal mucosa |
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Authors: | Strbo Natasa Vaccari Monica Pahwa Savita Kolber Michael A Fisher Eva Gonzalez Louis Doster Melvin N Hryniewicz Anna Felber Barbara K Pavlakis George N Franchini Genoveffa Podack Eckhard R |
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Institution: | a Department of Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, FL 33136, United States b Center for AIDS Research University of Miami, Miller School of Medicine, Miami, FL 33136, United States c Animal Models and Retroviral Vaccines Section, National Cancer Institute, NIH, Bethesda, MD 20892, United States d Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL 33136, United States e Human Retrovirus Pathogenesis Section, National Cancer Institute-Frederick, Frederick, MD 21702, United States f Human Retrovirus Section, National Cancer Institute-Frederick, Frederick, MD 21702, United States |
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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 gp96SIV-Ig immunization may provide a pathway to the development of safe and effective SIV/HIV vaccines. |
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Keywords: | gp96-chaperone Mucosa Non-human primate Rectum Vagina |
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