Gp96SIVIg immunization induces potent polyepitope specific, multifunctional memory responses in rectal and vaginal mucosa

Natasa Strbo, Monica Vaccari, Savita Pahwa, Michael A. Kolber, Eva Fisher, Louis Gonzalez, Melvin N. Doster, Anna Hryniewicz, Barbara K. Felber, George N. Pavlakis, Genoveffa Franchini, Eckhard R Podack

Research output: Contribution to journalArticle

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2619-2625
Number of pages7
JournalVaccine
Volume29
Issue number14
DOIs
StatePublished - Mar 21 2011

Keywords

  • Gp96-chaperone
  • Mucosa
  • Non-human primate
  • Rectum
  • Vagina

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

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    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. (2011). Gp96SIVIg immunization induces potent polyepitope specific, multifunctional memory responses in rectal and vaginal mucosa. Vaccine, 29(14), 2619-2625. https://doi.org/10.1016/j.vaccine.2011.01.044