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 language | English (US) |
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Pages (from-to) | 2619-2625 |
Number of pages | 7 |
Journal | Vaccine |
Volume | 29 |
Issue number | 14 |
DOIs | |
State | Published - 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