Design of highly pure and safe vaccines in post-genomic era unfortunately includes the inherent lack of immunostimulatory properties of proteins and peptides. Vaccine adjuvants are therefore considered key components in modern vaccinology since they provide the necessary help of enhancing the immune responses. Over the past two decades, Dr. Podack's laboratory has developed an exciting and avant-garde reagent: a heat shock protein-based vaccine, chaperone gp96, that generates effective antitumor and anti-infectious immunity in vivo. State-of- the- art secreted gp96-Ig vaccine provides within one molecule strong adjuvant properties and antigen specificity for cross-priming CD8 T cells and activation of innate immunity. Gp96-peptide complexes were identified as an extremely efficient, femto-molar pathway of MHC I-mediated antigen cross-presentation, generating CD8 CTL responses detectable in the blood, spleen, liver, intestinal and reproductive tract lamina propria, and intraepithelial compartment, respectively. These studies provided the first evidence that cell-based gp96-Ig-secreting vaccines may serve as a potent modality to induce not only systemic but also mucosal immunity. The gp96-Ig vaccine strategy has been utilized in clinical trials for non-small cell lung cancer (NSCLC) patients and as prophylactic SIV vaccine to protect nonhuman primates from mucosal infection upon challenge with SIV, demonstrating the feasibility and benefits of this approach for both safety and efficacy.
- Heat shock proteins
ASJC Scopus subject areas
- Immunology and Microbiology(all)
- Biochemistry, Genetics and Molecular Biology(all)