Research Project
3548028
Several experiments subunit vaccines based on recombinant HIV-1 gp160 have been developed for HIV-1 and tested in human volunteers. Specific antibody responses and antigen-specific proliferative responses were induced. However, multiple immunizations containing relatively large amounts of recombinant HIV-1 gp160 were needed suggesting that these vaccines were only weakly immunogenic. We have developed methods to purify saponins from Quillaja saponaria and have identified one, termed QS-21, that is a potent adjuvant. The adjuvant activity includes the ability to augment antibody responses, including isotype switching and increases in total titers. The QS-21 also augments cell-mediated immune responses including the induction of class-I MHC antigen restricted cytotoxic T-lymphocytes (CTL). Our proposed research program is designed to characterize and further evaluate the QS-21 adjuvant for use with recombinant HIV-1 proteins and synthetic peptides. Experimental vaccine formulations containing QS-21 conjugated directly to protein immunogens will be prepared and tested in mice and guinea pigs using both parenteral and oral delivery routes to broadly evaluate immunogenicity and ability to induce mucosal immunity. Similar vaccine formulations will be prepared using carriers, specifically liposomes and biodegradable polymers. Again, these will be tested using parenteral and oral routes of administration to evaluate the effects of slow-release delivery on immune responses and on the induction of mucosal immunity. The goal is to develop one or more experimental HIV-1 subunit vaccine formulation, containing the QS-21 adjuvant, that can induce potent humoral and cell-mediated immune responses specific for HIV-1 gp120.
