Because HIV infection is most commonly transmitted at mucosal surfaces, anti-HIV mucosal cellular immune responses, including mucosal CTL, are likely to play a significant role in vaccine-induced protection against sexually transmitted HIV infection. However, progress in the development of mucosal HIV vaccines has been hampered by the lack of safe and effective mucosal adjuvants. The overall goal for this project is to identify and evaluate vaccine adjuvants and delivery systems that will be non-toxic and effective for the induction of anti-HIV systemic and mucosal CTL when delivered with candidate HIV vaccines by the intranasal route.
The specific aims of this project are:
Aim 1 : To study the use of select cytokines and mutant cholera toxin (mCT) for their ability to serve as mucosal adjuvants for the induction of systemic and mucosal CTL when delivered intranasally with mixtures of Th-CTL HIV peptides or MVA expressing multiple HIV Th-CTL epitopes.
Aim 2 : To study the use of mucosal vaccine delivery vehicles such as Rhino Vax, lipid cochleates, and Carbopol with intranasally delivered HIV Th-CTL epitope-based vaccines and cytokine adjuvants.
Aim 3 : Evaluate the immunogenicity of combinations of MVA expressing linear arrays of HIV Th-CTL determinants and mixtures of Th-CTL peptides in prime-boost combinations delivered intranasally and/or systematically for their ability to induce anti-HIV Th and CTL responses at mucosal sites.
Aim 4 : To evaluate select cytokine adjuvants and vaccine delivery vehicles in non-human primates for their ability to induce systemic and mucosal CTL after intranasal immunization.
