The applicants propose to test the hypothesis that a fusion protein made between a fragment of gp160 and the L1 capsid protein of human papilloma virus (HPV) will form a chimeric viral like particle (CVLP) that will be useful as a new delivery system for mucosal immunization against HIV-1. This hypothesis will be tested by fusing a segment of gp160 that harbors HLA-0201 restricted epitopes with L1 to produce a HIVgp160CVLP. This chimera will be used as the principal immunogen in HLA-0201 transgenic mice to induce mucosal and systemic CTL responses specific for these epitopes. There are 3 specific aims: 1) to determine whether immunization with HIVgp160CVLP will induce HIV-specific mucosal and systemic responses via the subcutaneous, intranasal, or intrarectal routes; 2) to determine whether CVLP that contains enriched HLA-A0201 epitopes can induce CTL responses to these epitopes; and 3) and to determine the ability of adjuvants (Cholera toxin (CT) and IL-12) to enhance a mucosal response.
Shi, W; Liu, J; Huang, Y et al. (2001) Papillomavirus pseudovirus: a novel vaccine to induce mucosal and systemic cytotoxic T-lymphocyte responses. J Virol 75:10139-48 |