INDUCTION OF ANTI-HPV CTL WITH PEPTIDE-CPG DNA CONJUGATE

DESCRIPTION (provided by applicant): The goal of this research program is to produce peptide-immunostimulatory (ISS) DNA conjugates that can stimulate robust anti-papillomavirus Th1 and CTL responses. Successful peptide-ISS conjugates could be used alone or in combination with other papilloma antigens to produce a vaccine for the prevention or treatment of human papillomavirus infection. In the Phase I program, chemical conjugates will be made of peptides encompassing helper T cell and cytotoxic T cell (CTL) epitopes of the HPV oncoprotein E7 and immunostimulatory DNA sequences (ISS) known to stimulate strong Th1 and CTL responses. The ability of these peptide-ISS conjugates to induce Th1 and cytotoxic T cell responses will be tested in mice. The E7 peptide-ISS conjugates will also be co-injected with the HPV capsid protein L1 to determine the ability of E7-peptide conjugates to influence the quality and magnitude antibody and T cell responses to the capsid protein. If Phase I results prove this approach is feasible, Phase II studies will involve preparation of peptide-ISS conjugates encompassing significant portions of HPV E7 and/or E6, testing those conjugates for induction of immune responses when injected singly and together with other HPV antigens, and preparation of peptide-ISS conjugate formulations that could be used in human clinical trials.