An evolving strategy for the prevention of sexually transmitted diseases is the development of broad spectrum vaginal microbicides. Many of these microbicides (e.g. detergents like nonoxynol-9) have mechanisms of action that are not limited to specific pathogens and may have deleterious effects on host cells or may compromise epithelial integrity. In contrast, antibodies are naturally occurring microbicides that are highly specific, yet, by working in combination with other antibodies, can achieve broad spectrum protection without injuring healthy tissues or commensal organisms. The specificity of antibodies together with their versatility make them leading microbicide candidates. The objective of this project is to develop antibodies specific for human papillomavirus (HPV-16), a sexually transmitted pathogen associated with cervical cancer, that can be combined with antibodies against other STD pathogens already being produced in corn (plantibodies) by EPIcyte. The first specific aim is to generate a panel of anti-HPV human monoclonal antibodies by immunizing transgenic mice with HPV virus-like particles (VLPs). These human monoclonals will be tested for in vitro neutralization and in vivo efficacy in the second specific aim. The phase II proposal will include production of select anti-HPV human monoclonals in plant, and clinical evaluation of these plantibodies.
Antibody-based technology is now coming to fruition for systemic therapeutics, but the untapped commercial applications for antibodies are in mucosal prevention. A vaginal microbicide is one important application for mucosal antibodies; antibody technology is so flexible that it is readily extended to other reproductive health applications or to the prevention of diseases by pathogens at other mucosal sites. The production of antibodies in plant as plantibodies will enable this technology to meet cost and capacity demands.
