Antibody-based microbicides and mucosal vaccines share a common mechanism of auction, i.e. immune exclusion of pathogens, common regulatory and clinical trial considerations, and production challenges associated with low cost/large capacity market demands for biopharmaceuticals. Transgenic plants could provide an economic alternative to fermentation systems for the production of subunit mucosal vaccines and antibody-based microbicides. Studies in humans have demonstrated that vaccine antigens produced in plants can stimulate production of antigen-specific antibodies in serum and mucosal secretions and antibodies expressed in plants have shown protection in a mucosal challenge model. The Long-Range Objective is to develop safe and effective plant-made microbicides and mucosal vaccines that prevent transmission in the vagina. We Hypothesize that sufficient concentrations of mucosal antibodies, either passively administered or actively elicited, can exclude sexually transmitted pathogens in the vagina, resulting in prevention of transmission. Goals of the Project are: (a) to evaluate active immunization strategies for multi-fold increases in specific activity of vaginal IgG and S-IgA and/or 100% neutralization of 100 TCID50 of pathogen; (b) to determine the mucosal antibody concentrations required for 100% neutralization of 100 TCID50 of HSV and HIV by topically applied plantibodies. Although neutralization activity and local specific antibody concentrations are surrogate measures of protection, this information (when coupled with active and passive immunization studies in animals) will enhance the development of products that will be successful in human efficacy trials.
Specific aims are: (1) to compare the safety and specific vaginal immune responses to plant-derived HBsAg administered orally and intravaginally in previously vaccinated women; (2) to determine in women the safety and specific vaginal immune responses (as measured by neutralizing antibody activity, specific IgG, IgA, and S-IgA) to orally and vaginally administered, plant-derived CTB-P1, a mucosal HIV vaccine; (3) to determine in women the safety and timedependent neutralizing activity of mucosally applied HSV/HIV plantibodies; (4) to evaluate in women the safety and immunogenicity of either plant-derived HBsAg/HPV or CTB-PI/HSV fusion proteins.
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