Plant Based Microbicides and Vaccines to Prevent STIs

基于抗体的杀微生物剂和粘膜疫苗具有共同的拍卖机制，即免疫排除病原体、共同的监管和临床试验考虑以及与低成本/大容量生物制药市场需求相关的生产挑战。转基因植物可以为生产亚基粘膜疫苗和基于抗体的杀微生物剂提供一种经济的替代发酵系统。人类研究表明，植物中产生的疫苗抗原可以刺激血清和粘膜分泌物中抗原特异性抗体的产生，植物中表达的抗体在粘膜激发模型中显示出保护作用。远程

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.