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，即对病原体的免疫排斥，共同的监管和临床试验考虑，以及与低成本/大容量市场对生物制药的需求相关的生产挑战。转基因植物可以提供一种经济的替代发酵系统来生产亚单位粘膜疫苗和基于抗体的杀微生物剂。对人类的研究表明，在植物中生产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黏膜攻击模型中显示出保护作用。长距离的 目的是开发安全有效的植物制成的杀微生物剂和粘膜疫苗，以防止经阴道传播。我们假设，足够浓度的粘膜抗体，无论是被动注射还是主动诱导，都可以排除性传播病原体在阴道内，从而防止传播。该项目的目标是：(A)评估主动免疫策略，以使阴道免疫球蛋白和S-免疫球蛋白A比活性提高数倍和/或100%中和100TCID50病原体；(B)确定局部应用植物抗体100%中和单纯疱疹病毒和艾滋病毒的100TCID50所需的粘膜抗体浓度。虽然中和活性和局部特异性抗体浓度是替代的保护措施，但这些信息(与动物的主动和被动免疫研究相结合)将促进将在人类疗效试验中成功的产品的开发。具体目的是：(1)比较口服和阴道内注射植物来源的乙肝表面抗原的安全性和特异性阴道免疫反应。 该项目的目的是：(1)检测以前接种过疫苗的妇女的安全性和特异性阴道免疫应答(以中和抗体活性、特异性Ig G、Ig A和S-Ig A来衡量)；(3)测定口服和经阴道接种植物源性艾滋病毒疫苗的安全性和特异性阴道免疫应答；(3)测定经粘膜接种的HSV/HIV植物抗体的安全性和时效依赖性；(4)评价植物源HBs Ag/HPV或CTB-PI/HSV融合蛋白在妇女中的安全性和免疫原性。

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.