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，即病原体的免疫排斥、共同的监管和临床试验考虑以及与生物药品的低成本/大容量市场需求相关的生产挑战。转基因植物可以提供一个经济的替代发酵系统的生产亚单位粘膜疫苗和抗体为基础的杀微生物剂。对人类的研究已经证明，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，并且植物中表达的抗体已经在粘膜攻击模型中显示出保护作用。远程 目的是研制安全有效的植物源杀微生物剂和粘膜疫苗，预防阴道内传播。我们假设，足够浓度的粘膜抗体，无论是被动管理或主动引发，可以排除阴道中的性传播病原体，从而防止传播。该项目的目标是：（a）评价阴道IgG和S-IgA的比活性成倍增加和/或100%中和100 TCID 50病原体的主动免疫策略;（B）确定通过局部施用的植物体100%中和100 TCID 50 HSV和HIV所需的粘膜抗体浓度。尽管中和活性和局部特异性抗体浓度是保护的替代措施，但该信息（与动物主动和被动免疫研究结合使用时）将促进在人体有效性试验中获得成功的产品的开发。具体目的是：（1）比较口服和阴道内给予植物源性HBsAg的安全性和特异性阴道免疫反应 以前接种过疫苗的妇女;（2）确定在女性中的安全性和特异性阴道免疫应答（3）确定在女性中粘膜施用的HSV/HIV植物抗体的安全性和时间依赖性中和活性;（4）评价植物源HBsAg/HPV或CTB-PI/HSV融合蛋白在女性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.