Plant Based Microbicides and Vaccines to Prevent STIs

预防性传播感染的植物杀微生物剂和疫苗

• 批准号: 7115284
• 负责人: Carol Tacket
• 金额: $ 38.88万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7115284
• 关键词: AIDS vaccines; Alphaherpesvirinae; active immunization; antibody formation; antiviral antibody; biological products; biotechnology; clinical trial phase I; cooperative study; drug screening /evaluation; female; hepatitis B antigens; human immunodeficiency virus 1; human papillomavirus; human subject; immunoglobulin A; immunoglobulin G; immunologic substance development /preparation; mucosal immunity; neutralizing antibody; oral administration; patient oriented research; recombinant proteins; sexually transmitted diseases; topical drug application; viral vaccines

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.

基于抗体的微生物和粘膜疫苗具有拍卖的共同机制，即对病原体，常见调节和临床试验的免疫排除以及与生物药物对低成本/大容量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微生物剂提供发酵系统的经济替代方法。在人类中的研究表明，在植物中产生的疫苗抗原可以刺激在植物中表现出的血清和粘膜分泌物中抗原特异性抗体的产生，并且在粘膜挑战模型中显示了保护。远程 目的是开发安全有效的植物性杀菌剂和粘膜疫苗，以防止阴道传播。我们假设被动施用或积极引起的足够浓度的粘膜抗体可以排除阴道中的性传播病原体，从而预防传播。该项目的目标是：（a）评估阴道IgG和S-IgA的特异性活动的积极免疫策略，以及/或100％中和100 TCID 50的病原体中和/或100％中和； （b）确定通过局部应用植物体对100％HSV和HIV中和100％中和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度量，但此信息（与动物的主动和被动免疫研究相结合时）将增强在人体功效试验中将成功的产品的发展。具体目的是：（1）比较口服和静脉内给药的植物衍生的HBSAG的安全性和特定的阴道免疫反应 以前接种妇女； （2）在女性中确定口服和阴道给药的，特异性IgG，IgA和S-IgA的安全性和特定的阴道免疫反应（通过中和抗体活性，特异性IgG，IgA和S-IgA），植物衍生的CTB-P1，一种粘膜HIV疫苗； （3）确定女性的安全性和时间依赖性的中和粘液施用的HSV/HIV植物植物的活性； （4）在女性中评估植物来源的HBSAG/HPV或CTB-PI/HSV融合蛋白的安全性和免疫原性。