Cooperative Research Partnership for an Amebic Colitis Vaccine

描述（由申请人提供）：此拨款申请是对RFA AI-05-019“生物防御合作研究伙伴关系”的回应。它是弗吉尼亚大学和TechLab公司在阿米巴病应用研究方面长期合作的产物。我们建议共同开发并在小鼠中测试一种非细胞疫苗，用于预防由溶组织内阿米巴感染引起的阿米巴结肠炎，这是NIAID B类优先病原体。该疫苗将由构成溶组织芽胞杆菌Gal/GalNAc凝集素的3个亚基组成。关注Gal/GalNAc凝集素主要有三个原因：Gal/GalNAc凝集素介导寄生虫粘附和细胞毒性，人类免疫与黏膜IgA抗Gal/GalNAc凝集素有关，在动物模型中接种Gal/GalNAc凝集素可预防阿米巴性结肠炎。平行和高度互动的项目将：(1)经验性地测试由3种凝集素亚基单独或组合组成的非细胞疫苗；(2)系统研究小鼠获得性免疫机制；(3)调整Aim 2的原型疫苗，使其使用佐剂，以最佳方式促进Aim 2中确定的保护性免疫机制，并可用于人类。支持产品开发的早期阶段，直到但不包括第一阶段的试验。这些研究的成功完成将导致基于Gal/GalNAc凝集素的阿米巴病疫苗准备进行GMP生产和I期研究。

DESCRIPTION (provided by applicant): This grant application is in response to RFA AI-05-019 "Cooperative Research Partnerships for Biodefense". It is a product of the long-standing partnership of the University of Virginia and TechLab, Inc in applied research on amebiasis. Together we propose to develop and test in mice an acellular vaccine for the prevention of amebic colitis due to infection with Entamoeba histolytica, an NIAID Category B priority pathogen. The vaccine will be composed from the 3 subunits that comprise the E. histolytica Gal/GalNAc lectin. Focus on the Gal/GalNAc lectin is for three major reasons: the Gal/GalNAc lectin mediates parasite adherence and cytotoxicity, human immunity is associated with mucosal IgA anti-Gal/GalNAc lectin, and vaccination with the Gal/GalNAc lectin protects from amebic colitis in an animal model. Parallel and highly interactive projects will: (1) empirically test acellular vaccines comprised of each of the 3 lectin subunits alone and in combination; (2) systematically investigate mechanisms of acquired immunity in the mouse; and (3) adapt the prototype vaccine from Aim 2 for the use of adjuvants that optimally promote the mechanisms of protective immunity identified in Aim 2 and which are acceptable for human use. Support is requested for the early stages of product development, up to but not including phase I trails. Successful completion of these studies will result in a Gal/GalNAc lectin-based vaccine for amebiasis that is ready for GMP production and phase I studies.