Cooperative Research Partnership for an Amebic Colitis Vaccine

描述（由申请人提供）：本拨款申请是对 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, Inc 在阿米巴病应用研究方面长期合作的产物。我们共同提议开发一种无细胞疫苗并在小鼠中进行测试，用于预防因溶组织内阿米巴（NIAID B 类优先病原体）感染引起的阿米巴结肠炎。该疫苗将由溶组织内阿米巴 Gal/GalNAc 凝集素的 3 个亚基组成。关注 Gal/GalNAc 凝集素有三个主要原因：Gal/GalNAc 凝集素介导寄生虫粘附和细胞毒性，人类免疫与粘膜 IgA 抗 Gal/GalNAc 凝集素相关，以及在动物模型中接种 Gal/GalNAc 凝集素可预防阿米巴结肠炎。 并行且高度互动的项目将：（1）凭经验测试由 3 个凝集素亚基单独和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) 对目标 2 中的原型疫苗进行改造，以使用能够最佳地促进目标 2 中确定的保护性免疫机制并且可供人类使用的佐剂。请求对产品开发的早期阶段提供支持，直至但不包括第一阶段试验。 这些研究的成功完成将产生基于 Gal/GalNAc 凝集素的阿米巴病疫苗，该疫苗已准备好进行 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.