Cooperative Research Partnership for an Amebic Colitis Vaccine

描述（由申请人提供）：本资助申请是对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。我们一起建议在小鼠中开发和测试一种无细胞疫苗，用于预防由溶组织内阿米巴（NIAID B类优先病原体）感染引起的阿米巴结肠炎。疫苗将由构成E.溶组织Gal/GalNAc凝集素。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，人类免疫与粘膜伊加抗Gal/GalNAc凝集素相关，以及用Gal/GalNAc凝集素接种疫苗可在动物模型中保护免受阿米巴结肠炎。 平行和高度互动的项目将：（1）经验性地测试由3种凝集素亚基中的每一种单独和组合组成的无细胞疫苗;（2）系统地研究小鼠获得性免疫的机制;（3）调整目标2的原型疫苗，以使用最佳促进目标2中确定的保护性免疫机制的佐剂，并可供人类使用。要求对产品开发的早期阶段提供支助，直至但不包括第一阶段试验。 这些研究的成功完成将产生用于阿米巴病的基于Gal/GalNAc凝集素的疫苗，该疫苗准备用于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.