Cooperative Research Partnership for an Amebic Colitis Vaccine

描述(申请人提供)：此资助申请是对RFA AI-05-019“生物防御合作研究伙伴关系”的响应。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。我们共同建议开发一种无细胞疫苗并在小鼠身上进行测试，以预防因感染溶组织内阿米巴而引起的阿米巴结肠炎，内阿米巴是一种NIAID B类优先病原体。该疫苗将由3个亚基组成，这些亚基组成了溶组织性肠杆菌Gal/GalNAc凝集素。关注Gal/GalNAc凝集素主要有三个原因：Gal/GalNAc凝集素介导寄生虫黏附和细胞毒性，人类免疫与粘膜IgA抗Gal/GalNAc凝集素相关，以及Gal/GalNAc凝集素疫苗预防动物模型阿米巴结肠炎。平行和高度互动的项目将：(1)经验性地测试由3个凝集素亚基中的每一个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；以及(3)使来自目标2的原型疫苗用于使用佐剂，这些佐剂最佳地促进目标2中确定的保护性免疫机制，并且是人类可以接受的。要求为产品开发的早期阶段提供支持，直至(但不包括)第一阶段。这些研究的成功完成将导致一种基于Gal/GalNAc凝集素的阿米巴病疫苗，该疫苗可用于GMP生产和第一阶段研究。

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.