Lactoferrin as an Adjuvant for Cellular Immunity

描述（由申请方提供）：本项目的总体目标是开发牛和人乳铁蛋白作为佐剂，以增强抗体和细胞介导的免疫力。 我们将特别讨论乳铁蛋白作为佐剂的功效，以增强卡介苗接种的功效，以应对随后的强毒结核分枝杆菌的挑战。 需要改进的无毒佐剂，特别是能够诱导（CM）的佐剂用于研究用途以及用于开发人和兽用疫苗。 唯一批准用于人类的佐剂明矾有效地增强抗体形成，但很少有效地诱导CMI。 其他佐剂，如皂苷和完全弗氏佐剂，确实诱导CMI，对人类使用毒性太大，在动物中逐渐受到限制。 乳铁蛋白不同于微生物衍生佐剂，也不同于细胞因子和生长因子;它是直接参与宿主防御的效应分子。现有的证据表明乳铁蛋白参与诱导免疫应答，尤其是CMI。 初步研究表明，乳铁蛋白作为佐剂以剂量依赖性方式增强小鼠迟发型超敏反应（DTH），并且具有低毒性。 此外，它诱导巨噬细胞产生IL-12、IL-15和TNF-α，从而产生可能将免疫应答推向CMI发展的局部环境。

DESCRIPTION (provided by applicant): The overall goal of this project is to develop bovine and human Lactoferrins as an adjuvant to augment antibody and cell mediated immunity. We will specifically address the efficacy of Lactoferrin as an adjuvant to augment efficacy of BCG vaccination to subsequent challenge with virulent Mycobacterium tuberculosis. Improved nontoxic adjuvants, especially adjuvants capable of inducing (CM are needed for research use and for development of human and veterinary vaccines. The only adjuvant licensed for human use, alum, effectively enhances antibody formation, but is seldom effective for inducing CMI. Other adjuvants such as saponin and Complete Freund's that do induce CMI are much too toxic for use in humans and are being progressively restricted in animals. Lactoferrin is different from microbial derivative adjuvants, and from cytokines and growth factors; it is an effector molecule that directly participates in host defenses. Available evidence indicatesLactoferrin participates in the induction of immune responses, especially CMI. Preliminary studies demonstrate that lactoferrin as an adjuvant enhances delayed type hypersensitivity (DTH) in mice in a dose dependent fashion and has low toxicity. Furthermore, it induces IL-12, IL-15 and TNF-a production by macrophages thereby generating a local environment likely to push immune responses towards development of CMI.