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Lactoferrin as an Adjuvant for Cellular Immunity

乳铁蛋白作为细胞免疫佐剂

基本信息

批准号：
6552378
负责人：
JEFFREY K ACTOR
金额：
$ 10万
依托单位：
PHARMAREVIEW CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-15 至 2004-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6552378
关键词：
Bacillus Calmette Guerin vaccine cellular immunity immunologic substance development /preparation immunomodulators interleukin 12 interleukin 15 laboratory mouse lactoferrin tumor necrosis factor alpha vaccine development veterinary medicine

项目摘要

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.

描述(由申请人提供)：该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。我们将具体讨论乳铁蛋白作为佐剂的有效性，以增强卡介苗接种后应对结核分枝杆菌毒力攻击的效果。改进的无毒佐剂，特别是能够诱导(CM)的佐剂，需要用于研究用途以及开发人类和兽医疫苗。明矾是唯一一种获准人类使用的佐剂，可以有效地促进抗体的形成，但很少能有效地诱导CMI。其他确实会诱发CMI的佐剂，如皂苷和完全弗氏佐剂，毒性太大，不能在人类身上使用，正在逐步限制在动物身上使用。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；它是一种直接参与宿主防御的效应分子。现有证据表明，乳铁蛋白参与免疫反应的诱导，尤其是CMI。初步研究表明，乳铁蛋白作为佐剂可剂量依赖性地增强小鼠迟发型超敏反应，且毒性低。此外，它还诱导巨噬细胞产生IL-12、IL-15和TNF-α，从而形成一个可能推动免疫反应向CMI发展的局部环境。