Department of Pathology, Medical School, University of Texas-Houston Medical School, Houston, TX 77030, USA.
Tuberculosis (Edinb). 2009 Dec;89 Suppl 1:S49-54. doi: 10.1016/S1472-9792(09)70012-5.
The current vaccine for tuberculosis (TB), an attenuated strain of Mycobacterium bovis Bacillus Calmette Guerin (BCG), is effective to prevent childhood onset of the disease, but its efficacy is reduced in adults. One strategy to improve the existing vaccine is to develop more effective adjuvants. Lactoferrin, an iron-binding glycoprotein possessing immune modulatory activities, is a promising adjuvant candidate. The studies presented here examine the effect of lactoferrin to enhance efficacy of the BCG vaccine using a vaccination/challenge protocol (8 weeks boost and challenge at 12 weeks post-boost) that focuses on reduction in development of pathological changes to lung tissue. C57BL/6 and BALB/c mice vaccinated with BCG/lactoferrin exhibited protection upon Mycobacterium tuberculosis (MTB) challenge, showing reduced pulmonary disease pathology and decreased organ bacterial load. In addition, BCG/lactoferrin-treated macrophages isolated from BALB/c mice, which express a relative reduced T(H)1 phenotypic response to MTB antigens compared to the C57BL/6 mouse, were able to activate a higher percentage of IFN-gamma-producing CD4+ splenocytes. Overall, lactoferrin stands as an adjuvant capable of enhancing efficacy of the BCG vaccine through induction of T(H)1 immune responses, even in hosts typically demonstrative of reduced T(H)1 responsiveness to BCG antigens.
当前用于预防结核病（TB）的疫苗是减毒牛型分枝杆菌卡介苗（BCG），对儿童发病有一定预防效果，但对成人效果不佳。改善现有疫苗的一种策略是开发更有效的佐剂。乳铁蛋白是一种具有免疫调节活性的铁结合糖蛋白，是一种很有前途的佐剂候选物。本研究采用接种/攻毒方案（接种后 8 周加强免疫，12 周后攻毒），重点研究减少肺部组织病理性改变，来评估乳铁蛋白增强 BCG 疫苗效力的效果。用 BCG/乳铁蛋白免疫的 C57BL/6 和 BALB/c 小鼠在受到结核分枝杆菌（MTB）攻毒后得到保护，显示出肺部疾病病理学改变减少，器官细菌载量降低。此外，与 C57BL/6 小鼠相比，BALB/c 小鼠来源的表达相对较低的 MTB 抗原 T(H)1 表型应答的 BCG/乳铁蛋白处理的巨噬细胞能够激活更高比例的 IFN-γ产生 CD4+ 脾细胞。总体而言，乳铁蛋白作为一种佐剂能够通过诱导 T(H)1 免疫应答来增强 BCG 疫苗的效力，即使在对 BCG 抗原表现出相对较低的 T(H)1 应答的宿主中也是如此。
