Hwang Shen-An, Wilk Katarzyna M, Budnicka Monika, Olsen Margaret, Bangale Yogesh A, Hunter Robert L, Kruzel Marian L, Actor Jeffrey K
Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, TX 77030, United States.
Vaccine. 2007 Sep 17;25(37-38):6730-43. doi: 10.1016/j.vaccine.2007.07.005. Epub 2007 Jul 27.
Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a disease with world wide consequences, affecting nearly a third of the world's population. The established vaccine for TB, an attenuated strain of Mycobacterium bovis Calmette Guerin (BCG), has existed since 1921. Lactoferrin, an iron-binding protein found in mucosal secretions and granules of neutrophils was hypothesized to be an ideal adjuvant to enhance the efficacy of the BCG vaccine, specifically because of previous reports of lactoferrin enhancement of IL-12 production from macrophages infected with BCG. Different vaccination protocols were investigated for generation of host protective responses against MTB infection using lactoferrin admixed to the BCG vaccine. Resulting effects demonstrate that BCG/lactoferrin increased host protection against MTB infection by decreasing organ bacterial load and reducing lung histopathology; significant reduction in tissue CFUs and pathology were observed post-challenge compared to those seen with BCG alone. Addition of lactoferrin to the vaccine led to reduced pathological damage upon subsequent infection with virulent MTB, with positive results demonstrated when admixed in oil-based vehicle (incomplete Freund's adjuvant, IFA) or when given with BCG in saline. The observed post-challenge results paralleled increasing production of IFN-gamma and IL-6, but only limited changes to proinflammatory mediators TNF-alpha or IL-1beta from BCG-stimulated splenocytes. Overall, these studies indicate that lactoferrin is a useful and effective adjuvant to improve efficacy of the BCG vaccine, with potential to reduce related tissue damage and pulmonary histopathology.
由结核分枝杆菌（MTB）引起的结核病（TB）是一种具有全球影响的疾病，影响着近三分之一的世界人口。自1921年以来，已有的结核病疫苗是减毒牛型结核分枝杆菌卡介苗（BCG）。乳铁蛋白是一种存在于粘膜分泌物和中性粒细胞颗粒中的铁结合蛋白，由于先前有报道称乳铁蛋白可增强感染卡介苗的巨噬细胞产生白细胞介素-12，因此被认为是增强卡介苗疫苗效力的理想佐剂。研究了不同的疫苗接种方案，以使用与卡介苗疫苗混合的乳铁蛋白产生针对MTB感染的宿主保护性反应。结果表明，卡介苗/乳铁蛋白通过降低器官细菌载量和减轻肺部组织病理学来增强宿主对MTB感染的保护；与单独使用卡介苗相比，攻击后观察到组织菌落形成单位和病理学有显著减少。在疫苗中添加乳铁蛋白可减少随后感染强毒MTB时的病理损伤，当与油基载体（不完全弗氏佐剂，IFA）混合或与卡介苗在盐水中一起给药时，均显示出阳性结果。攻击后观察到的结果与干扰素-γ和白细胞介素-6的产生增加平行，但卡介苗刺激的脾细胞产生的促炎介质肿瘤坏死因子-α或白细胞介素-1β仅有有限变化。总体而言，这些研究表明乳铁蛋白是一种有用且有效的佐剂，可提高卡介苗疫苗的效力，有可能减少相关组织损伤和肺部组织病理学变化。
