Maue Alexander C, Waters W Ray, Palmer Mitchell V, Whipple Diana L, Minion F Chris, Brown Wendy C, Estes D Mark
Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65211, USA.
Vaccine. 2004 Dec 21;23(6):769-79. doi: 10.1016/j.vaccine.2004.07.019.
DNA vaccination is known to elicit robust cellular and humoral responses to encoded antigen. The co-administration of costimulatory molecules CD80 (B7-1), CD86 (B7-2) and CD154 (CD40L) has been shown to enhance immune responses in several murine models. The role of specific costimulatory molecules in non-rodent species remains incompletely characterized. In these studies, we demonstrate that the co-administration of CD80 and CD86, but not CD154, to an existing candidate subunit DNA vaccine (ESAT-6) against bovine tuberculosis, enhances protection after aerosol challenge with virulent Mycobacterium bovis. Additionally, we have shown that vaccination with M. bovis BCG is protective against tuberculosis following aerosol challenge in cattle. Two independent trials were conducted in cattle to determine the adjuvant effect of encoded antigen + CD80/CD86 and directly compare the adjuvant activities of CD80/CD86 to those of CD154. Co-administration of either CD80/CD86 or CD154 enhanced ESAT-6-specific IFN-gamma responses as compared to animals vaccinated with ESAT-6 DNA alone. However, following aerosol challenge, only animals vaccinated with CD80/CD86 possessed decreased pathology of the lungs and associated lymph nodes, as measured by gross examination, radiographic lesion morphometry and bacterial recovery. Collectively, these results demonstrate that the co-administration of costimulatory molecules with a protective antigen target enhances bovine immune responses to DNA vaccination, and that CD80/CD86 is superior to CD154 in augmenting DNA vaccine-induced protection in experimental bovine tuberculosis.
已知DNA疫苗接种可引发针对编码抗原的强大细胞和体液免疫反应。在多个小鼠模型中，共施用共刺激分子CD80（B7-1）、CD86（B7-2）和CD154（CD40L）已显示可增强免疫反应。特定共刺激分子在非啮齿动物物种中的作用仍未完全明确。在这些研究中，我们证明，将CD80和CD86（而非CD154）与现有的针对牛结核病的候选亚单位DNA疫苗（ESAT-6）共同施用，在用强毒牛分枝杆菌进行气溶胶攻击后可增强保护作用。此外，我们还表明，用卡介苗接种可在牛受到气溶胶攻击后预防结核病。在牛身上进行了两项独立试验，以确定编码抗原+CD80/CD86的佐剂效果，并将CD80/CD86与CD154的佐剂活性直接进行比较。与单独接种ESAT-6 DNA的动物相比，共施用CD80/CD86或CD154均可增强ESAT-6特异性干扰素-γ反应。然而，在气溶胶攻击后，通过大体检查、影像学病变形态测量和细菌回收测量发现，只有接种CD80/CD86的动物肺部及相关淋巴结的病变有所减轻。总体而言，这些结果表明，共刺激分子与保护性抗原靶点共同施用可增强牛对DNA疫苗接种的免疫反应，并且在增强实验性牛结核病中DNA疫苗诱导的保护作用方面，CD80/CD86优于CD154。
