布鲁氏菌病,由布鲁氏菌引起的,对动物和人类健康都构成了重大的全球威胁。尽管包括S19、RB51和Rev1在内的商业活布鲁氏菌疫苗可用于动物,它们不适合人类使用和在动物中的不完全功效,因此有必要进一步研究疫苗介导的针对布鲁氏菌的免疫力。在这项研究中,我们采用体内B细胞耗竭,以及免疫缺陷和转基因小鼠模型,为了全面研究B细胞的作用,抗原摄取和呈递,抗体生产,以及在S19介导的针对布鲁氏菌病的免疫中的类别转换。我们发现抗体的产生,特别是分泌型IgM在攻击后早期以与补体激活相关的方式在S19介导的针对强毒布鲁氏菌的免疫中起保护作用。虽然滤泡辅助性T细胞缺乏在攻击的后期抑制了IgG的产生和疫苗的功效,这种效应似乎与抗体产生无关,而与T细胞功能的改变有关.相比之下,B细胞MHCII表达在攻击后稍后的时间点负面影响疫苗功效。此外,接种疫苗后B细胞耗竭,但在挑战之前,增强S19介导的针对布鲁氏菌病的保护,提示B细胞在攻击阶段的有害作用。总的来说,我们的发现表明抗体的产生是保护性的,虽然B细胞MHCII表达是有害的,针对布鲁氏菌病的活疫苗介导的免疫。重要的布鲁氏菌是一种被忽视的人畜共患病原体,分布在世界各地。我们的研究探讨了B细胞效应在活疫苗介导的免疫中对布氏杆菌病的功能。值得注意的是,我们发现了抗体的产生,尤其是分泌型IgM,在接种疫苗的小鼠中赋予对毒力布鲁氏菌的保护,这与补体激活有关。相比之下,B细胞MHCII表达负面影响疫苗功效。此外,接种疫苗后B细胞耗竭,但是在B.melitensis挑战之前,加强对感染的保护,提示在攻击阶段B细胞的有害作用。有趣的是,滤泡辅助性T细胞缺乏,这对帮助生发中心B细胞至关重要,在攻击的后期阶段降低了疫苗的效力,而与抗体的产生无关。这项研究强调了B细胞效应子功能在疫苗介导的针对布鲁氏菌的免疫中的对比和相依性作用。
Brucellosis, caused by the bacterium Brucella, poses a significant global threat to both animal and human health. Although commercial live Brucella vaccines including S19, RB51, and Rev1 are available for animals, their unsuitability for human use and incomplete efficacy in animals necessitate the further study of vaccine-mediated immunity to Brucella. In this study, we employed in vivo B-cell depletion, as well as immunodeficient and transgenic mouse models, to comprehensively investigate the roles of B cells, antigen uptake and presentation, antibody production, and class switching in the context of S19-mediated immunity against brucellosis. We found that antibody production, and in particular secretory IgM plays a protective role in S19-mediated immunity against virulent Brucella melitensis early after the challenge in a manner associated with complement activation. While T follicular helper cell deficiency dampened IgG production and vaccine efficacy at later stages of the challenge, this effect appeared to be independent of antibody production and rather was associated with altered T-cell function. By contrast, B-cell MHCII expression negatively impacted vaccine efficacy at later timepoints after the challenge. In addition, B-cell depletion after vaccination, but before the challenge, enhanced S19-mediated protection against brucellosis, suggesting a deleterious role of B cells during the challenge phase. Collectively, our findings indicate antibody production is protective, while B-cell MHCII expression is deleterious, to live vaccine-mediated immunity against brucellosis.
OBJECTIVE: Brucella is a neglected zoonotic pathogen with a worldwide distribution. Our study delves into B-cell effector functions in live vaccine-mediated immunity against brucellosis. Notably, we found antibody production, particularly secretory IgM, confers protection against virulent Brucella melitensis in vaccinated mice, which was associated with complement activation. By contrast, B-cell MHCII expression negatively impacted vaccine efficacy. In addition, B-cell depletion after vaccination, but before the B. melitensis challenge, enhanced protection against infection, suggesting a detrimental B-cell role during the challenge phase. Interestingly, deficiency of T follicular helper cells, which are crucial for aiding germinal center B cells, dampened vaccine efficacy at later stages of challenge independent of antibody production. This study underscores contrasting and phase-dependent roles of B-cell effector functions in vaccine-mediated immunity against Brucella.