Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín, San Martín, Buenos Aires, Argentina.
Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín, San Martín, Buenos Aires, Argentina.
Vaccine. 2023 May 26;41(23):3534-3543. doi: 10.1016/j.vaccine.2023.04.076. Epub 2023 May 5.
Brucellosis remains one of the most worldwide distributed zoonosis inflicting serious economical and human health problems in many areas of the world. The disease is caused by different species of the genus Brucella that have different tropisms towards different mammals being the most relevant for human health Brucella abortus, Brucella melitensis and Brucella suis that infect cows, goats/sheep, and swine respectively. For B. melitensis, considered the species with more zoonotic potential and highly aggressive for animals, only one vaccine is available to date in the market: Rev 1. This attenuated strain has the disadvantage that is has a very high residual virulence for animals and humans and, for this reason, it is applied by ocular instillation which is technically challenging in many productive settings. For this reason, the search for new vaccines for caprine and ovine brucellosis is an active topic of research. We describe here the construction of a novel highly attenuated vaccine strain (Bm Delta-pgm) that confers excellent levels of protection against B. melitensis in the mouse model of infection. This strain is a clean deletion of the phosphoglucomutase (pgm) gene that codes for a protein that catalyzes the conversion of glucose-6-P to glucose-1-P, which is used as a precursor for the biosynthesis of many polysaccharides, including the O-antigen of the lipopolysaccharide and cyclic beta glucans. Our results indicate that vaccination with Bm Delta-pgm induces a robust memory cellular immune response but no antibody production against the O-antigen. Cross protection experiments show that this new vaccine protects against B. abortus and B. suis raising the possibility that Bm Delta-pgm could be used as a universal vaccine for the most important Brucella species.
布鲁氏菌病仍然是分布最广泛的人畜共患病之一，在世界许多地区给人类健康造成严重的经济和健康问题。该疾病由不同种布鲁氏菌引起，这些菌对不同的哺乳动物有不同的倾向性，对人类健康最重要的种是布鲁氏菌流产亚种、布鲁氏菌 melitensis 和布鲁氏菌 suis，分别感染牛、山羊/绵羊和猪。对于布鲁氏菌 melitensis，被认为是具有更多人畜共患潜力和对动物高度侵袭性的物种，目前市场上只有一种疫苗：Rev 1。这种减毒株的缺点是对动物和人类的残余毒力非常高，因此它通过眼部滴注使用，在许多生产环境中具有技术挑战性。出于这个原因，寻找新的用于山羊和绵羊布鲁氏菌病的疫苗是一个活跃的研究课题。我们在这里描述了一种新型高度减毒疫苗株（Bm Delta-pgm）的构建，该疫苗株在感染的小鼠模型中对布鲁氏菌 melitensis 具有极好的保护作用。该菌株是磷酸葡萄糖变位酶（pgm）基因的清洁缺失株，该基因编码一种催化葡萄糖-6-P 转化为葡萄糖-1-P 的蛋白质，该蛋白质用于许多多糖的生物合成，包括脂多糖的 O-抗原和环状β葡聚糖。我们的结果表明，用 Bm Delta-pgm 进行疫苗接种可诱导强大的记忆细胞免疫应答，但不会针对 O-抗原产生抗体。交叉保护实验表明，这种新疫苗可预防布鲁氏菌流产亚种和布鲁氏菌 suis，这增加了 Bm Delta-pgm 可作为最重要的布鲁氏菌种的通用疫苗使用的可能性。
