LUNAM Université, Unité Fonctionnalité et Ingénierie des Protéines, Nantes, France.
Pathog Dis. 2013 Mar;67(2):136-58. doi: 10.1111/2049-632X.12022. Epub 2013 Feb 25.
Worldwide, in endemic areas of cholera, the group most burdened with cholera is children. This is especially vexing as young children (2-5 years of age) do not respond as well, or for as long as adults do, to the current killed oral cholera vaccines (OCV). Conjugate vaccines based on the hapten-carrier paradigm have been developed for several bacterial pathogens that cause widespread and severe diseases in young children. We and others have studied different formulations of Vibrio cholerae (Vc) O1 lipopolysaccharide (LPS, a T-independent antigen) conjugates. Detoxified LPS is a central component of a LPS-based conjugate vaccine. pmLPS, which is detoxified by acid treatment, is a superior immunogen compared with hydrazine-detoxified LPS (DetAcLPS) that has altered lipid A acyl chains. The other feature of pmLPS is the ability to link carrier proteins to a core region of sugar. pmLPS readily induced vibriocidal antibodies following one intraperitoneal dose in a MPL-type adjuvant One dose of the pmLPS conjugate was suggestive of being protective; a booster resulted in protective antibodies for infant mice challenged with virulent cholera.
在霍乱流行地区,全世界受霍乱影响最严重的群体是儿童。这尤其令人烦恼,因为幼儿(2-5 岁)对目前的口服霍乱死疫苗(OCV)的反应不如成年人持久。针对几种引起幼儿广泛和严重疾病的细菌病原体,已经开发出基于半抗原载体模式的结合疫苗。我们和其他人研究了不同配方的霍乱弧菌(Vc)O1 脂多糖(LPS,一种 T 非依赖性抗原)结合物。解毒 LPS 是基于 LPS 的结合疫苗的核心成分。与酰链发生改变的肼解毒 LPS(DetAcLPS)相比,经酸处理解毒的 pmLPS 是一种更有效的免疫原。pmLPS 的另一个特点是能够将载体蛋白与糖的核心区域连接起来。在 MPL 型佐剂中,单次腹腔内给药后,pmLPS 可迅速诱导杀菌抗体。一剂 pmLPS 结合物可提示具有保护作用;加强针可使婴儿小鼠对强毒霍乱的挑战产生保护性抗体。