Villeneuve Sylvain, Boutonnier Alain, Mulard Laurence A, Fournier Jean-Michel
Unité du Choléra et des Vibrions, Centre National de Référence des Vibrions et du Choléra1, and Unité de Chimie Organique2, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France.
Microbiology (Reading). 1999 Sep;145 ( Pt 9):2477-2484. doi: 10.1099/00221287-145-9-2477.
Cholera remains an important public health problem in many parts of the world and the availability of an effective cholera vaccine is important for the prevention of cholera in the countries affected by this disease. Despite the appearance in 1992 of a new serogroup, 0139, of Vibrio cholerae, most of the cholera outbreaks are still caused by V. cholerae O1 biotype El Tor. Vaccine trials in Asia from 1968 to 1971, and studies of the production of serotype-specific antiserum in rabbits and of the protective activity of monoclonal antibodies against diarrhoeal disease in neonatal mice, have led to the conclusion that the Ogawa serotype contains a specific antigenic determinant whereas the Inaba serotype contains a different antigenic determinant that cross-reacts with the Ogawa serotype. By studying the binding of anti-Ogawa monoclonal antibodies to synthetic oligosaccharide fragments mimicking the Ogawa O-specific polysaccharide, it has been shown that the terminal monosaccharide, bearing the 2-O-methyl group in the O-specific polysaccharide, is most probably the serotype-specific determinant for the Ogawa strain. However, study of the binding of a monoclonal antibody recognizing both Ogawa and Inaba serotypes suggested partial recognition of the core as well as of the O-specific polysaccharide of the LPS of V. cholerae O1. To further characterize this antigenic determinant that is common to the Ogawa and Inaba serotypes, the core and the O-specific polysaccharide linked to the core of V. cholerae O1 LPS were purified by preparative electrophoresis. The O-specific polysaccharide linked to the core was subjected to periodate oxidation to destroy sugars from the core. Binding studies of these purified saccharide fragments to a monoclonal antibody which is protective in mice and specific to the antigenic determinant common to Ogawa and Inaba serotypes showed that both the core and the O-specific polysaccharide are involved in this common antigenic determinant. This explains how the presence or the absence of the Ogawa-specific antigenic determinant would lead to the expression of two independent antigenic determinants of V. cholerae O1, one specific to the Ogawa serotype and the other common to both Ogawa and Inaba serotypes.
霍乱在世界许多地区仍然是一个重要的公共卫生问题，有效的霍乱疫苗对于受该疾病影响国家预防霍乱至关重要。尽管1992年出现了霍乱弧菌的新血清型O139，但大多数霍乱疫情仍由霍乱弧菌O1生物型埃尔托引起。1968年至1971年在亚洲进行的疫苗试验，以及对兔血清型特异性抗血清生产和单克隆抗体对新生小鼠腹泻病保护活性的研究，得出结论：小川血清型含有特定抗原决定簇，而稻叶血清型含有与小川血清型交叉反应的不同抗原决定簇。通过研究抗小川单克隆抗体与模拟小川O特异性多糖的合成寡糖片段的结合，已表明在O特异性多糖中带有2-O-甲基的末端单糖很可能是小川菌株的血清型特异性决定簇。然而，对一种识别小川和稻叶血清型的单克隆抗体结合的研究表明，该抗体部分识别霍乱弧菌O1脂多糖的核心以及O特异性多糖。为了进一步表征小川和稻叶血清型共有的这种抗原决定簇，通过制备电泳纯化了与霍乱弧菌O1脂多糖核心相连的核心和O特异性多糖。将与核心相连的O特异性多糖进行高碘酸盐氧化以破坏来自核心的糖。这些纯化的糖片段与一种在小鼠中具有保护作用且对小川和稻叶血清型共有的抗原决定簇特异的单克隆抗体的结合研究表明，核心和O特异性多糖都参与了这种共同抗原决定簇。这解释了小川特异性抗原决定簇的存在或缺失如何导致霍乱弧菌O1的两个独立抗原决定簇的表达，一个是小川血清型特异性的，另一个是小川和稻叶血清型共有的。
