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首页> 外文期刊>Infection and immunity >Preparation, Immunogenicity, and Protective Efficacy, in a Murine Model, of a Conjugate Vaccine Composed of the Polysaccharide Moiety of the Lipopolysaccharide of Vibrio cholerae O139 Bound to Tetanus Toxoid
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Preparation, Immunogenicity, and Protective Efficacy, in a Murine Model, of a Conjugate Vaccine Composed of the Polysaccharide Moiety of the Lipopolysaccharide of Vibrio cholerae O139 Bound to Tetanus Toxoid

机译:在鼠模型中,由霍乱弧菌O139脂多糖结合到破伤风类毒素的多糖部分组成的共轭疫苗的制备,免疫原性和保护功效

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The epidemic and pandemic potential of Vibrio choleraeO139 is such that a vaccine against this newly emerged serogroup ofV. cholerae is required. A conjugate made of the polysaccharide moiety (O-specific polysaccharide plus core) of the lipopolysaccharide (LPS) of V. cholerae O139 (pmLPS) was prepared by derivatization of the pmLPS with adipic acid dihydrazide and coupling to tetanus toxoid (TT) by carbodiimide-mediated condensation. The immunologic properties of the conjugate were tested using BALB/c mice injected subcutaneously three times at 2 weeks interval and then a fourth time 4 weeks later. Mice were bled 7 days after each injection and then once each month for the following 6 months. LPS and TT antibody levels were determined by enzyme-linked immunosorbent assay using immunoplates coated with either O139 LPS or TT. Both pmLPS and pmLPS-TT conjugate elicited low levels of immunoglobulin M (IgM), peaking 5 weeks after the first immunization. The conjugate elicited high levels of IgG antibodies, peaking 3 months after the first immunization and declining slowly during the following 5 months. TT alone, or as a component of conjugate, induced mostly IgG antibodies. Antibodies elicited by the conjugate recognized both capsular polysaccharide and LPS from V. cholerae O139 and were vibriocidal. They were also protective in the neonatal mouse model of cholera infection. The conjugation of the O139 pmLPS, therefore, enhanced its immunogenicity and conferred T-dependent properties to this polysaccharide.
机译:霍乱弧菌O139的流行和大流行潜力使针对这种新出现的 V血清群的疫苗成为可能。霍乱是必需的。由 V的脂多糖(LPS)的多糖部分(O特异性多糖加核)制成的缀合物。通过用己二酸二酰肼将pmLPS衍生化并通过碳二亚胺介导的缩合偶联到破伤风类毒素(TT)上来制备霍乱O139(pmLPS)。用BALB / c小鼠以2周间隔皮下注射3次,然后4周后第四次皮下注射,测试缀合物的免疫学特性。每次注射后7天将小鼠放血,然后在接下来的6个月中每月一次放血。使用涂有O139 LPS或TT的免疫板通过酶联免疫吸附测定法确定LPS和TT抗体水平。 pmLPS和pmLPS-TT缀合物均引起低水平的免疫球蛋白M(IgM),在首次免疫后5周达到峰值。该结合物引发高水平的IgG抗体,在第一次免疫后3个月达到峰值,在随后的5个月内缓慢下降。单独的TT或作为缀合物的组分,主要诱导IgG抗体。由缀合物引发的抗体识别荚膜多糖和来自 V的LPS。 O139和霍乱弧菌。它们在霍乱感染的新生小鼠模型中也具有保护作用。因此,O139 pmLPS的结合增强了其免疫原性,并赋予了该多糖以T依赖性的特性。

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