首页> 外文期刊>Infection and immunity >Laboratory and clinical evaluation of conjugate vaccines composed of Staphylococcus aureus type 5 and type 8 capsular polysaccharides bound to Pseudomonas aeruginosa recombinant exoprotein A.
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Laboratory and clinical evaluation of conjugate vaccines composed of Staphylococcus aureus type 5 and type 8 capsular polysaccharides bound to Pseudomonas aeruginosa recombinant exoprotein A.

机译:由金黄色葡萄球菌5型和8型荚膜多糖与铜绿假单胞菌重组外蛋白A结合而成的结合疫苗的实验室和临床评估。

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The synthesis, standardization, and immunogenicity in young outbred mice and clinical evaluation in adult volunteers of investigational vaccines designed to induce serum antibodies to the type 5 and type 8 capsular polysaccharides (CPs) of Staphylococcus aureus are described. Conjugates composed of the type 5 CP and a sonicated preparation of a high-molecular-weight type 8 CP bound to a nontoxic recombinant protein derived from Pseudomonas aeruginosa exotoxin A (rEPA) were synthesized. The conjugates were nontoxic and elicited serum CP antibodies after two subcutaneous injections into young outbred mice; a third injection elicited a booster response. The lower-molecular-weight type 8 CP was not immunogenic in the mice, and the high-molecular-weight type 8 CP elicited low levels of antibodies without a booster effect. In the volunteers, neither the conjugates nor the type 8 CP alone caused significant local reactions or fever. The conjugates elicited type-specific antibodies of both the immunoglobulin M (IgM) and IgG classes after the first injection; a second injection 6 weeks later did not stimulate a booster effect. The high-molecular-weight type 8 CP alone, injected once only, elicited levels of IgG and IgM type-specific antibodies similar to those of the conjugate. The vaccine-induced CP antibodies were mostly of the IgG1 and IgG2 subclasses and had opsonophagocytic activity. The conjugates elicited IgG antibodies to the native exotoxin A with neutralizing activity. In summary, the type 5 and type 8 conjugates were safe and elicited biologically active antibodies to both the CP and rEPA components.
机译:描述了年轻近交小鼠的合成,标准化和免疫原性,以及成年志愿者的临床评估,这些研究疫苗旨在诱导针对金黄色葡萄球菌的5型和8型荚膜多糖(CP)的血清抗体。合成了由5型CP和结合到铜绿假单胞菌外毒素A(rEPA)的无毒重组蛋白上的高分子量8型CP的超声处理组成的结合物。偶联物是无毒的,在两次皮下注射给年轻的近交小鼠后引起血清CP抗体。第三次注射引起加强反应。较低分子量的8 CP型在小鼠中不是免疫原性的,而较高分子量的8 CP型则产生低水平的抗体而没有增强作用。在志愿者中,结合物和8型CP均未引起明显的局部反应或发烧。第一次注射后,结合物引发了免疫球蛋白M(IgM)和IgG类的类型特异性抗体。 6周后第二次注射没有刺激增强作用。单独注射一次的高分子量8型CP引起的IgG和IgM型特异性抗体水平与结合物相似。疫苗诱导的CP抗体大部分为IgG1和IgG2亚类,并具有调理吞噬作用。结合物引发具有中和活性的针对天然外毒素A的IgG抗体。总而言之,5型和8型偶联物是安全的,并且针对CP和rEPA组分均产生了生物活性抗体。

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