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首页> 外文期刊>Infection and immunity >Immunization with high-molecular-weight adhesion proteins of nontypeable Haemophilus influenzae modifies experimental otitis media in chinchillas.
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Immunization with high-molecular-weight adhesion proteins of nontypeable Haemophilus influenzae modifies experimental otitis media in chinchillas.

机译：用不可分型流感嗜血杆菌的高分子量粘附蛋白免疫可改变龙猫的实验性中耳炎。

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Prevention of nontypeable Haemophilus influenzae otitis media by vaccination is an important health care goal. Proteins important in bacterial adherence deserve consideration as potential vaccine candidates. Two colleagues and I previously identified a family of immunogenic high-molecular-weight proteins important in adherence of nontypeable H. influenzae to human epithelial cells (J.W. St. Geme III, S. Falkow, and S.J. Barenkamp, Proc. Natl. Acad. Sci. USA, 90:2875-2879, 1993). In the work described here, I determined whether immunization with two such adherence proteins, HMW1 and HMW2, purified from prototype nontypeable Haemophilus strain 12, would modify the course of experimental otitis media caused by the homologous strain. Chinchillas received three monthly subcutaneous injections with 40 microgram of an HMW1/HMW2 protein mixture in Freud's adjuvant. One month after the last injection, animals were challenged by intrabullar inoculation with 300 CFU of nontypeable H. influenzae 12. Infection developed in five of five control animals versus 5 of 10 immunized animals (P = 0.08, Fisher exact, one-tailed). Among infected animals, bacterial counts in middle ear fluid specimens 7 days postchallenge were significantly greater in control animals than in immunized animals (P = 0.014, Mann-Whitney U test). Serum antibody titers following immunization were comparable in uninfected and infected animals. However, infection in immunized animals was uniformly associated with the appearance of bacteria downregulated in expression of the high-molecular-weight proteins, suggesting bacterial selection in response to immunologic pressure. Although protection following immunization was incomplete, these data suggest that the high-molecular-weight adhesion proteins are potentially important protective antigens which might represent one component of a multicomponent nontypeable Haemophilus vaccine.
机译：通过疫苗预防不可分型的流感嗜血杆菌性中耳炎是重要的卫生保健目标。在细菌粘附方面重要的蛋白质值得考虑作为潜在的候选疫苗。我和我的两位同事之前已经确定了一个免疫原性高分子量蛋白家族，该蛋白对不可分型流感嗜血杆菌粘附于人上皮细胞很重要（JW St. Geme III，S。Falkow和SJ Barenkamp，Proc。Natl。Acad。Sci美国，90：2875-2879，1993）。在这里描述的工作中，我确定了用从原型不可分型嗜血杆菌菌株12中纯化得到的两种这样的粘附蛋白HMW1和HMW2进行的免疫是否会改变由同源菌株引起的实验性中耳炎的病程。龙猫每月在弗洛伊德的佐剂中皮下注射40毫克HMW1 / HMW2蛋白混合物，每月三次。在最后一次注射后一个月，用300 CFU的不可分型流感嗜血杆菌12进行球内接种攻击动物，五只对照动物中有五只与十只免疫动物中的五只发生了感染（P = 0.08，Fisher精确，单尾）。在受感染的动物中，对照动物在攻击后7天中耳液样本中的细菌计数显着高于免疫动物（P = 0.014，Mann-Whitney U检验）。免疫后的血清抗体滴度在未感染和感染的动物中相当。然而，免疫动物的感染与高分子量蛋白表达中被下调的细菌的出现均匀相关，表明细菌对免疫压力的选择。尽管免疫后的保护作用是不完全的，但这些数据表明，高分子量粘附蛋白是潜在的重要保护性抗原，可能代表了多组分不可分型嗜血杆菌疫苗的一种组分。

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