EVALUATION OF MIXTURES OF PURIFIED HAEMOPHILUS-INFLUENZAE OUTER-MEMBRANE PROTEINS IN PROTECTION AGAINST CHALLENGE WITH NONTYPABLE HAEMOPHILUS-INFLUENZAE IN THE CHINCHILLA OTITIS-MEDIA MODEL
EVALUATION OF MIXTURES OF PURIFIED HAEMOPHILUS-INFLUENZAE OUTER-MEMBRANE PROTEINS IN PROTECTION AGAINST CHALLENGE WITH NONTYPABLE HAEMOPHILUS-INFLUENZAE IN THE CHINCHILLA OTITIS-MEDIA MODEL
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DOI：
10.1128/iai.61.5.1950-1957.1993
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发表时间：
1993-05-01
影响因子：
3.1
通讯作者：
DOYLE, WJ
中科院分区：
文献类型：
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作者：
GREEN, BA;VAZQUEZ, ME;DOYLE, WJ
不可分型流感嗜血杆菌（NTHi）是细菌性中耳炎的主要病原体之一，没有疫苗被证明对它有效。NTHi的三种外膜脂蛋白已被广泛研究，并且是针对该生物体的疫苗的主要候选物。Hi-PAL （P6）、重组PCP （rPCP）和e （P4）蛋白在NTHi菌株中具有抗原性保守性，可引发杀菌和保护性抗体。rPCP和Hi-PAL蛋白的基因融合也有报道。这些蛋白的混合物用于中耳炎鼠模型的主动免疫实验。用这三种脂蛋白的混合物或用rcpp - pal杂交体加e蛋白的混合物免疫龙猫。当将NTHi毒株直接注射到这些动物的中耳时，通过耳镜检查，在两组中都没有观察到对感染或疾病的保护。然而，用三种脂蛋白免疫的动物，鼓室测量的积液和炎症明显减少。通过鼓室测量和耳镜检查确定，用整个NTHi细胞或整个外膜免疫的动物，然后用同源菌株攻击，可显著保护其免受感染和疾病。与其他动物抗血清不同，纯化蛋白的鼠抗血清对NTHi没有杀菌活性，但在细胞表面固定补体。因此，栗鼠对这些脂蛋白混合物的免疫反应不同于在其他动物物种中观察到的免疫反应。这些蛋白的疫苗潜力有待进一步评估。
Nontypeable Haemophilus influenzae (NTHi) is one of the leading causative agents of bacterial otitis media, and no vaccine has been shown to be effective against it. Three outer membrane lipoproteins of NTHi have been investigated extensively and are leading candidates for inclusion in a vaccine against this organism. Hi-PAL (P6), recombinant PCP (rPCP), and e (P4) proteins are antigenically conserved among NTHi strains and elicit bactericidal and protective antibodies. A genetic fusion of the rPCP and Hi-PAL proteins has also been reported. Mixtures of these proteins were used for active immunization experiments in the chinchilla model of otitis media. Chinchillas were immunized either with a mixture of all three lipoproteins or with the mixture of rPCP-PAL hybrid plus e protein. When these animals were challenged with a NTHi strain injected directly into the middle ears, no protection from infection or disease, as measured by otoscopy, was observed in either group. However, effusion and inflammation measured by tympanometry were significantly reduced in animals immunized with the three lipoproteins. Animals that had been immunized with either whole NTHi cells or total outer membranes and then challenged with the homologous strain were significantly protected from both infection and disease, as determined by tympanometry and otoscopy. Unlike other animal antisera, chinchilla antisera against the purified proteins had no bactericidal activity against NTHi but did fix complement on the cell surface. Thus, the chinchilla immune responses to mixtures of these lipoproteins differ from the immune responses observed in other animal species. Further evaluation of these proteins for their vaccine potential remains to be done.