Webb D C, Cripps A W
Gadi Research Centre, Faculty of Applied Science, University of Canberra, Canberra City, ACT 2601, Australia.
Infect Immun. 1999 May;67(5):2138-44. doi: 10.1128/IAI.67.5.2138-2144.1999.
Nontypeable Haemophilus influenzae (NTHI) is an opportunistic pathogen, and heterogeneity in the surface-exposed immunodominant domains of NTHI proteins is thought to be associated with the failure of an infection to stimulate an immune response that is cross-protective against heterologous NTHI strains. The aim of this study was to assess the vaccine potential of a surface-exposed component of the NTHI human transferrin receptor, TbpB, and to determine if the antibody response elicited was cross-reactive with heterologous strains of NTHI. The efficacy of immunization with a recombinant form of TbpB (rTbpB) was determined by assessing the pulmonary clearance of viable bacteria 4 h after a live challenge with NTHI. There was a significant reduction in the number of viable bacteria in both the bronchoalveolar lavage fluid (34% for the 20-microgram dose and 58% for the 40-microgram dose) and lung homogenates (26% for the 20-microgram dose and 60% for the 40-microgram dose) of rats immunized with rTbpB compared to the control animals. While rTbpB-specific antibodies from immunized rats were nonspecific in the recognition of TbpB from six heterologous NTHI strains on Western blots, these antibodies differed in their ability to block transferrin binding to heterologous strains and to cross-react in bactericidal assays. If bactericidal antibodies are key indicators of the efficacy of the immune response in eliminating NTHI, this data suggests that while immunization with rTbpB stimulates protective responses against the homologous isolate, variability in the recognition of TbpB from heterologous isolates may limit the potential of rTbpB as an NTHI vaccine component.
不可分型流感嗜血杆菌（NTHI）是一种机会致病菌，人们认为NTHI蛋白表面暴露的免疫显性结构域的异质性与感染未能刺激产生针对异源NTHI菌株的交叉保护性免疫反应有关。本研究的目的是评估NTHI人转铁蛋白受体的表面暴露成分TbpB的疫苗潜力，并确定所引发的抗体反应是否与异源NTHI菌株发生交叉反应。通过评估用NTHI进行活攻毒后4小时活细菌的肺清除率，来确定重组形式的TbpB（rTbpB）免疫的效果。与对照动物相比，用rTbpB免疫的大鼠支气管肺泡灌洗液（20微克剂量组为34%，40微克剂量组为58%）和肺匀浆（20微克剂量组为26%，40微克剂量组为60%）中的活菌数量均显著减少。虽然免疫大鼠产生的rTbpB特异性抗体在蛋白质印迹法中对六种异源NTHI菌株的TbpB识别上是非特异性的，但这些抗体在阻断转铁蛋白与异源菌株结合以及在杀菌试验中交叉反应的能力上有所不同。如果杀菌抗体是免疫反应消除NTHI效力的关键指标，那么该数据表明，虽然用rTbpB免疫可刺激针对同源分离株的保护性反应，但对异源分离株TbpB识别的变异性可能会限制rTbpB作为NTHI疫苗成分的潜力。
