Meier Patricia Stutzmann, Freiburghaus Simone, Martin Andrea, Heiniger Nadja, Troller Rolf, Aebi Christoph
Institute for Infectious Diseases, University of Bern, Switzerland.
Pediatr Infect Dis J. 2003 Mar;22(3):256-62. doi: 10.1097/01.inf.0000054827.86683.bd.
Moraxella catarrhalis is an important cause of otitis media. A number of candidate antigens for a future infant otitis media vaccine have been identified, but their mucosal immunogenicity induced by nasopharyngeal M. catarrhalis colonization has not been characterized. The aim of this study was to determine the salivary IgA response to M. catarrhalis outer membrane proteins (OMP) in young children.
Children ages 1 to 24 months evaluated for acute respiratory tract infection were prospectively enrolled. M. catarrhalis nasopharyngeal colonization was determined by (1) selective culture and (2) detection by reverse transcription-PCR of messenger RNA specific for the OMP UspA1 and UspA2. Salivary IgA responses were detected by immunoblot analysis of M. catarrhalis OMP. Isogenic knockout mutants for UspA1, UspA2, hemagglutinin (Hag), transferrin-binding protein B (TbpB) and CopB were constructed for identification of specific target OMP.
Sixty-six patients were studied. The rates of M. catarrhalis colonization by culture, reverse transcription-PCR for messenger RNA and mRNA were 40, 94 and 58%, respectively. Anti-M. catarrhalis salivary IgA was detected in 62 patients (94%). IgA directed against a >250-kDa antigen (assigned to UspA1/UspA2 by mutant analysis) and a 200-kDa antigen (Hag) were detected in 65 and 70% of patients, respectively. Bands at 80 to 85 kDa (82%) consisted of IgA directed against monomeric UspA2, TbpB and CopB.
colonization occurring in early infancy is associated with a consistent mucosal immune response directed against the UspA proteins, Hag and other OMP. The data suggest that several M. catarrhalis OMP are immunogens of the nasopharyngeal mucosal immune system of infants.
卡他莫拉菌是中耳炎的重要病因。已鉴定出多种未来婴儿中耳炎疫苗的候选抗原,但尚未对其由鼻咽部卡他莫拉菌定植诱导的黏膜免疫原性进行表征。本研究的目的是确定幼儿对卡他莫拉菌外膜蛋白(OMP)的唾液IgA反应。
前瞻性纳入1至24个月因急性呼吸道感染接受评估的儿童。通过(1)选择性培养和(2)逆转录PCR检测OMP UspA1和UspA2特异性信使RNA来确定卡他莫拉菌的鼻咽部定植情况。通过对卡他莫拉菌OMP的免疫印迹分析检测唾液IgA反应。构建UspA1、UspA2、血凝素(Hag)、转铁蛋白结合蛋白B(TbpB)和CopB的同基因敲除突变体以鉴定特定的目标OMP。
对66例患者进行了研究。通过培养、信使RNA逆转录PCR和mRNA检测卡他莫拉菌定植的发生率分别为40%、94%和58%。62例患者(94%)检测到抗卡他莫拉菌唾液IgA。分别在65%和70%的患者中检测到针对>250 kDa抗原(通过突变分析确定为UspA1/UspA2)和200 kDa抗原(Hag)的IgA。80至85 kDa的条带(82%)由针对单体UspA2、TbpB和CopB的IgA组成。
婴儿早期发生的定植与针对UspA蛋白、Hag和其他OMP的持续黏膜免疫反应相关。数据表明,几种卡他莫拉菌OMP是婴儿鼻咽部黏膜免疫系统的免疫原。