Development of a Vaccine for Moraxella Catarrhalis

卡他莫拉菌疫苗的研制

基本信息

批准号：
7551994
负责人：
Timothy F Murphy
金额：
$ 29.3万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-08-01 至 2011-01-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Moraxella catarrhalis is an important human respiratory tract pathogen. Approximately 25 million episodes of otitis media occur in children in the US annually; 15 to 20% of these are caused by M. catarrhalis, based on results of cultures of middle ear fluid. Otitis prone children who experience recurrent otitis media suffer from delays in speech and language development as a result of hearing loss. Chronic obstructive pulmonary disease (COPD) is now the fourth most common cause of death in the US and in the world. The course of the disease is characterized by intermittent exacerbations and many of the deaths occur as a result of exacerbations. Approximately half of exacerbations are caused by bacterial infection and M. catarrhalis is the second most common bacterial cause of exacerbations. A vaccine to prevent M. catarrhalis otitis media in children and infections in adults with COPD would have an enormous impact on morbidity and healthcare costs, and in the case of COPD, would reduce mortality. Four antigenically conserved, surface exposed outer membrane proteins have been identified as potential vaccine antigens by work supported by this grant. The overall goal of this proposal is to further evaluate these proteins as vaccine antigens and to use a powerful genomics approach to identify and study additional potential vaccine antigens for M. catarrhalis. In Specific Aim 1, genes that encode surface exposed protein antigens and that are conserved among disease-associated isolates of M. catarrhalis will be identified. In specific Aim 2, the ability of conserved, surface exposed outer membrane proteins to induce potentially protective antibodies will be assessed and the human antibody response to the proteins will be studied. In Specific Aim 3, selected proteins will be evaluated for protection in the mouse pulmonary clearance model. The goal of the work is to identify surface proteins that 1) are conserved among strains, 2) are expressed during human infection, and 3) induce protective immune responses in vitro and in vivo. In addition to identifying vaccine antigens, this work will be lead to elucidation of important information on the antigenic structure of the M. catarrhalis surface, the identification of surface antigens expressed specifically during human infection and critical information about the human immune response to surface antigens of M. catarrhalis.

描述（由申请人提供）：卡他氏菌是一种重要的人类呼吸道病原体。每年，美国儿童发生大约2500万次中耳炎。其中15％至20％是由中耳流体培养的结果引起的。由于听力损失而导致言语和语言发育的延迟，容易发生中性耳炎的儿童容易发生。慢性阻塞性肺疾病（COPD）现在是美国和世界上第四大死亡原因。该疾病的进程的特征是间歇性加重，许多死亡发生因加剧而发生。大约一半的恶化是由细菌感染引起的，而卡塔哈里斯菌是第二大最常见的细菌病因。预防CAPD成人儿童和感染的CATARRHALIS大肠杆菌介质的疫苗将对发病率和医疗保健成本产生巨大影响，而在COPD的情况下，将降低死亡率。通过该赠款支持的工作，已经将四种抗原保守的表面暴露外膜蛋白确定为潜在的疫苗抗原。该提案的总体目标是进一步评估这些蛋白质作为疫苗抗原，并使用强大的基因组学方法来识别和研究卡他甲菌的其他潜在疫苗抗原。在特定的目标1中，将鉴定出编码表面暴露的蛋白质抗原并在疾病相关的catar菌分离株中保守的基因。在特定的目标2中，将评估保守，表面暴露的外膜蛋白诱导潜在保护抗体的能力，并研究对蛋白质的人类抗体反应。在特定的目标3中，将评估选定的蛋白质在小鼠肺通量模型中进行保护。工作的目的是鉴定表面蛋白：1）在菌株中保守，2）在人类感染过程中表达，3）体外和体内诱导保护性免疫反应。除了鉴定疫苗抗原外，这项工作还将导致阐明有关卡他氏菌表面抗原结构的重要信息，在人类感染期间特别表达的表面抗原以及有关人类对cartarrhalis抗原表面抗原的免疫反应的关键信息表达的表面抗原。