Human Metapneumovirus Infection in Adults

描述(申请人提供)：人类偏肺病毒(HMPV)是一种新发现的呼吸道病毒，可能是导致老年人严重呼吸道疾病的未知原因。我们的初步数据表明，hMPV可能在这个年龄段的住院人数中占相当大的比例，因此值得深入研究，可能会努力开发疫苗。目前，关于hMPV在成人年龄组中的流行病学和临床影响的信息很少。作为更好地了解hMPV在成人人群中的重要性的第一步，将对最近完成的一项为期4年的成人呼吸道感染前瞻性监测研究的血清样本、鼻腔分泌物样本和临床数据进行hMPV分析。我们已经建立了灵敏、特异的实时RT-PCR和血清酶免疫分析(ELA)来诊断hMPV。总体而言，在1999年至2003年的4年期间，对1575名年轻人、健康老年人、高危成年人和长期护理机构的居民进行了跟踪调查。这些受试者接受了1428种疾病的评估，其中95%可用于hMPV分析。此外，在此期间对1330名住院受试者进行了评估。总体而言，已确认214例甲型流感和294例呼吸道合胞病毒感染。将使用EIA分析来自预期队列的季前和季后血清以及来自所有疾病的急性和恢复期血清中的hMPV感染。所有来自急性疾病的鼻分泌物都将通过RT-PCR进行hMPV检测。有症状和无症状的hMPV感染的发生率将被计算出来，并与同期在这些受试者中发现的流感和RSV感染进行比较。将分析每个成人亚组中hMPV疾病的临床特征，包括临床影响，并将其与RSV和流感进行比较。HMPV将通过毒株特异性RT-PCR鉴定为A组或B组，并将描述每种病毒株的流行病学和临床影响。除了确定成人人群中hMPV的发病率和影响外，我们还将分析血清和粘膜抗体在预防hMPV感染和严重疾病中的作用。将产生抗HMPV的单抗(MAb)，以促进建立用于研究功能性抗体的血清微量中和试验。这项研究将提供有用的数据，以确定是否需要和设计未来更大规模的老年人HMPV前瞻性研究，以及基于刺激体液免疫的疫苗的可行性。

DESCRIPTION (provided by applicant): Human metapneumovirus (hMPV) is a newly discovered respiratory virus and may be an unrecognized cause of serious respiratory illness in elderly adults. Our preliminary data suggests that hMPV may account for a substantial number of hospitalizations in this age group, and therefore is deserving of in depth study, possibly with efforts toward vaccine development. At present there is little available information about the epidemiology and clinical impact of hMPV in adult age groups. As a first step towards a better understanding of the importance of hMPV in adult populations, serum samples, nasal secretion specimens and clinical data from a recently completed 4-year prospective surveillance study of respiratory infections in several cohorts of adults will be analyzed for hMPV. We have developed sensitive and specific real time RT-PCR as well as serum enzyme immunoassay (ElA) for diagnosis of hMPV. Overall, 1575 young adults, healthy elderly, high-risk adults and residents of long term care facilities were followed during a 4 year period from 1999 - 2003. These subjects had 1428 illnesses evaluated, of which 95% are available for hMPV analysis. In addition, 1330 hospitalized subjects were evaluated during this period. Overall, 214 influenza A and 294 RSV infections were identified. Pre- and post-season sera from prospective cohorts and acute and convalescent sera from all illnesses will be analyzed for hMPV infection using an EIA. All nasal secretions from acute illnesses will be tested for hMPV by RT-PCR. The incidence of symptomatic and asymptomatic hMPV infection will be calculated and compared with influenza and RSV infections identified in these subjects during the same period. The clinical characteristics, including clinical impact, of hMPV illnesses in each of the adult subgroups will be analyzed and compared with RSV and influenza. hMPV will be identified as group A or B by strain specific RT-PCR and the epidemiology and clinical impact of each virus strain will be described. In addition to determining the incidence and impact of hMPV in adult populations we will analyze the role of serum and mucosal antibodies in protection from hMPV infection and severe disease. Monoclonal antibodies (Mabs) to HMPV will be generated to facilitate development of a serum micro neutralization assay for the study of functional antibody. This study will provide data that will be useful in determining the need for and design of future larger scale prospective studies of HMPV in the elderly as well as the feasibility of vaccines based on stimulating humeral immunity.