CLINICAL TRIAL: IMPAACT P1088 (VERSION 10) A PHASE II STUDY TO ASSESS THE SAFET

临床试验：IMPAACT P1088（版本 10）评估安全性的 II 期研究

基本信息

批准号：
8356737
负责人：
William Thomas Shearer
金额：
$ 1.14万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-12-01 至 2011-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8356737
关键词：
Address Adherence Adult Age Age-Years Antigens Bacterial Infections Cells Cessation of life Child Clinical Research Clinical Trials Communities Cytotoxic T-Lymphocytes Data Development Disease Dose Elderly Ensure Epidemic Exposure to Funding Generations Grant H1N1 vaccine HIV HIV-1 Healthcare IMPAACT Immune response Immunologic Deficiency Syndromes Individual Infection Infection prevention Influenza Influenza A Virus, H1N1 Subtype Investigation Knowledge Lead Lung Measurable Measures Mediating Mediator of activation protein Medical Memory B-Lymphocyte Morbidity - disease rate National Center for Research Resources Nausea and Vomiting Patients Persons Population Population Study Predisposition Principal Investigator Puerto Rico Relative (related person)Reporting Research Research Infrastructure Resources Risk ST14 gene Safety Schools Seasons Serological Serum Severity of illness Social Interaction Source Structure of parenchyma of lung Study Subject United States National Institutes of Health Vaccines Viral Virus Vulnerable Populations age group antiretroviral therapy base cost falls high risk immunogenicity influenza virus vaccine influenzavirus interest mortality neutralizing antibody pandemic disease phase 2 study response seasonal influenza young adult

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT It is very likely that the continuing epidemic spread of 2009 influenza A (H1N1) infection in the US will greatly increase in the fall-winter season when social interactions and climactic conditions become even more conducive to spread of influenza viruses. While reports to date suggest that healthy individuals typically have a mild illness, underlying medical conditions including immunodeficiency appear to increase risk for severe disease and even death with pandemic H1N1. Thus, knowledge of the safety and immunogenicity of the Novartis A/H1N1 S-OIV vaccine in HIV-infected children and youth is critically important to address the health care needs of this vulnerable population. Because seasonal influenza has been shown to cause more severe illness in HIV-infected individuals compared to that typical of age-matched uninfected people, it is likely that 2009 Influenza A (H1N1) will result in significant morbidity and possibly mortality in HIV infected individuals. Morbidity may be a direct result of the influenza virus or infection may result in secondary bacterial infections or decreased adherence to the patients antiretroviral therapy due to the severe nausea and vomiting that may occur with pandemic H1N1 illness. Prevention of infection in this population will be critical. It is well established that seasonal influenza infection impacts children in a community before becoming widespread in adult populations. Susceptibility to disease among young populations appears even more pronounced with 2009 Influenza A (H1N1) as one third of older adults have measurable levels of serum HAI or neutralizing antibody against the 2009 Influenza A (H1N1) while young adults and children completely lack protective titers. The serologic data is consistent with the observation that the attack rate and disease severity for the virus appears to be much higher in younger populations with relative protection of those 50 years of age. Efforts are currently underway to evaluate 2009 Influenza A (H1N1) vaccine in healthy children. However, HIV-1 infected children attend schools and participate in all the activities that typically put children at such high risk for infection with influenza. Protection of HIV-1 infected children and youth from 2009 Influenza A (H1N1) will require knowledge of safety and immunogenicity of these new products in this population. This study will assess the safety and immune response following each of the two doses of Novartis A/H1N1 S-OIV vaccine in HIV-1 infected children and youth in the US and Puerto Rico. Two doses are thought to be required because study subjects have had no prior exposure to 2009 Influenza A (H1N1). Because seasonal influenza vaccine often results in blunted response in HIV-1 infected persons, we have opted to investigate the higher dose of antigen, 30mcg, in comparison to the 15mcg dose that is currently being studied in ongoing trials of the Novartis A/H1N1 S-OIV vaccine in healthy children. We have also opted to stratify our study population into 3 groups based on age. The groups were selected to provide information across all age groups and with knowledge that there would be insufficient power to compare immune response across age groups. This study is limited to HIV-1 perinatally infected children and youth. In order to understand the mechanism of disease and protection, we will investigate the seroresponse, duration of response, and development of influenza-like illness following vaccine in this population. We also propose investigation of the cell-mediated response to vaccine. The generation of cytotoxic T lymphocyte (CTL) responses against 2009 Influenza A (H1N1) is of particular interest, because this virus replicates better in lung tissue than seasonal influenza and CTLs are the major mediator of viral clearance in the lungs. Memory B cells to 2009 Influenza A (H1N1) will ensure that the host responds adequately to exposure to the wild type virus. In summary, 2009 Influenza A (H1N1) is likely to infect a significant proportion of HIV-1 infected children and youth if an effective vaccine is not available before infection is widespread. Infection will likely lead to severe disease in this vulnerable population, therefore, vaccine efforts are critical. Immunogenicity of the candidate 2009 Influenza A (H1N1) vaccine must be established in HIV-1 infected children in order to assure that this population is protected. Lack of a protective immune response would support the need for additional measures to protect this high risk population.