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

• 批准号: 8166751
• 负责人: William Thomas Shearer
• 金额: $ 1.07万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166751
• 关键词: Address; Adherence; Adult; Age; Age-Years; Antigens; Bacterial Infections; Cells; Cessation of life; Child; Clinical Trials; Communities; Computer Retrieval of Information on Scientific Projects Database; Cytotoxic T-Lymphocytes; Data; Development; Disease; Dose; Elderly; Ensure; Epidemic; Exposure to; Family suidae; 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; Institution; Investigation; Knowledge; Lead; Lung; Measurable; Measures; Mediating; Mediator of activation protein; Medical; Memory B-Lymphocyte; Morbidity - disease rate; Nausea and Vomiting; Patients; Persons; Population; Population Study; Predisposition; Puerto Rico; Relative (related person); Reporting; Research; Research Personnel; 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; falls; high risk; immunogenicity; influenza virus vaccine; influenzavirus; interest; mortality; neutralizing antibody; pandemic disease; phase 2 study; prevent; response; seasonal influenza; young adult

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 patient s 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. The Inactivated Swine-Origin H1N1 Influenza Vaccine is safe and effective as a potential vaccine to prevent or lessen the effects of H1N1 influenza when administered to HIV Perinatally Infected Children and Youth

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 2009年甲型H1N1流感在美国的持续流行很可能会在秋冬季节大大增加，因为社交活动和气候条件更有利于流感病毒的传播。 虽然迄今为止的报告表明，健康的个体通常患有轻微疾病，但包括免疫缺陷在内的潜在医疗条件似乎会增加患严重疾病的风险，甚至会因H1N1大流行而死亡。因此，了解诺华A/H1N1 S-OIV疫苗在感染艾滋病毒的儿童和青少年中的安全性和免疫原性对于满足这一脆弱人群的卫生保健需求至关重要。 由于季节性流感已被证明会导致更严重的疾病，在艾滋病毒感染的个人相比，典型的年龄匹配的未感染的人，这是可能的，2009年甲型流感（H1N1）将导致显着的发病率和可能的死亡率在艾滋病毒感染的个人。 发病可能是流感病毒的直接结果，或者感染可能导致继发性细菌感染或由于H1N1大流行性疾病可能发生的严重恶心和呕吐而降低患者抗逆转录病毒治疗的依从性。 预防这一人群的感染至关重要。 众所周知，季节性流感感染在成年人群中广泛传播之前会影响社区中的儿童。 2009年甲型流感（H1N1）在年轻人群中对疾病的易感性似乎更加明显，因为三分之一的老年人具有可测量的血清HAI或针对2009年甲型流感（H1N1）的中和抗体水平，而年轻人和儿童完全缺乏保护滴度。血清学数据与观察结果一致，即病毒的发病率和疾病严重程度在年轻人群中似乎要高得多，而50岁以上人群具有相对保护作用。 目前正在努力评估健康儿童接种2009年甲型H1N1流感疫苗的情况。 然而，感染HIV-1的儿童上学并参加通常使儿童处于感染流感的高风险的所有活动。 保护HIV-1感染的儿童和青少年免受2009年甲型流感（H1N1）的侵害需要了解这些新产品在该人群中的安全性和免疫原性。 本研究将评估美国和波多黎各HIV-1感染儿童和青少年接种两剂诺华A/H1N1 S-OIV疫苗后的安全性和免疫应答。 认为需要两次给药，因为研究受试者既往未暴露于2009年甲型H1N1流感。由于季节性流感疫苗经常导致HIV-1感染者的反应迟钝，我们选择研究更高剂量的抗原，30 mcg，与目前正在进行的诺华A/H1N1 S-OIV疫苗在健康儿童中的试验中研究的15 mcg剂量相比。 我们还选择根据年龄将研究人群分为3组。 选择这些组是为了提供所有年龄组的信息，并且知道没有足够的把握度来比较不同年龄组的免疫应答。 本研究仅限于HIV-1围产期感染的儿童和青少年。 为了了解疾病和保护的机制，我们将研究该人群接种疫苗后的血清应答、应答持续时间和流感样疾病的发生。 我们还建议调查的细胞介导的疫苗反应。针对2009年甲型流感（H1N1）的细胞毒性T淋巴细胞（CTL）应答的产生特别令人感兴趣，因为这种病毒在肺组织中比季节性流感复制得更好，并且CTL是肺中病毒清除的主要介质。记忆B细胞对2009年甲型流感（H1N1）将确保宿主充分响应暴露于野生型病毒。 总之，2009年甲型H1N1流感很可能感染很大一部分艾滋病毒-1感染的儿童和青年，如果在感染广泛之前没有有效的疫苗。 感染可能会导致这一脆弱人群患上严重疾病，因此，疫苗接种工作至关重要。 必须在HIV-1感染儿童中确定2009年甲型H1N1流感候选疫苗的免疫原性，以确保该人群得到保护。 缺乏保护性免疫反应将支持采取额外措施保护这一高风险人群的必要性。 猪源性H1N1流感灭活疫苗是一种安全有效的潜在疫苗，可预防或减轻HIV感染的围产期儿童和青少年感染H1N1流感的影响。