CLINICAL TRIAL: IMPAACT 1065 PHASE I/II STUDY OF SAFETY AND IMMUNOGENICITY OF QU

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来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 FDA最近批准的四价脑膜炎球菌结合疫苗（MCV4）已导致建议在青春期前访问时接种11 - 12岁的个体，进入高中（约15岁）的个体和住在宿舍的新生，认识到青春期期间脑膜炎球菌疾病风险增加。 由于大多数围产期获得性HIV感染的儿童已进入青春期，并且美国大多数新发儿科HIV感染发生在青少年年龄组，因此针对脑膜炎球菌免疫接种患者的新的基于年龄的建议将导致大多数HIV感染的青少年符合接种疫苗的年龄条件，而HIV感染人群没有安全性或免疫原性数据。 这项I/II期研究将评估MCV-4在296名艾滋病毒感染青年中的安全性和免疫原性，这些青年的年龄在8805岁至1000岁之间。11和<25岁。本研究还旨在回答与HIV感染青年免疫接种相关的几个重要问题，包括短期和长期免疫原性。 主要目标是：比较单次给药方案与两次给药方案在28周时HIV-1感染青年中MCV4的免疫原性，其中免疫原性应答定义为血清杀菌抗体滴度增加4倍或更高;估计短期内第1组HIV-1感染青年中MCV4疫苗的免疫原性（4周和24周）（CD4%\ul>\ulnone 15）;估计长期（72周时）MCV4疫苗在HIV-1感染青年中的免疫原性;评价MCV4疫苗在HIV-1感染青年中的安全性，包括接种疫苗后的短期局部和全身反应。 假设 在HIV感染的青年中进行MCV-4免疫接种将是安全的，并且对于具有CD4%<15的青年，疫苗在单剂量方案中将是免疫原性的，但是对于具有CD4%<15的青年，免疫原性将需要两个剂量。 具体目标 比较四价脑膜炎球菌结合疫苗（MCV4）单次给药方案与两次给药方案在28周时HIV-1感染青年中的免疫原性，其中免疫原性应答定义为血清杀菌抗体滴度增加4倍或更高; 估计第1组HIV-1感染青年中MCV4疫苗的短期（4周和24周）免疫原性（CD4%> 15）; 估计MCV4疫苗在HIV-1感染青年中的长期（72周）免疫原性; 评价MCV4疫苗在HIV-1感染青年中的安全性，包括接种疫苗后的短期局部和全身反应。 检查HIV-1感染青年中MCV4的短期和长期免疫原性是否随研究受试者接种疫苗时的免疫状态而变化; 比较第1组中1剂与2剂方案的HIV-1感染青年中MCV4的长期免疫原性（72周时）（CD4%\ul>\ul 15） 基于接种时的CD4%，评价MCV4疫苗的安全性是否因免疫状态而异; 评价在CD4%<15%的受试者中，2剂MCV4是否可产生免疫原性应答（定义为血清杀菌抗体滴度增加4倍或更多，达到至少1：8）; 确定可能影响MCV4应答的宿主免疫遗传决定因素。

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. The recent approval by the FDA of the quadrivalent meningococcal conjugate vaccine (MCV4) has led to a recommendation to vaccinate 11-12 year-old individuals at a pre-adolescent visit, individuals entering high school (approximately 15 years of age) and incoming college freshman living in dormitories, in recognition of the increased meningococcal disease risk during adolescence. As the majority of children with perinatally acquired HIV infection have aged into adolescence, and the majority of new pediatric HIV infections in the US are occurring in the adolescent age group, the new age-based recommendations for meningococcal immunization patients will lead to most HIV-infected youth being age-eligible for a vaccine for which there are no safety or immunogenicity data available from HIV-infected populations. This phase I/II study will evaluate the safety and immunogenicity of MCV-4 in 296 HIV-infected youth between \u8805?11 and <25 years of age. This study is also designed to answer several important questions related to immunization of HIV-infected youth including both short-term and long-term immunogenicity. The primary objectives are: To compare the immunogenicity of the MCV4 in HIV-1 infected youth at 28 weeks between a single-dose regimen vs. a two-dose regimen, where an immunogenic response is defined as a 4-fold or greater increase in serum bactericidal antibody titers; To estimate the short-term (4 and 24 weeks) immunogenicity of the MCV4 vaccine in HIV-1 infected youth for those in Group 1 (CD4% \ul >\ulnone 15); To estimate the long-term (at 72 weeks) immunogenicity of the MCV4 vaccine in HIV-1 infected youth; To evaluate the safety of the MCV4 vaccine in HIV-1 infected youth, including short-term local and systemic reactions following administration of the vaccine. HYPOTHESIS MCV-4 immunization in HIV-infected youth will be safe and the vaccine will be immunogenic in a single dose regimen for youth who have CD4% >\ but two doses will be required for immunogenicity in youth who have CD4%<15. SPECIFIC AIMS To compare the immunogenicity of the quadrivalent meningococcal conjugate vaccine (MCV4) in HIV-1 infected youth at 28 weeks between a single-dose regimen vs. a two-dose regimen, where an immunogenic response is defined as a 4-fold or greater increase in serum bactericidal antibody titers; To estimate the short-term (4 and 24 weeks) immunogenicity of the MCV4 vaccine in HIV-1 infected youth for those in Group 1 (CD4% \ul >\ulnone 15); To estimate the long-term (at 72 weeks) immunogenicity of the MCV4 vaccine in HIV-1 infected youth; To evaluate the safety of the MCV4 vaccine in HIV-1 infected youth, including short-term local and systemic reactions following administration of the vaccine. To examine whether the short and long-term immunogenicity of the MCV4 in HIV-1 infected youth varies as a function of the study subjects' immune status at the time of vaccination; To compare the long-term immunogenicity (at 72 weeks) of the MCV4 in HIV-1 infected youth between a 1-dose vs. 2-dose regimen for those in Group 1 (CD4% \ul >\ulnone 15) To evaluate whether the safety of the MCV4 vaccine varies by immune status based on CD4% at the time of vaccination; To evaluate whether, in subjects with CD4% < 15%, 2 doses of MCV4 can produce an immunogenic response (defined as a 4-fold or greater increase \cf0 in serum bactericidal antibody titers\cf2 reaching at least 1:8); To identify host genetic determinants of immunity that may affect\b \b0 the response to MCV4.