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利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 FDA最近批准了四价脑膜炎球菌结合疫苗(MCV4)，考虑到青春期期间脑膜炎球菌疾病风险的增加，建议在青春期前探视时为11-12岁的人、进入高中(约15岁)的人和住在宿舍的大学新生接种疫苗。由于大多数患有围产期获得性艾滋病毒感染的儿童已经进入青春期，而美国大多数新的儿童艾滋病毒感染发生在青少年年龄组，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艾滋病毒感染青年有资格接种疫苗，而艾滋病毒感染人群没有获得安全性或免疫原性数据。这项I/II期研究将评估MCV-4在296名感染HIV的青年中的安全性和免疫原性。这项研究还旨在回答与艾滋病毒感染青年免疫有关的几个重要问题，包括短期和长期免疫原性。主要目标是：比较单剂方案和双剂方案在28周时MCV4在感染HIV-1青年中的免疫原性，其中免疫原性反应定义为血清杀菌抗体效价增加4倍或更多；估计MCV4疫苗在感染HIV-1青年中短期(4周和24周)的免疫原性；评估MCV4疫苗在感染HIV-1青年中的短期(4和24周)免疫原性；评估MCV4疫苗在HIV-1感染青年中的长期免疫原性(72周)；评估MCV4疫苗在感染HIV-1的青少年中的安全性，包括接种疫苗后的短期局部和全身反应。 假设 在感染艾滋病毒的青年中接种MCV-4将是安全的，疫苗将在单剂方案中对患有CD4%和15%的青年具有免疫原性，但对于患有CD4%和15%的青年将需要两剂免疫原性。 具体目标 比较四价脑膜炎球菌结合疫苗(MCV4)在28周时在感染HIV-1的青年中的免疫原性，即单剂方案和双剂方案，其中免疫原性反应定义为血清杀菌抗体效价增加4倍或更多； 评估MCV4疫苗在HIV-1感染青年中的短期(4周和24周)免疫原性，用于第1组(CD4%)； 评估MCV4疫苗在感染HIV-1的青少年中的长期(72周)免疫原性； 评估MCV4疫苗在感染HIV-1的青少年中的安全性，包括接种疫苗后的短期局部和全身反应。 研究在感染HIV-1的青少年中，MCV4的短期和长期免疫原性是否随研究对象接种疫苗时的免疫状态而变化； 比较第1组(CD4%)和第2组(CD4%)的MCV4在感染HIV-1的青年中的长期免疫原性(72周)。 评估MCV4疫苗的安全性是否因接种时的免疫状态不同而不同； 评估在CD4%和15%的受试者中，两剂MCV4是否能产生免疫原性应答(定义为血清杀菌抗体效价增加4倍或更多，达到至少1：8)； 确定可能影响对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.