Vaccine-induced HIV antibody responses in infants

婴儿中疫苗诱导的艾滋病毒抗体反应

• 批准号: 8409869
• 负责人: Sallie R. Permar
• 金额: $ 7.85万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8409869
• 关键词: AIDS Vaccines; AIDS clinical trial group; ALVAC; Acquired Immunodeficiency Syndrome; Activities of Daily Living; Adult; Anti-Retroviral Agents; Antibodies; Antibody Formation; Antibody Specificity; Avidity; Benchmarking; Biological Assay; Birth; Breast Feeding; Country; Disease; Enrollment; Epidemic; Epitopes; Future; Goals; Growth and Development function; HIV; HIV Antibodies; HIV Envelope Protein gp120; HIV Infections; HIV drug resistance; HIV vaccine; Heterosexuals; Immune; Immune response; Immune system; Immunoglobulin G; Income; Infant; Infant Development; Infant Mortality; Infection; Intervention; Low income; Macaca; Macaca mulatta; Maternal antibody; Monkeys; Neonatal; Perinatal; Population; Poxviridae; Pregnant Women; Prophylactic treatment; Proteins; Protocols documentation; Public Health; Regimen; Reporting; Risk; Specificity; Testing; Vaccinated; Vaccination; Vaccine Design; Vaccine Research; Vaccines; Vertical Disease Transmission; World Health Organization; base; design; feeding; infant outcome; insight; meetings; neonate; neutralizing monoclonal antibodies; pediatric AIDS; pediatric human immunodeficiency virus; pediatric human immunodeficiency virus infection; postnatal; prevent; prophylactic; respiratory; response; simian human immunodeficiency virus; success; transmission process; vaccine candidate; vaccine development; vector; AIDS Vaccines; AIDS clinical trial group; ALVAC; Acquired Immunodeficiency Syndrome; Activities of Daily Living; Adult; Anti-Retroviral Agents; Antibodies; Antibody Formation; Antibody Specificity; Avidity; Benchmarking; Biological Assay; Birth; Breast Feeding; Country; Disease; Enrollment; Epidemic; Epitopes; Future; Goals; Growth and Development function; HIV; HIV Antibodies; HIV Envelope Protein gp120; HIV Infections; HIV drug resistance; HIV vaccine; Heterosexuals; Immune; Immune response; Immune system; Immunoglobulin G; Income; Infant; Infant Development; Infant Mortality; Infection; Intervention; Low income; Macaca; Macaca mulatta; Maternal antibody; Monkeys; Neonatal; Perinatal; Population; Poxviridae; Pregnant Women; Prophylactic treatment; Proteins; Protocols documentation; Public Health; Regimen; Reporting; Risk; Specificity; Testing; Vaccinated; Vaccination; Vaccine Design; Vaccine Research; Vaccines; Vertical Disease Transmission; World Health Organization; base; design; feeding; infant outcome; insight; meetings; neonate; neutralizing monoclonal antibodies; pediatric AIDS; pediatric human immunodeficiency virus; pediatric human immunodeficiency virus infection; postnatal; prevent; prophylactic; respiratory; response; simian human immunodeficiency virus; success; transmission process; vaccine candidate; vaccine development; vector

DESCRIPTION (provided by applicant): Despite the success of antiretroviral interventions to prevent mother to child transmission of HIV, pediatric HIV infection continue to be a major pubic heath concern. According to the UNAIDS 2010 report, more than 350,000 infants were infected with HIV in 2009. Breastfeeding is responsible for almost half of infant HIV infections. Thus, there is an urgent need to develop a vaccine to prevent postnatal HIV acquisition. As the neonatal immune system presents specific challenges to effective vaccination, it is unclear if results of HIV vaccine studies in adults can predict the outcome of infant vaccination with similar vaccine regimens. The moderate 31 % protection observed in adults from the recently completed canarypox prime-protein boost RV144 trial has brought new hopes for an effective transmission-blocking vaccine to the HIV vaccine research field. In fact, vaccine -elicited nonneutralizing antibody responses against.the V1V2 region of the HIV Envelope (Env) have been associated with the observed protection. This study provides a benchmark by which all previous and future vaccine trials can be compared. The Pediatric AIDS Clinical Trial Group protocol (PACTG) 230 and 326 are two of the main pediatric HIV vaccine trials conducted to date. PACTG 230 assessed two gp120 vaccines in HIV-exposed infants and PACTG 326 evaluated a canarypox-prime, gp120 protein boost strategy similar to that to RV144. The infant vaccines induced HIV-specific antibodies, but the specificity and function of these antibodies have not been characterized. Interestingly, neonatal macaques passively immunized with a broadly neutralizing monoclonal antibody had more potent functional responses following challenge with a Simian-Human immunodeficiency virus than untreated, challenged neonates. This result indicates that maternally-acquired antibodies influence HIV-specific antibody functional responses following vaccination of HIV-exposed infants. We propose to investigate the epitope and class specificity, as well as the neutralizing and non-neutralizing functions of HIV-specific antibodies in HIV- exposed, vaccinated infants from PACTG 230 and 326 infant vaccine trials. The antibody responses in infants will be compared to those in adults who received the moderately-protective RV144 vaccine to determine whether a similar protective response, such as the V1V2-specific IgG response, may have been elicited by these infant vaccine regimens. This study will bring important new insights into the differences in the adult and HIV-exposed infant Env vaccine-elicited responses, information that is critical for the development of infant HIV vaccine strategies based on vaccines that are proven to be protective in adult populations. PUBLIC HEALTH RELEVANCE: With over 300,000 infections every year, pediatric HIV continues to be a major public health issue and there is an urgent need to develop an efficient vaccine. However, because the infant immune system is immature, it is unclear if HIV vaccine strategies developed in adults would be applicable to infant vaccination. The goal of this study is to investigate the fine specificity and function of vaccine-induced HIV-specific antibody responses in HIV-exposed infants, and compare infant responses to those of vaccinated adults from the moderately protective R144 HIV vaccine trial. Determining whether infant HIV vaccination elicited antibody responses similar to that of the moderately protective adult HIV vaccine is the logical next step in infant HIV vaccine design.

描述（由申请人提供）：尽管抗逆转录病毒干预措施成功地阻止母亲传播HIV，但小儿艾滋病毒感染仍然是主要的耻骨荒地。根据《 UNAIDS 2010》的报告，2009年感染了350,000多名婴儿。母乳喂养造成了几乎一半的婴儿艾滋病毒感染。因此，迫切需要开发一种疫苗以防止产后艾滋病毒的获取。由于新生儿免疫系统提出了有效疫苗接种的特定挑战，因此尚不清楚成人HIV疫苗研究的结果是否可以预测婴儿疫苗接种的结果 疫苗方案。来自最近完成的CanaryPox原蛋白增强RV144试验的成年人中观察到的中等31％的保护，给HIV疫苗研究领域带来了有效的传输阻滞疫苗的新希望。实际上，针对疫苗的非中和抗体反应对疫苗的非中和抗体反应。HIV包膜的V1V2区域已与观察到的保护有关。这项研究提供了一个基准，可以通过该基准比较所有以前和将来的疫苗试验。 小儿艾滋病临床试验组方案（PACTG）230和326是迄今为止进行的两项主要儿科HIV疫苗试验。 PACTG 230评估了暴露于HIV的婴儿和PACTG 326中的两种GP120疫苗，评估了类似于RV144的CanaryPox-Prime GP120蛋白增强策略。婴儿疫苗诱导HIV特异性抗体，但这些抗体的特异性和功能尚未表征。有趣的是，与未经治疗的，挑战的新生儿相比，用广泛中和的单克隆抗体被动免疫的新生儿猕猴具有更有效的功能反应。该结果表明，在疫苗接种HIV暴露的婴儿后，产妇获得的抗体会影响HIV特异性抗体功能反应。我们建议研究表位和类别的特异性，以及HIV特异性抗体的中和和非中和化功能在HIV暴露的，来自PACTG 230和326个婴儿疫苗试验的疫苗接种婴儿中。将将婴儿的抗体反应与接受中等保护RV144疫苗的成年人的抗体反应进行比较，以确定这些婴儿疫苗方案是否可能引起了类似的保护性反应（例如V1V2特异性IgG反应）。这项研究将为成年和艾滋病毒暴露于疫苗疫苗诱发的反应的差异带来重要的新见解，这对于基于疫苗的婴儿HIV疫苗策略至关重要的信息，这些疫苗在成人种群中被证明具有保护性。 公共卫生相关性：每年有30万多种感染，小儿艾滋病毒仍然是一个重大的公共卫生问题，迫切需要开发有效的疫苗。但是，由于婴儿免疫系统不成熟，尚不清楚成年人开发的HIV疫苗策略是否适用于婴儿疫苗接种。这项研究的目的是 为了研究疫苗诱导的艾滋病毒暴露婴儿HIV特异性抗体反应的良好特异性和功能，并比较了来自中等保护性R144 HIV疫苗试验的婴儿反应与接种疫苗的成年人的反应。确定婴儿HIV疫苗接种是否引起与适度保护性成人HIV疫苗相似的抗体反应是婴儿HIV疫苗设计的逻辑下一步。