Vaccine-induced HIV antibody responses in infants

婴儿中疫苗诱导的艾滋病毒抗体反应

基本信息

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
项目类别：
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

项目摘要

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预防了艾滋病毒母婴传播，但儿童艾滋病毒感染仍然是一个主要的公共卫生问题。根据联合国艾滋病规划署 2010 年报告，2009 年有超过 350,000 名婴儿感染艾滋病毒。几乎一半的婴儿艾滋病毒感染是由母乳喂养造成的。因此，迫切需要开发一种疫苗来预防产后感染艾滋病毒。由于新生儿免疫系统对有效疫苗接种提出了特定的挑战，目前尚不清楚成人 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。最近完成的金丝雀痘原蛋白增强 RV144 试验在成人中观察到 31% 的适度保护，为 HIV 疫苗研究领域带来了有效阻断传播疫苗的新希望。事实上，疫苗引发的针对 HIV 包膜 (Env) V1V2 区域的非中和抗体反应与观察到的保护作用相关。这项研究提供了一个基准，可以比较所有以前和未来的疫苗试验。儿科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 HIV 暴露婴儿中的两种 gp120 疫苗，PACTG 326 评估了与 RV144 类似的金丝雀痘引发剂、gp120 蛋白加强策略。婴儿疫苗诱导了艾滋病毒特异性抗体，但这些抗体的特异性和功能尚未得到表征。有趣的是，用广泛中和单克隆抗体被动免疫的新生猕猴在受到猿猴-人类免疫缺陷病毒攻击后比未经治疗的受到攻击的新生儿具有更有效的功能反应。这一结果表明，母体获得的抗体会影响 HIV 暴露婴儿接种疫苗后的 HIV 特异性抗体功能反应。我们建议研究来自 PACTG 230 和 326 婴儿疫苗试验的 HIV 暴露、接种疫苗的婴儿中 HIV 特异性抗体的表位和类别特异性，以及中和和非中和功能。将婴儿的抗体反应与接受中等保护性 RV144 疫苗的成人抗体反应进行比较，以确定这些婴儿疫苗方案是否可能引发类似的保护性反应，例如 V1V2 特异性 IgG 反应。这项研究将为成人和暴露于 HIV 的婴儿 Env 疫苗引起的反应的差异提供重要的新见解，这些信息对于基于已被证明对成人具有保护作用的疫苗制定婴儿 HIV 疫苗策略至关重要。公共卫生相关性：每年有超过 300,000 例感染，儿童艾滋病毒仍然是一个重大的公共卫生问题，迫切需要开发一种有效的疫苗。然而，由于婴儿免疫系统不成熟，目前尚不清楚成人开发的艾滋病毒疫苗策略是否适用于婴儿疫苗接种。本研究的目标是研究在 HIV 暴露婴儿中疫苗诱导的 HIV 特异性抗体反应的精细特异性和功能，并将婴儿反应与中等保护性 R144 HIV 疫苗试验中接种疫苗的成人的反应进行比较。确定婴儿 HIV 疫苗接种是否引起与适度保护的成人 HIV 疫苗相似的抗体反应是婴儿 HIV 疫苗设计的合理下一步。