Risk of Neonatal Vaccination for HIV/SIV Exposed Infants

HIV/SIV 暴露婴儿的新生儿疫苗接种风险

• 批准号: 8467562
• 负责人: Donald L Sodora
• 金额: $ 88.95万
• 依托单位: SEATTLE BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-18 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8467562
• 关键词: Address; Age; Animal Model; Anti-Retroviral Agents; BCG Vaccine; Birth; Blood Cells; Blood Circulation; Bottle feeding; Breast Feeding; CD4 Positive T Lymphocytes; Calmette-Guerin Bacillus; Cells; Cesarean section; Child; Collaborations; Communities; Dependence; Developed Countries; Developing Countries; Development; Future; Goals; HIV; HIV Infections; HIV vaccine; Health; Human; Human Milk; Immune; Immune response; Immunization; Immunologics; Immunology; Individual; Infant; Infant Health; Infection; Investigation; Laboratories; Life; Macaca; Macaca mulatta; Mediating; Modeling; Modern Medicine; Mothers; Mucous Membrane; NIH Program Announcements; National Institute of Dental and Craniofacial Research; Neonatal; Newborn Infant; Oral; Oral mucous membrane structure; Poliomyelitis; Population; Postpartum Period; Predisposition; Primates; Research; Resources; Risk; Role; SIV; SIV Vaccines; Safety; South Africa; Testing; Tonsil; Treatment Protocols; Tuberculosis; Vaccination; Vaccines; Vertical Disease Transmission; Washington; Water Pollution; Woman; adaptive immunity; clinical practice; cost effective; design; effective intervention; experience; feeding; immune activation; immunoregulation; insight; macrophage; oral HIV; pathogen; patient population; pregnant; prevent; programs; response; transmission process; vaccination schedule; vaccine development

DESCRIPTION (provided by applicant): Vaccinations are the most successful and cost-effective interventions in modern medicine. An HIV vaccine could save millions of lives and would be the centerpiece of HIV eradication efforts. However, numerous challenges remain in developing a vaccine that shows substantial efficacy in humans. Infants are one group likely to benefit from vaccine protection by preventing the nearly 400,000 new Mother-to-child transmissions (MTCT) of HIV worldwide each year. Access to anti-retroviral treatment (ART) has dramatically reduced MTCT in developed countries; however postpartum HIV transmission persists at unacceptably high levels in resource-poor settings. The reasons for this include: formula feeding not being affordable or safe (water contamination), lack of compliance to taking the ART, benefits of breastfeeding for the health of the infant and access of ART to all pregnant HIV-infected woman and their babies. In South Africa (where we have an ongoing study to assess impact of BCG vaccination in infants), and many other developing countries, the two vaccines given at birth are Bacillus Calmette-Guerin (BCG) and Oral Polio Vaccine (OPV). While these vaccines have clear protective benefits against disseminated tuberculosis and polio infection, there is also a potential downside. The very immune activation that elicits these beneficial responses may simultaneously increase an infant's susceptibility to HIV. Sub-analyses from the STEP as well as subsequent macaque SIV vaccine studies have implicated specific vaccine-induced immune responses in promoting HIV infection in vaccine recipients. If vaccines with anti-HIV/SIV activity can enhance HIV/SIV susceptibility, it is critical to assess if current immunization strategies can impact HIV transmission in HIV-exposed infants. The goals of this proposal are to: 1) Assess the immunologic impact of administration of BCG and OPV vaccines on HIV/SIV target cell recruitment and activation in infant rhesus macaques, and 2) Define the mechanism of BCG/OPV-mediated immune modulation through ex-vivo stimulation of macaque and human cells. This proposal will test the hypothesis that early administration (within days of birth) of the neonatally-administered vaccines BCG/OPV increases the risk of oral SIV acquisition in infants. To address this hypothesis, the Sodora laboratory will draw on our extensive experience in innate immunology and macaque models of SIV-infection while collaborating with Dr. Deborah Fuller, an expert in vaccination studies and adaptive immunity, to develop a thorough understanding of BCG/OPV-induced immune responses. This proposal will define the impact of neonatal vaccinations on recruitment and activation of HIV/SIV target cells as well as SIV transmission, to provide insights into the role of BCG/OPV neonatal vaccinations on oral MTCT SIV/HIV transmission. The investigation of vaccines currently administered to HIV-exposed infants makes these studies particularly relevant for current clinical practice while also facilitating the development of an effective HIV vaccine with optimal safety for HIV-exposed individuals.

描述（由申请人提供）：接种疫苗是现代医学中最成功，最具成本效益的干预措施。艾滋病毒疫苗可以挽救数百万的生命，这将是消除艾滋病毒的核心。然而，开发一种疫苗，在人类中表现出重大疗效的疫苗仍存在许多挑战。婴儿是每年在全球范围内近40万个新的HIV母亲传播（MTCT），这是一个可能从疫苗保护中受益的一组。在发达国家，获得抗逆转录病毒治疗（ART）已大大降低了MTCT；但是，产后艾滋病毒的传播在资源贫乏的设置中持续不可接受。其原因包括：配方奶粉不承受能力或安全（水污染），缺乏遵守艺术的依从性，母乳喂养对婴儿健康的好处以及对所有怀孕的HIV感染的艾滋病毒感染的妇女及其婴儿的使用。在南非（我们正在进行的研究以评估婴儿中BCG疫苗接种的影响）以及许多其他发展中国家，出生时给出的两种疫苗是Calmette-Guerin（BCG）和口服脊髓灰质炎疫苗（OPV）。尽管这些疫苗对分布结核和脊髓灰质炎感染具有明显的保护益处，但仍有潜在的缺点。引起这些有益反应的非常免疫激活可能会同时增加婴儿对艾滋病毒的敏感性。从该步骤以及随后的猕猴SIV疫苗研究中进行的亚肛门物已暗示特定疫苗诱导的免疫反应在促进疫苗受体中的HIV感染中。如果具有抗HIV/SIV活性的疫苗可以增强HIV/SIV的易感性，那么评估是否至关重要 当前的免疫策略会影响艾滋病毒暴露婴儿的艾滋病毒传播。该提案的目标是：1）评估BCG和OPV疫苗给药对婴儿猕猴的HIV/SIV靶细胞募集和激活的免疫学影响，以及2）定义BCG/OPV介导的免疫调节机制，通过猕猴和人类细胞的刺激刺激。该提案将检验以下假设：新生儿疫苗BCG/OPV的早期给药（在出生的几天之内）增加了婴儿口服SIV的风险。为了解决这一假设，Sodora实验室将利用我们在SIV感染的先天免疫学和猕猴模型中的丰富经验，同时与疫苗接种研究和适应性免疫专家Deborah Fuller博士合作，以对BCG/OPV诱导的免疫反应进行彻底的了解。该提案将定义新生儿疫苗接种对HIV/SIV靶细胞的募集和激活以及SIV传播的影响，以洞悉BCG/OPV新生儿疫苗接种对口服MTCT SIV/HIV传播的作用。对当前对艾滋病毒暴露婴儿的疫苗进行的研究使这些研究与当前的临床实践特别相关，同时还促进了有效的HIV疫苗的开发，对艾滋病毒暴露的个体具有最佳的安全性。