Passive-Active Immunization Strategies Against Pediatric AIDS

针对儿童艾滋病的被动-主动免疫策略

基本信息

批准号：
7191649
负责人：
Marta L Marthas
金额：
$ 60.41万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-03-01 至 2009-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7191649
关键词：
AIDS/HIV problem Acquired Immunodeficiency Syndrome Active Immunization Adult African Age Animals Anti-Inflammatory Agents Antibodies Antibody Formation Antigens Antiviral Agents Attenuated B-Lymphocytes Biological Assay Birth Blood Breast Feeding CD8-Positive T-Lymphocytes Cells Child Childhood Clinical Control Groups Data Dendritic Cells Disease Dose Effectiveness End Point Euthanasia Exposure to Generations Genital system Goals Growth HIV HIV Infections HIV vaccine Hepatitis B Vaccines Hepatitis B Virus Host Defense Human Human Milk Human poliovirus Immune Immune Sera Immune response Immunity Immunization Immunization Schedule Immunologic Deficiency Syndromes Immunology Infant Infection Infection prevention Inflammatory Licensing Life Lymphoid Lymphoid Tissue MS4A1 gene Macaca Macaca mulatta Malaria Vaccines Measures Mediating Milk Modeling Monoclonal Antibodies Mucous Membrane Natural Killer Cells Neonatal Newborn Infant Numbers Oral Oral cavity Parasites Pathogenesis Phase Phenotype Physiology Plasma Polioviruses Population Poxviridae Primates Principal Investigator Publishing RNA Rate Recombinants Reporting Research Personnel Risk SIV SIV Vaccines Sexual Transmission Systemic infection T memory cell T-Lymphocyte Testing Time Tissues Treatment Protocols Tuberculosis Vaccinated Vaccination Vaccine Antigen Vaccine Design Vaccines Vaccinia Vesicular stomatitis Indiana virus Viral Viral Antibodies Viral Vaccines Viral Vector Viremia Virus Week Woman antibody-dependent cell cytotoxicity base clinical efficacy cytokine day defense response doxorubicin/mitomycin/vinblastine protocol immunogenic immunogenicity improved in vivo infancy insight neonate oral HIV oral vaccine pediatric AIDS peripheral blood postnatal prevent programs protective effect response success therapy design time interval transmission process tumor necrosis factor-alpha inhibitor vaccine efficacy vector viral RNA

项目摘要

DESCRIPTION (provided by applicant): A vaccine is urgently needed to prevent HIV transmission and AIDS in children born to the rapidly increasing number of HIV-infected women throughout the developing world. Any vaccine to prevent AIDS in children must be safe to give at birth and must rapidly elicit virus-specific immunity in the presence of maternal antiviral antibodies to protect against the multiple postnatal exposures to HIV through breast feeding. HIV vaccines currently being evaluated in adults appear to elicit immunity too slowly to prevent postnatal HIV transmission or pediatric AIDS. Thus, studies of the immunogenicity and efficacy of HIV immunogens in human infants are essential to developing an HIV vaccine to prevent pediatric AIDS; however, such studies are extremely technically demanding and ethically challenging. Our proposed project will use the SIV/neonatal rhesus model of pediatric HIV/AIDS to evaluate immunogenicity and efficacy of candidate primate lentiviral vaccines in newborn and infant primates; this model is uniquely suited to provide information needed to develop vaccines against vertical HIV transmission and pediatric AIDS. To determine the host defense responses elicited by two attenuated, recombinant poxvirus-based SIV vaccines (MVA-SIVgpe and ALVAC-SIVgpe) that are necessary to protect infant rhesus macaques against multiple, low dose oral SIV challenge (at 4 weeks of age) we will: 1) Evaluate whether passive transfer of hyper-immune serum from adult macaques immunized with poxvirus-based SIV vaccines can protect infant macaques against infection or disease after oral SIV exposure. 2) Determine whether an SIV-poxvirus vaccine regimen administered to macaques at birth can elicit protective immunity against oral SIV infection or disease rapidly in infants who have, or who lack, passively-acquired SIV- and poxvirus-specific antibodies. 3) Determine if specific immune cell populations (i.e. CD8+ cells, NK cells) are necessary or sufficient for vaccine-mediated protection of infant macaques against oral SIV by selectively depleting cells (with monoclonal antibodies) in vaccinated animals before oral SIV challenge.

描述（由申请人提供）：发展中国家迫切需要一种疫苗来预防艾滋病毒传播和儿童感染艾滋病，而这些儿童的数量迅速增加，感染艾滋病毒的妇女数量迅速增加。任何预防儿童艾滋病的疫苗都必须在出生时安全接种，并且必须在母体抗病毒抗体存在的情况下迅速引发病毒特异性免疫力，以防止产后通过母乳喂养多次接触艾滋病毒。目前正在成人中评估的艾滋病毒疫苗似乎引发免疫力的速度太慢，无法预防产后艾滋病毒传播或儿童艾滋病。因此，研究人类婴儿中艾滋病毒免疫原的免疫原性和功效对于开发预防儿童艾滋病的艾滋病毒疫苗至关重要；然而，此类研究在技术上要求极高，在伦理上也具有挑战性。我们提出的项目将使用儿科艾滋病毒/艾滋病的SIV/新生儿恒河猴模型来评估候选灵长类慢病毒疫苗在新生儿和幼年灵长类动物中的免疫原性和功效；该模型特别适合提供开发针对艾滋病毒垂直传播和儿童艾滋病的疫苗所需的信息。为了确定两种减毒重组痘病毒 SIV 疫苗（MVA-SIVgpe 和 ALVAC-SIVgpe）引起的宿主防御反应，这两种疫苗对于保护幼年恒河猴免受多次、低剂量口服 SIV 攻击（4 周龄）是必需的，我们将要： 1) 评估从接种基于痘病毒的 SIV 疫苗免疫的成年猕猴中被动转移超免疫血清是否可以保护幼猴在口服 SIV 暴露后免受感染或疾病。 2) 确定在猕猴出生时给予 SIV 痘病毒疫苗方案是否可以在具有或缺乏被动获得的 SIV 和痘病毒特异性抗体的婴儿中快速引发针对口腔 SIV 感染或疾病的保护性免疫力。 3) 在口服 SIV 攻击之前，通过选择性地消耗已接种动物的细胞（使用单克隆抗体），确定特定的免疫细胞群（即 CD8+ 细胞、NK 细胞）对于疫苗介导的针对口服 SIV 的幼年猕猴的保护是否是必要或充分的。