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）：迫切需要一种疫苗，以防止艾滋病毒传播并帮助整个发展中国家迅速增加的HIV感染妇女所生的儿童。任何防止儿童辅助的疫苗都必须在出生时安全，并且必须在存在母体抗病毒药抗体的情况下迅速引起病毒特异性免疫，以防止通过乳房喂养产后多种产后对HIV的暴露。目前在成年人中评估的HIV疫苗似乎太慢，无法防止产后HIV传播或小儿艾滋病。因此，研究HIV免疫原性在人类婴儿中的免疫原性和功效对于开发HIV疫苗以防止小儿艾滋病至关重要。但是，这样的研究在技术上苛刻，在道德上具有挑战性。我们提出的项目将使用小儿艾滋病毒/艾滋病的SIV/新生儿恒河猴模型来评估新生儿和婴儿灵长类动物中候选灵长类动物慢病毒疫苗的免疫原性和功效。该模型非常适合提供针对垂直艾滋病毒传播和小儿艾滋病开发疫苗所需的信息。确定由两种衰减的，重组痘病毒基于SIV疫苗（MVA-SIVGPE和ALVAC-SIVGPE）引起的宿主防御反应，这些反应是保护婴儿恒河猕猴免受多种，低剂量的口服SIV挑战（4周）所必需的必要的。 1）评估用基于痘病毒的SIV疫苗免疫的成年猕猴的高免疫血清是否可以保护婴儿猕猴在口腔SIV暴露后免受感染或疾病。 2）确定在出生时给猕猴施用的SIV - 可控病毒疫苗方案是否可以在患有或缺乏被动获得的SIV和痘病毒特异性抗体的婴儿中迅速对口腔SIV感染或疾病产生保护性免疫。 3）确定特定的免疫细胞群（即CD8+细胞，NK细胞）是否需要或足以通过在口服SIV挑战之前选择性地耗尽疫苗的动物中疫苗的细胞（具有单克隆抗体）来选择疫苗介导的婴儿猕猴对口服SIV的保护。