Passive-Active Immunization Strategies Against Pediatric AIDS

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和艾滋病的儿童出生的艾滋病毒感染的妇女人数迅速增加，在整个发展中国家。任何预防儿童艾滋病的疫苗都必须在出生时安全接种，并且必须在母体存在抗病毒抗体的情况下迅速引发病毒特异性免疫，以防止出生后通过母乳喂养多次接触艾滋病毒。目前正在成人中进行评估的艾滋病毒疫苗似乎诱导免疫的速度太慢，无法预防产后艾滋病毒传播或儿科艾滋病。因此，研究人类婴儿中HIV免疫原的免疫原性和有效性对于开发HIV疫苗以预防儿科艾滋病至关重要;然而，此类研究在技术上要求极高，在伦理上具有挑战性。我们提出的项目将使用SIV/新生儿恒河猴模型的儿科艾滋病毒/艾滋病，以评估候选灵长类慢病毒疫苗在新生儿和婴儿灵长类动物的免疫原性和有效性;该模型是唯一适合于提供所需的信息，以开发疫苗垂直艾滋病毒传播和儿科艾滋病。为了确定由两种减毒的重组痘病毒基SIV疫苗（MVA-SIVgpe和ALVAC-SIVgpe）引起的宿主防御应答，其是保护幼年恒河猴抵抗多次低剂量口服SIV攻击（在4周龄时）所必需的，我们将： 1)评价被动转移用痘病毒SIV疫苗免疫的成年猕猴的超免疫血清是否可以保护幼年猕猴在口服SIV暴露后免受感染或疾病。 2)确定出生时给予猕猴的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迅速引发针对口服SIV感染或疾病的保护性免疫。 3)通过在口服SIV攻毒前选择性耗竭接种动物中的细胞（使用单克隆抗体），确定特定免疫细胞群（即CD 8+细胞、NK细胞）是否是疫苗介导的保护幼猴抵抗口服SIV所必需或足够的。

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.