DEVELOPMENT OF AN HIV-1 AND HTLV-1 VACCINE IN ANIMAL MODELS

在动物模型中开发 HIV-1 和 HTLV-1 疫苗

• 批准号: 2463673
• 负责人: Genoveffa Franchini
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2463673
• 关键词: AIDS vaccines; HIV infections; Macaca mulatta; Pan; active immunization; attenuated microorganism; baboons; disease /disorder model; drug design /synthesis /production; human T cell lymphotropic virus type 1; human immunodeficiency virus 1; human immunodeficiency virus 2; interleukin 12; interleukin 2; laboratory rabbit; longitudinal animal study; molecular biology; nonhuman therapy evaluation; simian immunodeficiency virus; simian virus; vaccine development; viral vaccines; virus antigen; virus genetics

Efforts in the development of poxvirus-based vaccines to prevent HIV-I and HTLV-I infection are continuing. SIV model: A protocol designed to obtain preclinical data in the pathogenic SIV251 macaque model is ongoing. The protocol was designed to investigate the modulatory effect of interleukins such as interleukines 2 (IL-2) and 12 (IL-12) on the immunogenicity of NYVAC SIV gag, pol, and env vaccines The adjuvant effect of NYVAC-IL-2 and NYVAC-IL-12, at the time of immunization, was evidenced by a change in the vaccinees of the systemic immune response against viral antigens. Higher cellular immune responses, at the expenses of humoral immune responses, were measured in animals exposed to IL-12 at the time of immunization. Live SIV251 challenge was performed intravenously in half of the animals and intrarectally in the remaining half. Fifty percent of the animals in both groups were able to control acute viral infection. The immunological modulation induced by IL-2 and IL-12, however, did not correlate with the ability of the animals to control the acute viremia. The effect of these vaccine regimens in the clinical course of SIV infection remains to be investigated. Chimpanzee model: One year ago we started a protocol designed to compare the immunogenicity and efficacy of NYVAC and ALVAC HIV vaccines in chimpanzees. The animals have been immunized four times with recombinant poxvirus vectors carrying the gag, pol, env, and nef genes. The plan is to challenge these animals intrarectally with the chimpanzee-adapted HIV-IC499 isolate, which is being tested now for infectivity. HTLV-I in rabbits: Immunization and challenge experiments with NYVAC HTLV-I vaccines are aimed at defining the importance of various viral antigens as components of a vaccine formulation and the vaccination regimens. STLV-I in primates: At the Southwest Foundation a high prevalence of STLV-I infection and the development of T-cell lymphoma-infected baboons have been described. A collaborative effort has been initiated to eradicate STLV-I from this colony by vaccinating young baboons. Studies on the incidence of STLV-I infection in adults and maternal-fetal transmission have been initiated to define the cohort of animals to be vaccinated in a preliminary study. The advantage of the primate model is the possibility of testing vaccine efficacy in a natural setting of STLV-I transmission.

开发痘病毒疫苗预防艾滋病毒I型的努力 和HTLV-I感染仍在继续 SIV模型：旨在获得临床前数据的方案， 致病性SIV 251猕猴模型正在进行中。 设计试验方案 研究白细胞介素的调节作用， 白细胞介素2（IL-2）和12（IL-12）对NYVAC免疫原性的影响 SIV gag、pol和env疫苗 在免疫时，NYVAC-IL-12的表达通过以下变化来证明： 接种者对病毒抗原的全身免疫反应。 更高的细胞免疫应答，以体液免疫为代价 在暴露于IL-12的动物中，在 次免疫 静脉内进行活SIV 251攻击， 一半的动物和直肠内在剩下的一半。 五十 两组动物中均有%的动物能够控制急性病毒感染， 感染 IL-2和IL-12诱导的免疫调节， 然而，与动物的控制能力无关， 急性病毒血症 这些疫苗方案在 SIV感染的临床过程仍有待研究。 黑猩猩模型：一年前，我们开始了一项协议， 比较NYVAC和ALVAC HIV疫苗的免疫原性和有效性 在黑猩猩身上。 动物已经免疫四次， 携带gag、pol、env和nef基因的重组痘病毒载体。 该计划是在这些动物的直肠内用 黑猩猩适应的HIV-IC499分离株，目前正在测试 传染性 兔中的HTLV-I：NYVAC免疫和攻毒实验 HTLV-I疫苗旨在确定各种病毒的重要性， 作为疫苗制剂组分的抗原和疫苗接种 养生法 灵长类动物中的STLV-I：在西南基金会， STLV-I感染和T细胞淋巴瘤感染的发展 狒狒被描述过。 一项合作努力已经启动 通过给小狒狒接种疫苗来根除STLV-I 成人STLV-I感染发病率的研究 已经启动了母胎传播来定义队列 在一项初步研究中， 的优点 灵长类动物模型是测试疫苗效力的可能性， STLV-I变速器的自然设置。