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

努力开发以痘病毒为基础的疫苗以预防艾滋病毒-I HTLV-I感染仍在继续。 SIV模型：一种旨在获得临床前数据的方案 致病的SIV251猕猴模型正在进行中。该协议被设计成 为了研究白介素2的调节作用，如 IL-2和IL-12对NYVAC免疫原性的影响 SIV Gag、Pol和Env疫苗NYVAC-IL-2和 NYVAC-IL-12在免疫时的证据是 疫苗接种者对病毒抗原的全身免疫反应。 更高的细胞免疫应答，但以体液免疫为代价 在暴露于IL-12的动物中，测量了反应 免疫接种。实况SIV251挑战赛是在 一半的动物在直肠内，另一半在直肠内。五十 两组动物中都有百分比的动物能够控制急性病毒 感染。IL-2和IL-12诱导的免疫调节， 然而，与动物的控制能力并不相关 急性病毒血症。这些疫苗方案在儿童中的效果 SIV感染的临床病程仍有待调查。 黑猩猩模型：一年前，我们开始了一项旨在 NYVAC和ALVAC HIV疫苗的免疫原性和免疫效果比较 在黑猩猩身上。这些动物已经接种了四次疫苗 携带gag、pol、env和nef基因的重组痘病毒载体。 我们的计划是在直肠内挑战这些动物 黑猩猩适应的HIV-IC499分离株，目前正在测试 传染性。 兔HTLV-I免疫和NYVAC攻击实验 HTLV-I疫苗旨在确定各种病毒的重要性 作为疫苗配方成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的高流行率 STLV-I感染与T细胞淋巴瘤的发生发展 有人描述过狒狒。已经启动了一项合作努力 通过给年轻的狒狒接种疫苗来根除这个群体中的STLV-I。 成人和成人STLV-I感染发病率的研究 已经启动了母婴传播来确定队列 在一项初步研究中将对动物进行免疫接种。的优势 灵长类动物模型是测试疫苗效力的可能性 STLV-I传输的自然设置。

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.