Recombinant Sendai Virus as a Novel HIV Vaccine Vector

描述（由申请方提供）：本项目的长期目标是制备和表征有效的HIV活病毒候选疫苗。成功的HIV疫苗应易于生产和施用，并应引发有效和持久的B和T细胞应答。鼠1型副流感病毒（Sendal病毒; SV）是副粘病毒家族的成员，可通过反向遗传学操作以递送HIV包膜糖蛋白。根据我们目前的人体试验的初步结果，该鼠病毒可能被证明是一种极好的疫苗载体，这些试验检查了SV作为人副流感病毒1型疫苗的作用，并且我们的研究表明鼻内SV和SV重组体（rSV）具有强效免疫原性。我们进一步表明，鼻内注射SV疫苗将被证明是一种简单有效的方法，可以引发针对HIV的全身和粘膜免疫应答。在这一重点申请中，我们提出了以下两个目标，以满足我们表征基于SV的HIV疫苗的免疫潜力的目标： 目的1：研究鼻内注射表达HIV包膜蛋白的重组SV（rSV-env）诱导的粘膜和全身B细胞反应。目的2：研究rSV-env经鼻给药后诱导的CD 4+和CD 8 + T细胞反应。预期作为活病毒疫苗，rSV-env将引起强烈且持久的B和T细胞应答，将在两个特定目标中进行评价。预测该疫苗载体成功的rSV的独特属性包括在卵中将rSV扩增至巨大滴度的能力（FDA批准的用于人疫苗的培养系统）、易于通过鼻内途径施用（避免了对无菌注射器和针头的需要以及能够诱导粘膜伊加的途径）以及引发有效和稳定的B和T细胞应答的能力。本申请中描述的研究可能最终将rSV鉴定为可用于预防HIV的有效鼻内疫苗媒介物。

DESCRIPTION (provided by applicant): The long-term objective of this project is to prepare and characterize an effective, live virus vaccine candidate for HIV. A successful HIV vaccine should be easily produced, administered and should trigger potent and durable B and T cell responses. The murine parainfluenza type 1 virus (Sendal virus; SV) is a member of the Paramyxovirus family which can be manipulated through reverse genetics to deliver HIV envelope glycoproteins. This murine virus is likely to prove an excellent vaccine vector based on preliminary results from our current human trials examining SV as a vaccine for human parainfluenza virus type 1 and our studies indicating the potent immunogenicity of intranasal SV and SV recombinants (rSV). We further suggest that intranasal administration of SV-based vaccines will prove to be a facile and effective means of priming systemic and mucosal immune responses against HIV. In this focused application we propose the following two aims to meet our objectives of characterizing the immune potential of SV-based HIV vaccines: Aim 1: To examine mucosal and systemic B cell responses elicited by intransasal recombinant SV expressing HIV envelope protein (rSV-env). Aim 2: To examine CD4 + and CD8 + T cell responses elicited by intransasal rSV-env. It is expected that as a live virus vaccine, rSV-env will elicit strong and durable B and T cell responses, to be evaluated in the two specific aims. Unique attributes of rSV which predict the success of this vaccine vector include the capacity to expand rSV to enormous titer in eggs (an FDA-approved culture system for human vaccines), easy administration by the intranasal route (obviating requirement for sterile syringes and needles and a route capable of inducing mucosal IgA) and the capacity to elicit potent and stable B and T cell responses. Studies described in this application may ultimately identify rSV as an effective intranasal vaccine vehicle useful in the prevention of HIV.