Recombinant Sendai Virus as a Novel HIV Vaccine Vector

描述（由申请人提供）：该项目的长期目标是制备和表征一种有效的HIV候选活病毒疫苗。一种成功的艾滋病毒疫苗应易于生产和施用，并应引发有效和持久的B细胞和T细胞反应。鼠副流感1型病毒（森达尔病毒；SV）是副粘病毒家族的一员，可通过反向遗传学操纵其传递HIV包膜糖蛋白。基于我们目前对SV作为人类1型副流感病毒疫苗的人体试验的初步结果，以及我们的研究表明鼻内SV和SV重组体（rSV）具有强大的免疫原性，这种小鼠病毒很可能被证明是一种优秀的疫苗载体。我们进一步建议，鼻内注射基于sv的疫苗将被证明是一种简单有效的启动针对HIV的全身和粘膜免疫反应的手段。在这一重点应用中，我们提出以下两个目标，以实现我们描述基于sv的艾滋病毒疫苗的免疫潜力的目标：

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.