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.
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