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A heterologous prime-boosting strategy with replicating Vaccinia virus vectors and plant-produced HIV-1 Gag/dgp41 virus-like particles.

A heterologous prime-boosting strategy with replicating Vaccinia virus vectors and plant-produced HIV-1 Gag/dgp41 virus-like particles.
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Meador LR, Kessans SA, Kilbourne J, Kibler KV, Pantaleo G, Roderiguez ME, Blattman JN, Jacobs BL, Mor TS,


Meador LR, Kessans SA, Kilbourne J, Kibler KV, Pantaleo G, Roderiguez ME, Blattman JN, Jacobs BL, Mor TS, (click to view)

Meador LR, Kessans SA, Kilbourne J, Kibler KV, Pantaleo G, Roderiguez ME, Blattman JN, Jacobs BL, Mor TS,

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Virology 2017 04 28507() 242-256 pii 10.1016/j.virol.2017.04.008

Abstract

Showing modest efficacy, the RV144 HIV-1 vaccine clinical trial utilized a non-replicating canarypox viral vector and a soluble gp120 protein boost. Here we built upon the RV144 strategy by developing a novel combination of a replicating, but highly-attenuated Vaccinia virus vector, NYVAC-KC, and plant-produced HIV-1 virus-like particles (VLPs). Both components contained the full-length Gag and a membrane anchored truncated gp41 presenting the membrane proximal external region with its conserved broadly neutralizing epitopes in the pre-fusion conformation. We tested different prime/boost combinations of these components in mice and showed that the group primed with NYVAC-KC and boosted with both the viral vectors and plant-produced VLPs have the most robust Gag-specific CD8 T cell responses, at 12.7% of CD8 T cells expressing IFN-γ in response to stimulation with five Gag epitopes. The same immunization group elicited the best systemic and mucosal antibody responses to Gag and dgp41 with a bias towards IgG1.

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