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

作者：Meador Lydia R; Kessans Sarah A; Kilbourne Jacquelyn; Kibler Karen V; Pantaleo Giuseppe; Esteban Roderiguez Mariano; Blattman Joseph N; Jacobs Bertram L; Mor Tsafrir S

来源：Virology, 2017, 507: 242-256.

DOI：10.1016/j.virol.2017.04.008

• HIV-1
• Vaccinia virus
• Prime/boost
• Virus-like particles
• Tobacco mosaic virus
• Electron microscopy
• Live vector vaccines
• Subunit vaccines

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-gamma 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.

• 出版日期2017-7