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

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.

An Alternative Perfusion Approach for the Intensification of Virus-Like Particle Production in HEK293 Cultures

“…The use of Gag to generate virus-like particles (VLPs) has become a promising option to develop alternative platforms for recombinant vaccines being able to target several diseases (Lua et al, 2014;Cervera et al, 2019). Having multimeric structures such as Gag-VLPs helps induce a stronger immune response (Meador, 2017) and since they are produced by a budding process, the lipid envelope can be further used for particle pseudotyping (Kueng et al, 2007(Kueng et al, , 2011Sharma et al, 2017). The addition of conjugated antigens can be used to target different diseases, such as influenza (Venereo-Sanchez et al, 2017).…”

The potential of plant systems to break the HIV‐TB link

“…Plant-derived vaccines are suitable for booster vaccines, specifically where the number of doses is needed over long periods to induce and maintain immunity, in population where reinfection occurs due to environmental exposure. Proof-of-concept reports described in mice have indicated the efficient use of plants cell in heterologous prime-boost strategies (Daniell, 2019;Daniell et al, 2018;Lakshmi et al, 2013;Meador et al, 2017). However, in the absence of such priming, plant cells are not suitable for vaccination against infectious diseases (Chan et al, 2016;Daniell, 2019;Xiao and Daniell, 2017).…”