Development of a porcine reproductive and respiratory syndrome virus-like-particle-based vaccine and evaluation of its immunogenicity in pigs

Abstract

Porcine reproductive and respiratory syndrome (PRRS) is a leading cause of economic burden to the pork industry worldwide. The routinely used modified live PRRS virus vaccine (PRRS-MLV) induces clinical protection, but it has safety concerns. Therefore, in an attempt to develop a safe and protective inactivated PRRSV vaccine, we generated PRRS-virus-like-particles (PRRS-VLPs) containing the viral surface proteins GP5-GP4-GP3-GP2a-M or GP5-M using a novel baculovirus expression system. Our in vitro results indicated that the desired PRRSV proteins were incorporated in both the VLPs preparations based on their reactivity in immunogold electron microscopy and ELISA. To boost their immunogenicity in pigs, we entrapped the PRRS-VLPs in PLGA nanoparticles and coadministered them intranasally with a potent adjuvant. We then evaluated their efficacy in pigs against a viral challenge using a virulent heterologous field isolate. Our results indicated that PRRS-VLPs induced an anamnestic immune response, since we observed boosted IgG and IFN-γ production in vaccinated and virus-challenged animals, but not during the pre-challenge period. Importantly, a two-log reduction in the lung viral load was detected in PRRS-VLP-vaccinated animals. In conclusion, we generated PRRS-VLPs containing up to five viral surface proteins and demonstrated their immunogenicity in pigs, but further studies are required to improve its immunogenicity and efficacy as a vaccine candidate.

Effector mechanisms of humoral immunity to porcine reproductive and respiratory syndrome virus

“…However, the impressive mutability and recombination capacity and, therefore, genetic variability, of the virus resulted in incomplete clinical benefit of live or inactivated PRRS vaccines [9, 10]. Recent efforts to develop alternative vaccination methods, such as virus-like particles, replicon vectors, and a nonpathogenic porcine circovirus type 1 virus vector to induce a neutralizing response against purported neutralizing epitopes have yet to demonstrate immunological protective efficacy [11–13]. …”

Intranasal immunization of pigs with porcine reproductive and respiratory syndrome virus-like particles plus 2′, 3′-cGAMP VacciGrade™ adjuvant exacerbates viremia after virus challenge

“…Therefore, these three proteins likely play important roles in the assembly of virus particles for PRRSV, although other minor structural proteins including E (envelope protein), GP2, GP3, and GP4 (encoded by ORF 2, 3, and 4 respectively) may also contribute to the formation of infectious virus particles. A recent study has demonstrated a partial protection of PRRSV VLPs vaccine composed of five structural proteins including GP3, GP4, GP5, E, and M against homologous challenge when delivered together with PLGA nanoparticles [3]. In this study, we generated VLPs by expressing four PRRSV structural proteins including M, N, GP5, and E and assessed their immunogenicity and protective efficacy in pigs.…”

“…Several previous studies have reported the immunogenicity of PRRSV VLPs or chimera VLPs containing GP5 or GP5 and M proteins or the conserved protective epitopes of viral structural proteins in mice [19, 20, 26, 27]. Only one recent study described the partial protection against PRRSV in pigs immunized with PRRSV VLPs containing GP2, GP3, GP4, GP5 and M proteins [3]. More research is needed to fully explore the potential utility of VLPs in PRRSV vaccine development.…”

A highly pathogenic porcine reproductive and respiratory syndrome virus candidate vaccine based on Japanese encephalitis virus replicon system

“…The GP5 protein and M protein have been shown to induce antibodies and high production of IFN- β (Binjawadagi et al, 2016). Here, we describe the construction of JEV replicons and use JEV replicon vectors expressing the PRRSV GP5 and M proteins as a bivalent seedlings vaccine.…”