Immune responses in mice vaccinated with virus-like particles composed of the GP5 and M proteins of porcine reproductive and respiratory syndrome virus

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) induces reproductive failure in sows and respiratory problems in pigs of all ages. Live attenuated and inactivated vaccines are used on swine farms to control PRRSV. However, their protective efficacy against field strains of PRRSV remains questionable. New vaccines have been developed to improve the efficacy of these traditional vaccines. In this study, virus-like particles (VLPs) composed of the GP5 and M proteins of PRRSV were developed, and the capacity of the VLPs to elicit antigen-specific immunity was evaluated. Serum antibody titers and production of cytokines were measured in BALB/C mice immunized intramuscularly three times with different doses (0.5, 1.0, 2.0, and 4.0 μ) of the VLP vaccine. A commercial vaccine consisting of inactivated PRRSV and phosphate-buffered saline (PBS) were used as positive and negative controls, respectively. IgG titers to GP5 were significantly higher in all groups of mice vaccinated with the VLPs than in control mice. Neutralizing antibodies were only detected in mice vaccinated with 2.0 and 4.0 μ of the VLPs. Cytokine levels were determined in cell culture supernatants after in vitro stimulation of splenocytes with the VLPs for 3 days. Mice immunized with 4.0 μ of the VLPs produced a significantly higher amount of interferon-gamma (IFN-γ) than mice immunized with the commercial inactivated PRRSV vaccine and PBS. In contrast, immunization with the commercial vaccine induced higher production of IL-4 and IL-10 in mice than mice vaccinated with VLPs. These data together demonstrate the capacity of VLPs to induce both neutralizing antibodies and IFN-γ in immunized mice. The VLP vaccine developed in this study could serve as a platform for the generation of improved VLP vaccines to control PRRSV.

Porcine Reproductive and Respiratory Syndrome Virus Utilizes Nanotubes for Intercellular Spread

“…In contrast, significant amounts of GP5 proteins were detected associated with intercellular nanotubes. It was reported that a GP5/M protein heterodimer of arterivirus plays an important role in viral envelope formation (37)(38)(39). GP5 and M have been proposed to be the driving force for virus budding, which may be involved in the formation of the highly curved edges of the membrane (reviewed in reference 40).…”

Recombinant Encephalomyocarditis Viruses Elicit Neutralizing Antibodies against PRRSV and CSFV in Mice

“…Although GP5 fusion protein had a 23-amino-acid linear epitope deletion at the C-terminus, CvBJC3m/I-ΔGP5 still maintained the neutralization epitopes located in the middle of GP5 ectodomain [29] and is able to induce mild neutralizing antibodies in mice. This result is not surprising since it has been reported that virus-like particles composed of PRRSV GP5 and M protein were capable of eliciting neutralizing antibodies during mice immunization [30]. However, whether the phenotype observed in our mice model would be able to translate into porcine vaccine development is still questionable as PRRSV GP5-based vaccines only induce unsatisfactory neutralization antibodies and confer limited protection upon challenge [31–33].…”

Virus-Like Particle Vaccine Confers Protection against a Lethal Newcastle Disease Virus Challenge in Chickens and Allows a Strategy of Differentiating Infected from Vaccinated Animals

“…The key advantage of this recombinant protein manufacturing platform is that it can perform most of the posttranslational modifications (e.g., glycosylation, disulfide bond formation, and phosphorylation) and thus can produce biologically active proteins while offering the potential for low manufacturing costs. Moreover, insect cell expression systems have been widely used for the development of various VLP vaccines against both human and animal viruses (15,16,(18)(19)(20).…”