A Triple Gene-Deleted Pseudorabies Virus-Vectored Subunit PCV2b and CSFV Vaccine Protects Pigs against PCV2b Challenge and Induces Serum Neutralizing Antibody Response against CSFV.

Selvaraj Pavulraj,Mariano Carossino,Rhett W Stout,Katrin Pannhorst,Denise Meyer,Paul Becher,Shafiqul I Chowdhury,Daniel B Paulsen

doi:10.3390/vaccines10020305

Selvaraj Pavulraj, Mariano Carossino + Show 6 more

Open Access

https://doi.org/10.3390/vaccines10020305

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Abstract

Porcine circovirus type 2 (PCV2) is endemic worldwide. PCV2 causes immunosuppressive infection. Co-infection of pigs with other swine viruses, such as pseudorabies virus (PRV) and classical swine fever virus (CSFV), have fatal outcomes, causing the swine industry significant economic losses in many if not all pig-producing countries. Currently available inactivated/modified-live/vectored vaccines against PCV2/CSFV/PRV have safety and efficacy limitations. To address these shortcomings, we have constructed a triple gene (thymidine kinase, glycoprotein E [gE], and gG)-deleted (PRVtmv) vaccine vector expressing chimeric PCV2b-capsid, CSFV-E2, and chimeric Erns-fused with bovine granulocytic monocyte-colony stimulating factor (Erns-GM-CSF), designated as PRVtmv+, a trivalent vaccine. Here we compared this vaccine’s immunogenicity and protective efficacy in pigs against wild-type PCV2b challenge with that of the inactivated Zoetis Fostera Gold PCV commercial vaccine. The live PRVtmv+ prototype trivalent subunit vaccine is safe and highly attenuated in pigs. Based on PCV2b-specific neutralizing antibody titers, viremia, viral load in lymphoid tissues, fecal-virus shedding, and leukocyte/lymphocyte count, the PRVtmv+ yielded better protection for vaccinated pigs than the commercial vaccine after the PCV2b challenge. Additionally, the PRVtmv+ vaccinated pigs generated low to moderate levels of CSFV-specific neutralizing antibodies.

Highlights

This study study constructed constructed PRVtmv, PRVtmv, aa triple triple mutant mutant virus virus lacking lacking the the entire entire glycoprotein E (gE)
GE gene, gene, aa serological marker distinguishing the vaccinated from the wt virus-infected pigs (DIVA)
FurtherErns-GM-Classical swine fever (CSF) genes were inserted in the gE- and glycoprotein G (gG)- deletion loci, respectively

Summary

Introduction

Porcine circovirus type 2 (PCV2) is endemic in most, if not all, intensive pig farms worldwide, including the United States, as evidenced by a remarkably high seroprevalence [1]. The virus was first isolated from pigs with the post-weaning multisystemic wasting syndrome (PMWS) in the 1990s [2]. PCV2 infection can lead to immunosuppression and cytokine imbalance [3]. PCV2 alone causes only sub-clinical disease, because of its immunosuppressive nature, PCV2 co-infection with Mycoplasma spp., parvovirus, or porcine reproductive and respiratory syndrome virus (PRRSV) may cause the clinical disease designated as PMWS [4]. The preexisting PCV2 infection decreases the efficacy of vaccines. Coinfection of PCV2 with swine influenza virus (SIV), classical swine fever virus (CSFV), and pseudorabies virus (PRV) increases the pathogenicity of these infections [5]. PCV2associated diseases pose a significant problem for the pig industry worldwide [6] and cause substantial economic losses in many pig-producing countries, including the USA

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