A DNA-Modified Live Vaccine Prime-Boost Strategy Broadens the T-Cell Response and Enhances the Antibody Response against the Porcine Reproductive and Respiratory Syndrome Virus.

Cindy Bernelin-Cottet,Olivier Boulesteix,Isabelle Schwartz-Cornil,Ivan Trus,Christophe Barnier-Quer,Céline Barc,Vanessa Contreras,Elise Bordet,Nicolas Collin,Edwige Bouguyon,Virginie Jakob,Céline Urien,Nicolas Bertho,Hans Nauwynck,Elisabeth Stubsrud

doi:10.3390/v11060551

Abstract

The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) induces reproductive disorders in sows and respiratory illnesses in growing pigs and is considered as one of the main pathogenic agents responsible for economic losses in the porcine industry worldwide. Modified live PRRSV vaccines (MLVs) are very effective vaccine types against homologous strains but they present only partial protection against heterologous viral variants. With the goal to induce broad and cross-protective immunity, we generated DNA vaccines encoding B and T antigens derived from a European subtype 1 strain that include T-cell epitope sequences known to be conserved across strains. These antigens were expressed either in a native form or in the form of vaccibodies targeted to the endocytic receptor XCR1 and CD11c expressed by different types of antigen-presenting cells (APCs). When delivered in skin with cationic nanoparticles and surface electroporation, multiple DNA vaccinations as a stand-alone regimen induced substantial antibody and T-cell responses, which were not promoted by targeting antigens to APCs. Interestingly, a DNA-MLV prime–boost strategy strongly enhanced the antibody response and broadened the T-cell responses over the one induced by MLV or DNA-only. The anti-nucleoprotein antibody response induced by the DNA-MLV prime–boost was clearly promoted by targeting the antigen to CD11c and XCR1, indicating a benefit of APC-targeting on the B-cell response. In conclusion, a DNA-MLV prime–boost strategy, by enhancing the potency and breadth of MLV vaccines, stands as a promising vaccine strategy to improve the control of PRRSV in infected herds.

Highlights

The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), a positive-strand RNA virus of the Arteriviridae family, induces respiratory illness in neonatal and in recently-weaned piglets as well as late abortions/early farrowing in sows and is responsible for major economic losses in the swine industry worldwide [1]
We selected sequences from six PRRSV AG derived from the FL13 isolate (PRRSV-1, subtype 1) to to be expressed by DNA vectors in a native form or in vaccibody platforms in order be expressed by DNA vectors in a native form or in vaccibody platforms in order to target these AG to antigen-presenting cells (APCs) with the goal to induce high and broad T-cell responses (Figure 1A,B)
Our work shows that the DNA-modified live vaccines (MLVs) prime–boost strategy broadens the T-cell response and increases the antibody response over DNA-only and MLV-only regimens, and it can be considered for the rational design of broadly efficacious vaccines against PRRSV

Summary

Introduction

The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), a positive-strand RNA virus of the Arteriviridae family, induces respiratory illness in neonatal and in recently-weaned piglets as well as late abortions/early farrowing in sows and is responsible for major economic losses in the swine industry worldwide [1]. This virus, which primarily infects only certain types of macrophages including pulmonary alveolar macrophages, exists in two distinct species, PRRSV-1 and PRRSV-2, which are the dominating species in Europe and North America, respectively [1,2]. MLVs revealed safety concerns with reversion to pathogenicity and only demonstrated partial protection against heterologous strains

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