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Open AccessArticle

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

1
VIM, INRA, Université Paris-Saclay, Domaine de Vilvert, 78350 Jouy-en-Josas, France
2
Vaccibody AS, Gaustadalleen 21, 0349 Oslo, Norway
3
Vaccine Formulation Laboratory, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland
4
Plate-Forme d’Infectiologie Expérimentale-PFIE-UE1277, INRA, 37380 Nouzilly, France
5
Immunology of viral infections and autoimmune diseases, IDMIT Department, IBFJ, INSERM U1184-CEA-Université Paris Sud 11, 92260 Fontenay-Aux-Roses et 94270 Le Kremlin-Bicêtre, France
6
Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium
*
Author to whom correspondence should be addressed.
Current address: BIOEPAR, Oniris, INRA, 44307 Nantes, France.
Viruses 2019, 11(6), 551; https://doi.org/10.3390/v11060551
Received: 20 May 2019 / Revised: 3 June 2019 / Accepted: 11 June 2019 / Published: 14 June 2019
(This article belongs to the Special Issue Porcine Viruses 2019)
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. View Full-Text
Keywords: PRRSV; DNA vaccine; modified-live vaccine; antigen-presenting cell targeting; pigs PRRSV; DNA vaccine; modified-live vaccine; antigen-presenting cell targeting; pigs
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Bernelin-Cottet, C.; Urien, C.; Stubsrud, E.; Jakob, V.; Bouguyon, E.; Bordet, E.; Barc, C.; Boulesteix, O.; Contreras, V.; Barnier-Quer, C.; Collin, N.; Trus, I.; Nauwynck, H.; Bertho, N.; Schwartz-Cornil, I. 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. Viruses 2019, 11, 551.

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