PMID- 31242645 OWN - NLM STAT- MEDLINE DCOM- 20200724 LR - 20231012 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 11 IP - 6 DP - 2019 Jun 25 TI - A DNA Prime Immuno-Potentiates a Modified Live Vaccine against the Porcine Reproductive and Respiratory Syndrome Virus but Does Not Improve Heterologous Protection. LID - 10.3390/v11060576 [doi] LID - 576 AB - The porcine reproductive and respiratory syndrome virus (PRRSV), an RNA virus inducing abortion in sows and respiratory disease in young pigs, is a leading infectious cause of economic losses in the swine industry. Modified live vaccines (MLVs) help in controlling the disease, but their efficacy is often compromised by the high genetic diversity of circulating viruses, leading to vaccine escape variants in the field. In this study, we hypothesized that a DNA prime with naked plasmids encoding PRRSV antigens containing conserved T-cell epitopes may improve the protection of MLV against a heterologous challenge. Plasmids were delivered with surface electroporation or needle-free jet injection and European strain-derived PRRSV antigens were targeted or not to the dendritic cell receptor XCR1. Compared to MLV-alone, the DNA-MLV prime- boost regimen slightly improved the IFNgamma T-cell response, and substantially increased the antibody response against envelope motives and the nucleoprotein N. The XCR1-targeting of N significantly improved the anti-N specific antibody response. Despite this immuno-potentiation, the DNA-MLV regimen did not further decrease the serum viral load or the nasal viral shedding of the challenge strain over MLV-alone. Finally, the heterologous protection, achieved in absence of detectable effective neutralizing antibodies, was not correlated to the measured antibody or to the IFNgamma T-cell response. Therefore, immune correlates of protection remain to be identified and represent an important gap of knowledge in PRRSV vaccinology. This study importantly shows that a naked DNA prime immuno-potentiates an MLV, more on the B than on the IFNgamma T-cell response side, and has to be further improved to reach cross-protection. FAU - Bernelin-Cottet, Cindy AU - Bernelin-Cottet C AD - VIM, INRA, Universite Paris-Saclay, Domaine de Vilvert, 78350 Jouy-en-Josas, France. bernelin.cottet.cindy@hotmail.fr. FAU - Urien, Celine AU - Urien C AD - VIM, INRA, Universite Paris-Saclay, Domaine de Vilvert, 78350 Jouy-en-Josas, France. celine.urien@inra.fr. FAU - Fretaud, Maxence AU - Fretaud M AD - VIM, INRA, Universite Paris-Saclay, Domaine de Vilvert, 78350 Jouy-en-Josas, France. maxence.fretaud@inra.fr. FAU - Langevin, Christelle AU - Langevin C AUID- ORCID: 0000-0002-6013-4460 AD - VIM, INRA, Universite Paris-Saclay, Domaine de Vilvert, 78350 Jouy-en-Josas, France. christelle.langevin@inra.fr. AD - VIM, EMERG'IN-Plateforme d'Infectiologie Experimentale IERP, INRA, Domaine de Vilvert, 78352 Jouy-en-Josas, France. christelle.langevin@inra.fr. FAU - Trus, Ivan AU - Trus I AUID- ORCID: 0000-0003-2849-5140 AD - Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium. ivan.trus@gmail.com. FAU - Jouneau, Luc AU - Jouneau L AUID- ORCID: 0000-0002-5094-7302 AD - VIM, INRA, Universite Paris-Saclay, Domaine de Vilvert, 78350 Jouy-en-Josas, France. luc.jouneau@inra.fr. FAU - Blanc, Fany AU - Blanc F AUID- ORCID: 0000-0003-2366-9826 AD - GABI, INRA-AgroParisTech, Universite Paris-Saclay, Domaine de Vilvert, 78350 Jouy-en-Josas, France. Fany.blanc@inra.fr. FAU - Leplat, Jean-Jacques AU - Leplat JJ AD - GABI, INRA-AgroParisTech, Universite Paris-Saclay, Domaine de Vilvert, 78350 Jouy-en-Josas, France. jeanjacques.leplat@inra.fr. FAU - Barc, Celine AU - Barc C AD - Plate-Forme d'Infectiologie Experimentale-PFIE-UE1277, Centre Val de Loire, INRA, 37380 Nouzilly, France. celine.barc@inra.fr. FAU - Boulesteix, Olivier AU - Boulesteix O AD - Plate-Forme d'Infectiologie Experimentale-PFIE-UE1277, Centre Val de Loire, INRA, 37380 Nouzilly, France. olivier.boulesteix@inra.fr. FAU - Riou, Mickael AU - Riou M AD - Plate-Forme d'Infectiologie Experimentale-PFIE-UE1277, Centre Val de Loire, INRA, 37380 Nouzilly, France. mickael.riou@inra.fr. FAU - Dysart, Marilyn AU - Dysart M AD - Pharmajet, 400 Corporate Circle Suite N, Golden, CO 80401, USA. marilyn.dysart@pharmajet.com. FAU - Mahe, Sophie AU - Mahe S AD - Unite Virologie et Immunologie Porcines, Laboratoire de Ploufragan-Plouzane-Niort, Anses, BP 53, 22440 Ploufragan, France. sophie.mahe@anses.fr. FAU - Studsrub, Elisabeth AU - Studsrub E AD - Vaccibody AS, Gaustadalleen 21, 0349 Oslo, Norway. estubsrud@vaccibody.com. FAU - Nauwynck, Hans AU - Nauwynck H AUID- ORCID: 0000-0001-5470-0713 AD - Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium. hans.nauwynck@ugent.be. FAU - Bertho, Nicolas AU - Bertho N AD - VIM, INRA, Universite Paris-Saclay, Domaine de Vilvert, 78350 Jouy-en-Josas, France. nicolas.bertho@inra.fr. FAU - Bourry, Olivier AU - Bourry O AUID- ORCID: 0000-0003-0220-0922 AD - Unite Virologie et Immunologie Porcines, Laboratoire de Ploufragan-Plouzane-Niort, Anses, BP 53, 22440 Ploufragan, France. olivier.bourry@anses.fr. FAU - Schwartz-Cornil, Isabelle AU - Schwartz-Cornil I AUID- ORCID: 0000-0002-3485-1765 AD - VIM, INRA, Universite Paris-Saclay, Domaine de Vilvert, 78350 Jouy-en-Josas, France. isabelle.schwartz@inra.fr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190625 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 RN - 0 (Antibodies, Neutralizing) RN - 0 (Antibodies, Viral) RN - 0 (Immunologic Factors) RN - 0 (Vaccines, Attenuated) RN - 0 (Vaccines, DNA) RN - 0 (Viral Vaccines) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Antibodies, Neutralizing/blood MH - Antibodies, Viral/blood MH - *Immunity, Heterologous MH - *Immunization Schedule MH - Immunologic Factors/metabolism MH - Interferon-gamma/metabolism MH - Nasal Mucosa/virology MH - Porcine Reproductive and Respiratory Syndrome/*prevention & control MH - Porcine respiratory and reproductive syndrome virus/genetics/*immunology MH - Swine MH - T-Lymphocytes/immunology MH - Treatment Outcome MH - Vaccines, Attenuated/administration & dosage/immunology MH - Vaccines, DNA/administration & dosage/*immunology MH - Viral Load MH - Viral Vaccines/administration & dosage/*immunology MH - Virus Shedding PMC - PMC6631340 OTO - NOTNLM OT - DNA vaccine OT - PRRSV OT - antigen-presenting cell targeting OT - modified-live vaccine OT - pigs COIS- PharmaJet declares that they have no significant competing financial, professional, or personal interests that might have influenced the performance or presentation of the work described in this manuscript. Elisabeth Stubsrud is employed by Vaccibody AS and has financial interests in the company. The other authors declare no conflict of interest. EDAT- 2019/06/28 06:00 MHDA- 2020/07/25 06:00 PMCR- 2019/06/01 CRDT- 2019/06/28 06:00 PHST- 2019/05/20 00:00 [received] PHST- 2019/06/18 00:00 [revised] PHST- 2019/06/21 00:00 [accepted] PHST- 2019/06/28 06:00 [entrez] PHST- 2019/06/28 06:00 [pubmed] PHST- 2020/07/25 06:00 [medline] PHST- 2019/06/01 00:00 [pmc-release] AID - v11060576 [pii] AID - viruses-11-00576 [pii] AID - 10.3390/v11060576 [doi] PST - epublish SO - Viruses. 2019 Jun 25;11(6):576. doi: 10.3390/v11060576.