1d9293d7a6201603a299ad9508cebb82 pmc_9502879.pdf 66a1fb647b3d7908d79549176dedce20ffab47a4 pmc_9502879.pdf 0363071ed5bb775df9d379526c3eff34b6a8091bb199b1181a3eff4625175850 pmc_9502879.pdf Title: The FlagT4G Vaccine Confers a Strong and Regulated Immunity and Early Virological Protection against Classical Swine Fever Subject: Control of classical swine fever virus (CSFV) in endemic countries relies on vaccination, mostly using vaccines that do not allow for differentiation of vaccinated from infected animals (DIVA). FlagT4G vaccine is a novel candidate that confers robust immunity and shows DIVA capabilities. The present study assessed the immune response elicited by FlagT4G and its capacity to protect pigs for a short time after vaccination. Five days after a single dose of FlagT4G vaccine, animals were challenged with a highly virulent CSFV strain. A strong, but regulated, interferon- response was found after vaccination. Vaccinated animals showed clinical and virological protection against the challenge, in the absence of antibody response at 5 days post-vaccination. Upon challenge, a rapid rise in the titers of CSFV neutralizing antibodies and an increase in the IFN- producing cells were noticed in all vaccinated-challenged pigs. Meanwhile, unvaccinated pigs showed severe clinical signs and high viral replication, being euthanized before the end of the trial. These animals were unable to generate neutralizing antibodies and IFN- responses after the CSFV challenge. The results from the present study assert the fast and efficient protection by FlagT4G, a highly promising tool for CSFV control worldwide. Keywords: vaccine efficacy; CSFV; innate immunity; FlagT4G; marker vaccine; virological protection; antibody response Author: José Alejandro Bohórquez, Miaomiao Wang, Ivan Díaz, Mònica Alberch, Marta Pérez-Simó, Rosa Rosell, Douglas P. Gladue, Manuel V. Borca and Llilianne Ganges Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Sep 2 15:53:42 2022 CEST ModDate: Fri Sep 2 17:26:30 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2696130 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- RAFMMA+VnURWPalladioL Type 1 Custom yes yes no 10 0 LEVXPH+EURM10 Type 1 Builtin yes yes no 15 0 OTXYXU+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 KMBMTF+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 KPICHW+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 RNXXBO+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 HOWKDX+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 50 0 PDYDVH+CMSY10 Type 1 Builtin yes yes no 75 0 GEWEQC+PazoMath-Italic Type 1 Builtin yes yes no 82 0 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edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4923ab24 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Children: Item: Title: Cells and Viruses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Experimental Design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Antibody Detection by ELISA and Virus Neutralization Assay Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Evaluation of the Cytokine Response by ELISA and Luminex Assays Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Detection of CSFV RNA Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: PBMC Collection Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Assessment of Cellular Immune Response by IFN- ELISPOT Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Phenotypical Profile Evaluation by Flow Cytometry Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Children: Item: Title: FlagT4G Affords Early Clinical Protection against CSFV Challenge in Pigs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: FlagT4G Induced Fast Protection after Five Days of Vaccination in the Absence of Antibody Response Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Cytokine Response after FlagT4G Vaccination and CSFV Challenge Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: The FlagT4G Vaccine Induces Rapid Protection against Systemic Viral Replication Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: FlagT4G Vaccination Improves Cellular Immune Response in Swine Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Info: Title: The FlagT4G Vaccine Confers a Strong and Regulated Immunity and Early Virological Protection against Classical Swine Fever Author: José Alejandro Bohórquez, Miaomiao Wang, Ivan Díaz, Mònica Alberch, Marta Pérez-Simó, Rosa Rosell, Douglas P. Gladue, Manuel V. Borca and Llilianne Ganges Subject: Control of classical swine fever virus (CSFV) in endemic countries relies on vaccination, mostly using vaccines that do not allow for differentiation of vaccinated from infected animals (DIVA). FlagT4G vaccine is a novel candidate that confers robust immunity and shows DIVA capabilities. The present study assessed the immune response elicited by FlagT4G and its capacity to protect pigs for a short time after vaccination. Five days after a single dose of FlagT4G vaccine, animals were challenged with a highly virulent CSFV strain. A strong, but regulated, interferon- response was found after vaccination. Vaccinated animals showed clinical and virological protection against the challenge, in the absence of antibody response at 5 days post-vaccination. Upon challenge, a rapid rise in the titers of CSFV neutralizing antibodies and an increase in the IFN- producing cells were noticed in all vaccinated-challenged pigs. Meanwhile, unvaccinated pigs showed severe clinical signs and high viral replication, being euthanized before the end of the trial. These animals were unable to generate neutralizing antibodies and IFN- responses after the CSFV challenge. The results from the present study assert the fast and efficient protection by FlagT4G, a highly promising tool for CSFV control worldwide. 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