title: Live attenuated Salmonella enterica serovar Choleraesuis vaccine vector displaying regulated delayed attenuation and regulated delayed antigen synthesis to confer protection against Streptococcus suis in mice.
abstract: Salmonella enterica serotype Choleraesuis (S. Choleraesuis) and Streptococcus suis (S. suis) are important swine pathogens. Development of a safe and effective attenuated S. Choleraesuis vaccine vector would open a new window to prevent and control pig diseases. To achieve this goal, the mannose and arabinose regulated delayed attenuated systems (RDAS), Δpmi and ΔPcrp::TT araC PBADcrp, were introduced into the wild type S. Choleraesuis strain C78-3. We also introduced ΔrelA::araC PBADlacI TT to achieve regulated delayed antigen synthesis and ΔasdA to constitute a balanced-lethal plasmid system. The safety and immunogenicity of the resulted RDAS S. Choleraesuis strain rSC0011 carrying 6-phosphogluconate dehydrogenase (6-PGD) of S. suis serotype 2 (SS2) were evaluated in vitro and in vivo. Compared with the wild type parent strain C78-3 and vaccine strain C500, a live attenuated S. Choleraesuis vaccine licensed for piglet in China, the results showed that the survival curves of the vaccine strain rSC0011 were similar to those of strains C78-3 and C500 at the early stage of infection, but lower than those of C78-3 and higher than those of C500 at the later stage in both porcine alveolar macrophages and peripheral porcine monocytes. The LD50 of the RDAS strains rSC0011 by oral route in mice was close to that of C500 and 10,000-fold higher than that of C78-3. Similar results were achieved by intraperitoneal (i.p.) route, suggesting that the RDAS strains rSC0011 achieved similar attenuation as C500. However, the RDAS strain rSC0011 was superior to C500 in colonization of Peyer's patches. Adult mice orally immunized with strain rSC0011 carrying a plasmid expression 6-phosphogluconate dehydrogenase (6-PGD) gene from SS2 developed strong immune responses against 6-PGD and Salmonella antigens, and conferred high protection against i.p. challenge with SS2.
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-Innovation Center of Jiangsu for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China.
authors.forename: Zhenying
authors.initials: Z
authors.lastname: Ji
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-Innovation Center of Jiangsu for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shang
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-Innovation Center of Jiangsu for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Center for Infectious Diseases and Vaccinology, The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ 85287-5401, USA; Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611-0880, USA.
authors.forename: Shifeng
authors.initials: S
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-Innovation Center of Jiangsu for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China. Electronic address: hyshi@yzu.edu.cn.
authors.forename: Huoying
authors.initials: H
authors.lastname: Shi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000942:Antigens, Bacterial / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D004337:Drug Carriers; D015964:Gene Expression Regulation, Bacterial; D007928:Lethal Dose 50; D051379:Mice; D019779:Salmonella enterica / Q000235:genetics* / Q000254:growth & development; D013290:Streptococcal Infections / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary*; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D017011:Streptococcus suis / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis; D016896:Treatment Outcome; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D004337:Drug Carriers; D022541:Streptococcal Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic
keywords: 6-PGD; Regulated delayed antigen synthesis; Regulated delayed attenuation system; Salmonella Choleraesuis; Streptococcus suis