title: Construction, characterization and evaluation of the protective efficacy of the Streptococcus suis double mutant strain ΔSsPep/ΔSsPspC as a live vaccine candidate in mice.
abstract: Streptococcus suis serotype 2 (S. suis 2) causes sepsis and meningitis in piglets and humans, and results in one of the most serious bacterial diseases affecting the production of commercial pigs around the world. Due to the failure of the current inactivated vaccine to protect against the disease, development of a new attenuated live vaccine against S. suis 2 by deleting essential virulence factors is urgently needed. We have previously reported the construction and characterization of an SsPep single gene deletion mutant strain ΔSsPep based on S. suis 2. Our previous results have shown that SsPep plays a critical role in the pathogenesis of S. suis 2. In this study, a precisely defined double-deletion mutant ΔSsPep/ΔSsPspC of S. suis 2 without antibiotic-resistance markers was constructed based on ΔSsPep, and the levels of virulence of the wild-type (WT) and ΔSsPep/ΔSsPspC were compared in a mouse experimental infection model. We demonstrated that the double mutant ΔSsPep/ΔSsPspC was less virulent than the WT, and could induce a noticeable antibody response. Analysis of IgG subclasses (IgG1 and IgG2a) indicated that both Th1 and Th2 responses were induced by ΔSsPep/ΔSsPspC, although the IgG2a (Th1) response predominated over the IgG1 (Th2) response. Moreover, ΔSsPep/ΔSsPspC could confer 90% protective efficacy against challenge with a lethal dose of fully virulent S. suis 2. Taken together, these data demonstrate that ΔSsPep/ΔSsPspC can be used as an effective live vaccine and provide a novel strategy against infection of S. suis 2.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China; College of Animal Science & Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China; College of Animal Science & Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Wujin
authors.initials: W
authors.lastname: You
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China; College of Animal Science & Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: College of Animal Science & Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China; College of Animal Science & Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Tan
authors.affiliation: College of Life Science, Central China Normal University, Wuhan, Hubei 430079, China.
authors.forename: Jinlin
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China; College of Animal Science & Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China. Electronic address: chenhch@mail.hzau.edu.cn.
authors.forename: Huanchun
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China; College of Animal Science & Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China. Electronic address: beiwc@mail.hzau.edu.cn.
authors.forename: Weicheng
authors.initials: W
authors.lastname: Bei
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005798:Genes, Bacterial; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009154:Mutation; D013290:Streptococcal Infections / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D017011:Streptococcus suis / Q000235:genetics* / Q000276:immunology*; D062690:Vaccines, Live, Unattenuated; D014774:Virulence / Q000235:genetics
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines; D007074:Immunoglobulin G; D022541:Streptococcal Vaccines; D062690:Vaccines, Live, Unattenuated
keywords: Immune response; Live vaccine; Protective efficacy; Streptococcus suis 2; ΔSsPep/ΔSsPspC