title: Cholera toxin-B (ctxB) antigen expressing Salmonella Typhimurium polyvalent vaccine exerts protective immune response against Vibrio cholerae infection.
abstract: Live attenuated vaccines are cost effective approach for preventing a broad range of infectious diseases, and thus are of great interest. However, immune-defects can predispose the patient to infections by the vaccine candidate itself. So far, few live vaccine candidates have been designed specifically for immune compromised individuals. Recently, we reported a new Salmonella Typhimurium Z234-vaccine strain (Periaswamy et al., PLoS ONE 2012;7:e45433), which was specifically attenuated in the NADPH-oxidase deficient host. In the present study, the Z234-vaccine strain was further engineered to express heterologous antigen (Vibrio cholerae toxin antigen subunit-B, i.e. CtxB) with the intention of creating a vector for simultaneous protection against Cholera and Salmonellosis. The primary aim of this study was to ensure the expression of CtxB antigen by the recombinant vaccine strain Z234-pMS101. The antigen CtxB was expressed through Z234 as a fusion protein with N-terminal signal sequence of Salmonella outer protein (SopE), an effector protein from Salmonella under the control of SopE promoter. The CtxB-expressing plasmid construct pMS101 (pM968-pSopE-ctxB) was found to be stable both in vitro and in vivo. In an oral mouse infection model, the vaccine strain Z234-pMS101 efficiently colonized the host gut. The extent of protection was confirmed after challenging the immunized hosts with live V. cholerae. Vaccinated mice showed reduced gut colonization by V. cholerae. Further assessment of immunological parameters supported the possibility of conferring effective immune response by Z234-pMS101 vaccine strain. Overall, the Z234-pMS101 vaccine strain showed potential as a promising polyvalent vaccine candidate to protect against S. Typhimurium and V. cholerae infection simultaneously.
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar 751024, Odisha, India.
authors.forename: Vikalp
authors.initials: V
authors.lastname: Vishwakarma
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar 751024, Odisha, India.
authors.forename: Sushree Sangita
authors.initials: SS
authors.lastname: Sahoo
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar 751024, Odisha, India.
authors.forename: Susmita
authors.initials: S
authors.lastname: Das
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar 751024, Odisha, India.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Ray
authors.affiliation: Institute of Microbiology, ETH Zurich, Zurich, Switzerland.
authors.forename: Wolf-Dietrich
authors.initials: WD
authors.lastname: Hardt
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar 751024, Odisha, India. Electronic address: msbiotek@yahoo.com.
authors.forename: Mrutyunjay
authors.initials: M
authors.lastname: Suar
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D015478:Antigens, Heterophile / Q000235:genetics / Q000276:immunology; D002432:Cecum / Q000382:microbiology / Q000473:pathology; D002771:Cholera / Q000517:prevention & control*; D002772:Cholera Toxin / Q000235:genetics / Q000276:immunology*; D022121:Cholera Vaccines / Q000276:immunology*; D004195:Disease Models, Animal; D005243:Feces / Q000382:microbiology; D005822:Genetic Vectors; D007111:Immunity, Cellular; D016867:Immunocompromised Host; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D012481:Salmonella Infections, Animal / Q000517:prevention & control*; D022562:Salmonella Vaccines / Q000276:immunology*; D012486:Salmonella typhimurium / Q000254:growth & development / Q000276:immunology*; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014734:Vibrio cholerae / Q000254:growth & development
chemical_list: D000907:Antibodies, Bacterial; D015478:Antigens, Heterophile; D022121:Cholera Vaccines; D011994:Recombinant Proteins; D022562:Salmonella Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D002772:Cholera Toxin
keywords: Cholera; Immunocompromised host; Live attenuated vaccine: LAV; Polyvalent vaccine; Salmonellosis; Z234-pMS101 vaccine; ctxB