Cholera toxin-B (ctxB) antigen expressing Salmonella Typhimurium polyvalent vaccine exerts protective immune response against Vibrio cholerae infection |
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| Affiliation: | 1. School of Biotechnology, KIIT University, Bhubaneswar 751024, Odisha, India;2. Institute of Microbiology, ETH Zurich, Zurich, Switzerland;1. Unidad de BiotecnologíaMédica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco A.C., Guadalajara, Jalisco 44270, Mexico;2. Departamento de Microbiología e Inmunología, Facultad de MedicinaVeterinaria y Zootecnia, Universidad NacionalAutónoma de México, México, D.F. 04510, Mexico;3. Centro Nacional de Investigación Disciplinaria en Microbiología, Instituto Nacional de Investigaciones Forestales, Agrícolas y Pecuarias, México, D.F. 05110, Mexico;4. Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco 44340, Mexico;5. Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco 44340, Mexico;1. Professor, Department of Microbiology, Armed Forces Medical College, Pune 411040, India;2. Director, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata 700010, India;3. Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106;4. Translational Hematology and Oncology Research, Cleveland Clinic Foundation, Cleveland, Ohio 44106;1. Immunology Department, Finlay Institute, Havana, Cuba;2. Animal Models Group, Direction of Research and Development, Finlay Institute, Havana, Cuba;1. Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650031, PR China;2. Technology Center, China Tobacco Yunnan Industry Company (Ltd.), Kunming 650000, PR China |
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| 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. |
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| Keywords: | Live attenuated vaccine: LAV Z234-pMS101 vaccine Polyvalent vaccine ctxB Cholera Salmonellosis Immunocompromised host |
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