title: A colanic acid operon deletion mutation enhances induction of early antibody responses by live attenuated Salmonella vaccine strains.
abstract: Colanic acid (CA) is a common exopolysaccharide produced by many genera in the Enterobacteriaceae. It is critical for biofilm formation on HEp-2 cells and on chicken intestinal tissue by Salmonella. In this study, we generated different CA synthesis gene mutants and evaluated the immune responses induced by these mutants. One of these mutations, Δ(wza-wcaM)8, which deleted the whole operon for CA synthesis, was introduced into two Salmonella vaccine strains attenuated by auxotrophic traits or by the regulated delayed attenuation strategy (RDAS). The mice immunized with the auxotrophic Salmonella vaccine strain with the deletion mutation Δ(wza-wcaM)8 developed higher vaginal IgA titers against the heterologous protective antigen and higher levels of antigen-specific IgA secretion cells in lungs. In Salmonella vaccine strains with RDAS, the strain with the Δ(wza-wcaM)8 mutation resulted in higher levels of protective antigen production during in vitro growth. Mice immunized with this strain developed higher serum IgG and mucosal IgA antibody responses at 2 weeks. This strain also resulted in better gamma interferon (IFN-γ) responses than the strain without this deletion at doses of 10(8) and 10(9) CFU. Thus, the mutation Δ(wza-wcaM)8 will be included in various recombinant attenuated Salmonella vaccine (RASV) strains with RDAS derived from Salmonella enterica serovar Paratyphi A and Salmonella enterica serovar Typhi to induce protective immunity against bacterial pathogens.
authors.affiliation: Center for Infectious Diseases and Vaccinology, The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona, USA.
authors.forename: Shifeng
authors.initials: S
authors.lastname: Wang
authors.forename: Huoying
authors.initials: H
authors.lastname: Shi
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Li
authors.forename: Zhaoxing
authors.initials: Z
authors.lastname: Shi
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Chang-Ho
authors.initials: CH
authors.lastname: Baek
authors.forename: Tabor
authors.initials: T
authors.lastname: Mothershead
authors.forename: Roy
authors.initials: R
authors.lastname: Curtiss
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000235:genetics / Q000276:immunology; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology*; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D005260:Female; D007070:Immunoglobulin A / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009876:Operon / Q000235:genetics* / Q000276:immunology; D011134:Polysaccharides / Q000235:genetics* / Q000276:immunology; D012475:Salmonella / Q000235:genetics / Q000276:immunology*; D022562:Salmonella Vaccines / Q000235:genetics / Q000276:immunology*; D017384:Sequence Deletion / Q000276:immunology; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011134:Polysaccharides; D022562:Salmonella Vaccines; D014613:Vaccines, Attenuated; D015847:Interleukin-4; D007371:Interferon-gamma; C004275:colanic acid