The Capsular Polysaccharide Vi from Salmonella Typhi Is a B1b Antigen

Vaccination with purified capsular polysaccharide Vi Ag from Salmonella typhi can protect against typhoid fever, although the mechanism for its efficacy is not clearly established. In this study, we have characterized the B cell response to this vaccine in wild-type and T cell–deficient mice. We show that immunization with typhoid vi polysaccharide vaccine rapidly induces proliferation in B1b peritoneal cells, but not in B1a cells or marginal zone B cells. This induction of B1b proliferation is concomitant with the detection of splenic Vi-specific Ab-secreting cells and protective Ab in Rag1-deficient B1b cell chimeras generated by adoptive transfer-induced specific Ab after Vi immunization. Furthermore, Ab derived from peritoneal B cells is sufficient to confer protection against Salmonella that express Vi Ag. Expression of Vi by Salmonella during infection did not inhibit the development of early Ab responses to non-Vi Ags. Despite this, the protection conferred by immunization of mice with porin proteins from Salmonella, which induce Ab-mediated protection, was reduced postinfection with Vi-expressing Salmonella, although protection was not totally abrogated. This work therefore suggests that, in mice, B1b cells contribute to the protection induced by Vi Ag, and targeting non-Vi Ags as subunit vaccines may offer an attractive strategy to augment current Vi-based vaccine strategies.

[1]  T. Manser,et al.  Characteristics of Borrelia hermsii infection in human hematopoietic stem cell-engrafted mice mirror those of human relapsing fever , 2011, Proceedings of the National Academy of Sciences.

[2]  S. Clare,et al.  A Salmonella Typhimurium-Typhi Genomic Chimera: A Model to Study Vi Polysaccharide Capsule Function In Vivo , 2011, PLoS pathogens.

[3]  J. Lakey,et al.  The structural orientation of antibody layers bound to engineered biosensor surfaces. , 2011, Biomaterials.

[4]  G. Dougan,et al.  Soluble flagellin, FliC, induces an Ag‐specific Th2 response, yet promotes T‐bet‐regulated Th1 clearance of Salmonella typhimurium infection , 2011, European journal of immunology.

[5]  G. Dougan,et al.  In Vivo Regulation of the Vi Antigen in Salmonella and Induction of Immune Responses with an In Vivo-Inducible Promoter , 2011, Infection and Immunity.

[6]  T. Rothstein,et al.  Human B1 cells in umbilical cord and adult peripheral blood express the novel phenotype CD20+CD27+CD43+CD70− , 2011, The Journal of Experimental Medicine.

[7]  T. Rothstein,et al.  Human B1 cells in umbilical cord and adult peripheral blood express the novel phenotype CD20+CD27+CD43+CD70− , 2011, The Journal of experimental medicine.

[8]  R. Rappuoli,et al.  Vi-CRM 197 as a new conjugate vaccine against Salmonella Typhi. , 2011, Vaccine.

[9]  S. Winter,et al.  The Vi Capsular Polysaccharide Prevents Complement Receptor 3-Mediated Clearance of Salmonella enterica Serotype Typhi , 2010, Infection and Immunity.

[10]  Anne K. Shriner,et al.  IL-7–Dependent B Lymphocytes Are Essential for the Anti-polysaccharide Response and Protective Immunity to Streptococcus pneumoniae , 2010, The Journal of Immunology.

[11]  J. Crump,et al.  Global trends in typhoid and paratyphoid Fever. , 2010, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[12]  J. Kearney,et al.  Generation of B Cell Memory to the Bacterial Polysaccharide α-1,3 Dextran1 , 2009, The Journal of Immunology.

[13]  K. Schwarz,et al.  Circulating CD21low B cells in common variable immunodeficiency resemble tissue homing, innate-like B cells , 2009, Proceedings of the National Academy of Sciences.

[14]  G. Dougan,et al.  The porin OmpD from nontyphoidal Salmonella is a key target for a protective B1b cell antibody response , 2009, Proceedings of the National Academy of Sciences.

[15]  J. Weill,et al.  Human marginal zone B cells. , 2009, Annual review of immunology.

[16]  S. Winter,et al.  Clinical pathogenesis of typhoid fever. , 2008, Journal of infection in developing countries.

[17]  S. Winter,et al.  The Vi‐capsule prevents Toll‐like receptor 4 recognition of Salmonella , 2008, Cellular microbiology.

[18]  J. Faro,et al.  Immune responses to polysaccharides: lessons from humans and mice. , 2008, Vaccine.

[19]  L. Leibovici,et al.  Typhoid fever vaccines: systematic review and meta-analysis of randomised controlled trials. , 2007, Vaccine.

[20]  I. Henderson,et al.  Salmonella Induces a Switched Antibody Response without Germinal Centers That Impedes the Extracellular Spread of Infection1 , 2007, The Journal of Immunology.

[21]  David G. Melvin,et al.  A recombineering based approach for high-throughput conditional knockout targeting vector construction , 2007, Nucleic acids research.

[22]  D. Favre,et al.  Vaccines against typhoid fever. , 2006, Vaccine.

[23]  K. Toellner,et al.  B cell clones that sustain long-term plasmablast growth in T-independent extrafollicular antibody responses. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[24]  I. Becker,et al.  Salmonella porins induce a sustained, lifelong specific bactericidal antibody memory response , 2006, Immunology.

[25]  A. Bäumler,et al.  Capsule-Mediated Immune Evasion: a New Hypothesis Explaining Aspects of Typhoid Fever Pathogenesis , 2006, Infection and Immunity.

[26]  K. Haas,et al.  B-1a and B-1b cells exhibit distinct developmental requirements and have unique functional roles in innate and adaptive immunity to S. pneumoniae. , 2005, Immunity.

[27]  S. Rubino,et al.  The Vi Capsular Antigen of Salmonella enterica Serotype Typhi Reduces Toll-Like Receptor-Dependent Interleukin-8 Expression in the Intestinal Mucosa , 2005, Infection and Immunity.

[28]  K. Toellner,et al.  Loss of CD154 impairs the Th2 extrafollicular plasma cell response but not early T cell proliferation and interleukin‐4 induction , 2004, Immunology.

[29]  T. Honjo,et al.  B1b lymphocytes confer T cell-independent long-lasting immunity. , 2004, Immunity.

[30]  J. Castañón-González,et al.  Induction of cellular immune response and anti-Salmonella enterica serovar typhi bactericidal antibodies in healthy volunteers by immunization with a vaccine candidate against typhoid fever. , 2004, Immunology letters.

[31]  H. Nikaido Molecular Basis of Bacterial Outer Membrane Permeability Revisited , 2003, Microbiology and Molecular Biology Reviews.

[32]  J. Kearney,et al.  Marginal zone and B1 B cells unite in the early response against T-independent blood-borne particulate antigens. , 2001, Immunity.

[33]  J. Shiloach,et al.  The efficacy of a Salmonella typhi Vi conjugate vaccine in two-to-five-year-old children. , 2001, The New England journal of medicine.

[34]  J. Schlessinger,et al.  Absence of marginal zone B cells in Pyk-2–deficient mice defines their role in the humoral response , 2000, Nature Immunology.

[35]  B. Wanner,et al.  One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[36]  M. Jenkins,et al.  Serovar Typhimurium Enterica Salmonella Virulent but Not Attenuated Antibody Is Required for Protection Against , 2000 .

[37]  G. Dougan,et al.  Igh-6−/−(B-Cell-Deficient) Mice Fail To Mount Solid Acquired Resistance to Oral Challenge with Virulent Salmonella enterica Serovar Typhimurium and Show Impaired Th1 T-Cell Responses toSalmonella Antigens , 2000, Infection and Immunity.

[38]  M. Falagas,et al.  Typhoid fever vaccines: a meta-analysis of studies on efficacy and toxicity , 1998, BMJ.

[39]  A. Pastore,et al.  Immunoglobulin-type domains of titin: same fold, different stability? , 1994, Biochemistry.

[40]  L. Herzenberg,et al.  Characteristics and Development of the Murine B‐lb (Ly‐1 B Sister) Cell Population , 1992, Annals of the New York Academy of Sciences.

[41]  S. Poppema,et al.  Immaturity of the human splenic marginal zone in infancy. Possible contribution to the deficient infant immune response. , 1989, Journal of immunology.

[42]  P. Amlot,et al.  IMPAIRED HUMAN ANTIBODY RESPONSE TO THE THYMUS-INDEPENDENT ANTIGEN, DNP-FICOLL, AFTER SPLENECTOMY Implications for Post-splenectomy Infections , 1985, The Lancet.

[43]  M. Apicella,et al.  Immunogenicity of gonococcal Gc2 polysaccharide: comparative studies with pneumococcal type III polysaccharide and Salmonella typhosa Vi antigen , 1978, Infection and immunity.

[44]  R. Germanier,et al.  Isolation and characterization of Gal E mutant Ty 21a of Salmonella typhi: a candidate strain for a live, oral typhoid vaccine. , 1975, The Journal of infectious diseases.

[45]  S. Pillai,et al.  Marginal zone B cells. , 2005, Annual review of immunology.

[46]  G. Dougan,et al.  Igh-6 2 / 2 (B-Cell-Deficient) Mice Fail To Mount Solid Acquired Resistance to Oral Challenge with Virulent Salmonella enterica Serovar Typhimurium and Show Impaired Th1 T-Cell Responses to Salmonella Antigens , 1999 .

[47]  J. Humphrey,et al.  Splenic dependence of the antibody response to thymus‐independent (TI‐2) antigens , 1985, European journal of immunology.

[48]  J. T. Ulrich,et al.  Development of a localized hemolysis-in-gel assay for Vi antigen: characterization of the Vi-specific PFC response of nude and normal mice. , 1977, Immunological communications.