title: Specific and cross-reactive immune response to oral Salmonella Typhi Ty21a and parenteral Vi capsular polysaccharide typhoid vaccines administered concomitantly.
abstract: BACKGROUND
  Since protective efficacy of the current typhoid vaccines-oral whole-cell Salmonella Typhi Ty21a and parenteral Vi-capsular polysaccharide preparation-is not optimal, and no vaccines are available against paratyphoid or non-typhoidal Salmonella (NTS) serotypes, new approaches deserve to be explored. The immunological mechanisms elicited by the two typhoid vaccines are mainly targeted against different structures. We studied whether these vaccines would enhance S. Typhi-specific immune response and cross-reactivity against other Salmonellae, if administered concomitantly.
  
  
  METHODS
  Volunteers were immunized simultaneously with Ty21a and Vi vaccines (Ty21a+Vi group) or with either of the two singly (Ty21a and Vi groups). All volunteers were investigated for circulating specific and cross-reactive plasmablasts, identified by ELISPOT as IgA, IgG or IgM antibody-secreting cells (ASC) reactive with S. Typhi, S. Paratyphi A/B/C, or selected NTS serotypes (S. Enteritidis, S. Typhimurium).
  
  
  RESULTS
  In the Ty21a+Vi group, no specific or cross-reactive plasmablasts were detected before vaccination. After vaccination, the number of S. Typhi-specific plasmablasts (878 ASC/10(6) PBMC, 95%CI 554-1201) proved higher than in the Ty21a (339 ASC/10(6) PBMC; p<0.001) and Vi (149 ASC/10(6) PBMC; p<0.001) groups. Likewise, cross-reactive responses in the Ty21a+Vi group were higher than in the Ty21a and Vi groups (Ty21a+Vi vs Ty21a: ASC against S. Paratyphi A/B, S. Enteritidis and S. Typhimurium p<0.05, against S. Paratyphi C p<0.01; Ty21a+Vi vs Vi: against S. Paratyphi C not significant, others p<0.0001). A gut-directed homing profile was seen among O antigen-specific and a systemic one among Vi antigen-specific plasmablasts.
  
  
  CONCLUSIONS
  Concomitant administration of Ty21a and Vi vaccines is well tolerated and induces an additive immune response to the two vaccines. Thus it enhances the magnitude of both typhoid-specific plasmablast responses and those cross-reacting with paratyphoid and most important NTS serotypes. The data encourage concomitant use of Ty21 and Vi vaccines for those at risk.
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, POB 21, 00014 Helsinki, Finland; Department of Medicine, Division of Infectious Diseases, Helsinki University Hospital POB 348, 00029 Helsinki, Finland.
authors.forename: Sari H
authors.initials: SH
authors.lastname: Pakkanen
authors.affiliation: Department of Medical Microbiology and Immunology, University of Turku, Kiinamyllynkatu 13, 20520 Turku, Finland.
authors.forename: Jussi M
authors.initials: JM
authors.lastname: Kantele
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, POB 21, 00014 Helsinki, Finland.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Savolainen
authors.affiliation: Karolinska Institutet, Department of Medicine/Solna, Unit for Infectious Diseases, Stockholm, Sweden; Centre for Clinical Research, Sörmland County Council, Eskilstuna, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Rombo
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, POB 21, 00014 Helsinki, Finland; Department of Medicine, Division of Infectious Diseases, Helsinki University Hospital POB 348, 00029 Helsinki, Finland; Department of Medicine, University of Helsinki, POB 20, 00014 Helsinki, Finland; Aava Travel Clinic, Medical Centre Aava, Helsinki, Finland. Electronic address: anu.kantele@hus.fi.
authors.forename: Anu
authors.initials: A
authors.lastname: Kantele
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000096:biosynthesis*; D000921:Antibody-Producing Cells / Q000276:immunology; D003429:Cross Reactions; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000276:immunology; D012477:Salmonella enteritidis / Q000276:immunology; D012482:Salmonella paratyphi A / Q000276:immunology; D012485:Salmonella typhi / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology; D014435:Typhoid Fever / Q000276:immunology / Q000517:prevention & control*; D014436:Typhoid-Paratyphoid Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011135:Polysaccharides, Bacterial; D014436:Typhoid-Paratyphoid Vaccines; C054154:capsular polysaccharide, Salmonella
keywords: Antibody-secreting cell; ClinicalTrials.gov NCT02121145; Cross-reactive; ELISPOT; Homing; Non-typhoid Salmonella; Paratyphoid fever; S. Paratyphi; Salmonella Typhi; Salmonella Typhi Ty21a; Salmonella gastroenteritis; Typherix; Typhim Vi; Typhoid fever; Vi polysaccharide; Vivotif