title: Cross-reactive immune response elicited by parenteral Vi polysaccharide typhoid vaccine against non-typhoid Salmonellae.
abstract: BACKGROUND
  Despite 155000 deaths and over 90 million cases - and the current emergence of antimicrobial resistance - no vaccines are available against non-typhoid Salmonellae (NTS). We recently presented immunological arguments for using the oral Salmonella Typhi Ty21a as surrogate vaccine against NTS strains: Ty21a elicits intestinal antibodies against typhoidal O-9,12 antigen, and numerous NTS strains share one or both of these structures with S. Typhi. The Vi polysaccharide vaccine can, presumably because of contaminating typhoidal lipopolysaccharide, also elicit a humoral response to O-9,12, although a lower one in magnitude than the Ty21a. In this study, the Vi vaccine was explored for cross-reactive immune response to various NTS strains, and compared to that elicited by the Ty21a vaccine.
  
  
  METHODS
  Volunteers immunized with the Vi polysaccharide (Typherix(®); n=25) were investigated for circulating plasmablasts secreting antibodies reactive with six NTS serotypes. The results were compared to those for 25 age- and gender-matched volunteers vaccinated with Ty21a (Vivotif(®)), as partly presented in our previous study. The cross-reactive plasmablasts elicited by the Vi vaccine were also analyzed for homing receptor expressions.
  
  
  RESULTS
  49 out of 50 vaccinees showed a cross-reactive plasmablast response against S. Enteritidis sharing both O-9 and O-12 antigens with S. Typhi (mean: 95%CI 37: 19-55 and 363: 234-493 plasmablasts/10(6) PBMC in the Vi and the Ty21a group, respectively). The response against strains only sharing O-12 was weaker (22: 8-38 and 222: 105-338 against S. Typhimurium). Strains without typhoidal O-antigens generated no significant reactivity. The cross-reactive plasmablasts elicited by the Vi vaccine had systemic homing properties.
  
  
  CONCLUSIONS
  The Vi vaccine elicited an immune response cross-reactive with several NTS strains. This response was lower than that in Ty21a-vaccinated volunteers. The clinical significance of these responses deserves further research with respect to both gastrointestinal and invasive NTS (iNTS) disease.
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, POB 21, 00014 University of Helsinki, Helsinki, Finland; Department of Medicine, Division of Infectious Diseases, POB 348, 00029 Helsinki University Hospital, Helsinki, Finland. Electronic address: sari.pakkanen@helsinki.fi.
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. Electronic address: jussi.kantele@utu.fi.
authors.forename: Jussi M
authors.initials: JM
authors.lastname: Kantele
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Herzog
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, POB 21, 00014 University of Helsinki, Helsinki, Finland; Department of Medicine, Division of Infectious Diseases, POB 348, 00029 Helsinki University Hospital, Helsinki, Finland; Institute of Clinical Medicine, Department of Medicine, POB 20, 00014 University of Helsinki, Helsinki, Finland. Electronic address: anu.kantele@hus.fi.
authors.forename: Anu
authors.initials: A
authors.lastname: Kantele
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D000917:Antibody Formation; D003429:Cross Reactions / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019081:O Antigens / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D012475:Salmonella; D014435:Typhoid Fever / Q000517:prevention & control*; D014436:Typhoid-Paratyphoid Vaccines / Q000276:immunology*; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D019081:O Antigens; D011135:Polysaccharides, Bacterial; C072772:Ty21a typhoid vaccine; D014436:Typhoid-Paratyphoid Vaccines; C057664:Vi polysaccharide vaccine, typhoid
keywords: ALS; ASC; Antibody-secreting cell; CLA; Cross-reactive; HR; NTS; Non-typhoid Salmonella; PBMC; PBS; Salmonella Typhi Ty21a; Typherix; Vi polysaccharide; antibodies in lymphocyte supernatants; antibody-secreting cell; cutaneous lymphocyte antigen; homing receptor; iNTS; invasive non-typhoid Salmonella; non-typhoid Salmonella; peripheral blood mononuclear cells; phosphate buffered saline