title: Cross-reactive gut-directed immune response against Salmonella enterica serovar Paratyphi A and B in typhoid fever and after oral Ty21a typhoid vaccination.
abstract: BACKGROUND
  There are no vaccines against paratyphoid fever in clinical use. The disease has become more wide-spread and there is a growing problem of antibiotic resistance among the strains. Previous reports suggest that the oral live Salmonella Typhi Ty21a-vaccine confers protection against paratyphoid B fever. Data on efficacy against paratyphoid A fever are somewhat contentious. The present study investigated the immunological basis for such efficacy reports at a single-cell level: plasmablasts (identified as antibody-secreting cells, ASC) were studied for secretion of antibodies cross-reactive with Salmonella Paratyphi in the circulation of patients with enteric fever and of volunteers vaccinated with Ty21a.
  
  
  METHODS
  Thirty volunteers immunized with Ty21a and five patients with enteric fever were investigated for Salmonella Typhi and Salmonella Paratyphi A/B/C-specific circulating plasmablasts. PBMC were sorted by their expression of homing receptors (HR) for the intestine (α4β7), peripheral lymph node (l-selectin) and skin (CLA) and typhoid- and paratyphoid-specific plasmablasts were enumerated with ELISPOT.
  
  
  RESULTS
  Before vaccination, no cross-reactive ASC were found in the volunteers. In addition to the Salmonella Typhi-specific response, a significant cross-reactive immune response was mounted against Salmonella Paratyphi A and B both in the patients and the vaccinees. The magnitude of the response increased in the order Salmonella Paratyphi A (median 30 ASC/10(6) PBMC)→Salmonella Paratyphi B (median 81)→Salmonella Typhi (median 301) in the vaccinees. Both in patients and in vaccinees, the homing receptor (HR) selection favored homing to the gut, indicating a humoral intestinal immune response.
  
  
  CONCLUSIONS
  These immunological data provide evidence consistent with previous reports describing certain levels of cross-protective efficacy of Ty21a against paratyphoid fever. Controlled studies are needed to evaluate cross-protective efficacy. In the current situation where paratyphoid fever is emerging and no vaccines are available, any level of cross-protective capacity is valuable.
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, POB 21, 00014 University of Helsinki, Helsinki, Finland. sari.pakkanen@helsinki.fi
authors.forename: Sari H
authors.initials: SH
authors.lastname: Pakkanen
authors.forename: Jussi M
authors.initials: JM
authors.lastname: Kantele
authors.forename: Anu
authors.initials: A
authors.lastname: Kantele
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000921:Antibody-Producing Cells / Q000276:immunology*; D056738:Cross Protection / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal; D016023:Integrins / Q000378:metabolism; D007422:Intestines / Q000276:immunology; D019041:L-Selectin / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010284:Paratyphoid Fever / Q000276:immunology / Q000517:prevention & control*; D011135:Polysaccharides, Bacterial / Q000276:immunology / Q000627:therapeutic use*; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D012482:Salmonella paratyphi A / Q000276:immunology / Q000472:pathogenicity*; D012867:Skin / Q000276:immunology; D014435:Typhoid Fever / Q000276:immunology / Q000517:prevention & control; D014436:Typhoid-Paratyphoid Vaccines / Q000276:immunology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D016023:Integrins; D011135:Polysaccharides, Bacterial; D016201:Receptors, Lymphocyte Homing; C072772:Ty21a typhoid vaccine; D014436:Typhoid-Paratyphoid Vaccines; C071777:integrin alpha4beta7; D019041:L-Selectin