title: Live oral typhoid vaccine Ty21a induces cross-reactive humoral immune responses against Salmonella enterica serovar Paratyphi A and S. Paratyphi B in humans.
abstract: Enteric fever caused by Salmonella enterica serovar Paratyphi A infection has emerged as an important public health problem. Recognizing that in randomized controlled field trials oral immunization with attenuated S. enterica serovar Typhi live vaccine Ty21a conferred significant cross-protection against S. Paratyphi B but not S. Paratyphi A disease, we undertook a clinical study to ascertain whether humoral immune responses could explain the field trial results. Ty21a immunization of adult residents of Maryland elicited predominantly IgA antibody-secreting cells (ASC) that recognize S. Typhi lipopolysaccharide (LPS). Cross-reactivity to S. Paratyphi A LPS was significantly lower than that to S. Paratyphi B LPS. ASC producing IgG and IgA that bind LPS from each of these Salmonella serovars expressed CD27 and integrin α4β7 (gut homing), with a significant proportion coexpressing CD62L (secondary lymphoid tissue homing). No significant differences were observed in serum antibody against LPS of the different serovars. Levels of IgA B memory (B(M)) cells to S. Typhi LPS were significantly higher than those against S. Paratyphi A or B LPS, with no differences observed between S. Paratyphi A and B. The response of IgA B(M) to outer membrane proteins (OMP) from S. Typhi was significantly stronger than that to OMP of S. Paratyphi A but similar to that to OMP of S. Paratyphi B. The percentages of IgG or IgA B(M) responders to LPS or OMP from these Salmonella strains were similar. Whereas cross-reactive humoral immune responses to S. Paratyphi A or B antigens are demonstrable following Ty21a immunization, they cannot explain the efficacy data gleaned from controlled field trials.
authors.affiliation: Department of Pediatrics, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Rezwanul
authors.initials: R
authors.lastname: Wahid
authors.forename: Raphael
authors.initials: R
authors.lastname: Simon
authors.forename: Shah J
authors.initials: SJ
authors.lastname: Zafar
authors.forename: Myron M
authors.initials: MM
authors.lastname: Levine
authors.forename: Marcelo B
authors.initials: MB
authors.lastname: Sztein
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D056738:Cross Protection; D003429:Cross Reactions; D005260:Female; D006805:Human Experimentation; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008396:Maryland; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012482:Salmonella paratyphi A / Q000276:immunology*; D012484:Salmonella paratyphi B / Q000276:immunology*; D012485:Salmonella typhi / Q000276:immunology; D014436:Typhoid-Paratyphoid Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D014436:Typhoid-Paratyphoid Vaccines; D014613:Vaccines, Attenuated