Live Oral Typhoid Vaccine Ty21a Induces Cross-Reactive Humoral Immune Responses against Salmonella enterica Serovar Paratyphi A andS. Paratyphi B in Humans
ABSTRACTEnteric fever caused bySalmonella entericaserovar Paratyphi A infection has emerged as an important public health problem. Recognizing that in randomized controlled field trials oral immunization with attenuatedS. entericaserovar Typhi live vaccine Ty21a conferred significant cross-protection againstS. Paratyphi B but notS. 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 recognizeS. Typhi lipopolysaccharide (LPS). Cross-reactivity toS. Paratyphi A LPS was significantly lower than that toS. Paratyphi B LPS. ASC producing IgG and IgA that bind LPS from each of theseSalmonellaserovars 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 (BM) cells toS. Typhi LPS were significantly higher than those againstS. Paratyphi A or B LPS, with no differences observed betweenS. Paratyphi A and B. The response of IgA BMto outer membrane proteins (OMP) fromS. Typhi was significantly stronger than that to OMP ofS. Paratyphi A but similar to that to OMP ofS. Paratyphi B. The percentages of IgG or IgA BMresponders to LPS or OMP from theseSalmonellastrains were similar. Whereas cross-reactive humoral immune responses toS. Paratyphi A or B antigens are demonstrable following Ty21a immunization, they cannot explain the efficacy data gleaned from controlled field trials.