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.

Materials and 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.

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.