Cell mediated immune responses elicited in volunteers following immunization with candidate live oral Salmonella enterica serovar Paratyphi A attenuated vaccine strain CVD 1902

Abstract

The incidence of Salmonella enterica serovar Paratyphi A (PA) infection is on the rise and no licensed vaccines are available. We evaluated cell mediated immune (CMI) responses elicited in volunteers following immunization with a single dose (10⁹ or 10¹⁰ cfu) of a novel attenuated live oral PA-vaccine strain (CVD 1902). Results showed increases in PA-lipopolysaccharide-specific IgG- and/or IgA B-memory cells and production of IFN-γ, TNF-α, IL-10, IL-23 and RANTES following stimulation with PA-antigens by peripheral blood mononuclear cells obtained 28 days post immunization. Flow cytometry assays revealed that vaccine elicited PA-specific CD8+ and/or CD4+ T effector/memory cells were predominantly multifunctional concomitantly expressing CD107a and/or producing IFN-γ, TNF-α and/or IL-2. Similar proportions of these MF cells expressed, or not, the gut homing marker integrin α4β7. The results suggest that immunization with CVD 1902 elicits CMI responses against PA supporting its further evaluation as a potential vaccine candidate against paratyphoid A fever.

Keywords: Cell Mediated immunity; Human; Multifunctional; S. Paratyphi A; Salmonella; Vaccines.