Development of a Mucosal Complex Vaccine against OralSalmonellaInfection in Mice

Abstract

We examined the immunogenicity of a Salmonella enterica complex vaccine (CV), consisting of flagellin and polysome purified from serotype Typhimurium LT2. CV plus cholera toxin (CT), in three oral doses given at 7‐day intervals, conferred complete protection on C57BL/6 mice against lethal oral infection with a wild‐type strain. It elicited mucosal IgA>IgG2a>IgG1 and systemic IgG2a>IgG1>IgA antibodies to flagellin and polysome, and delayed footpad response (DFR) to both antigens. In Peyer's patches (PPs) and lamina propria (LP), IgA was produced under a Th1‐dominant environment; CD4T cells from produced interleukin (IL)‐2, interferon (IFN)‐γ, and IL‐10 by stimulation with salmonella extract. On the same protocol, flagellin plus CT induced flagellin‐specific mucosal and systemic IgA and IgG1 antibodies, CD4T cells producing IL‐10 and IFN‐γ in PPs and LP, and only minimal levels of flagellin‐specific DFR. Polysome plus CT induced polysome‐specific mucosal and systemic IgG2a in addition to IgG1 and IgA antibodies, CD4₊T cells producing IFN‐γ and IL‐2 in PPs and LP, and polysome‐specific DFR. These two vaccines, however, conferred at most 50–60% survival rates. Our results suggest that polysomes in CV provide effective adjuvant activity for the induction of both mucosal and systemic Th1‐biased responses toward flagellin.