Mode of vaccine expression by salmonella dictates th cell response: Th2 cell precedes TH1 cell antienterotoxigenic e. coli (ETEC) fimbriae responses

Salmonella is an effective vehicle for vaccine delivery to mucosal inductive sites in the gastrointestinal tract. Previous work has shown that oral delivery of Salmonella expressing recombinant proteins typically induces CD4+ T helpers (Th) cell and IFN-γ-dominant pathways which result in serum IgG2a; paradoxically, strong mucosal IgA antibody responses are also induced. However, oral immunization with a Salmonella vector which stably secretes an ETEC colonization factor antigen I (CFA/I) resulted in serum IgGl and mucosal IgA anti-CFA/I antibody responses. After 3-4 weeks, the serum IgG subclass responses resulted in concurrent lgG2a antibodies. Changes in CFA/I-specific cytokine profiles were observed corroborating these immune profiles. Early in the immune response, the expression of IL-4 exceeded IFN-y by CFA/I-specific T cells. Elevated numbers of IL-5, IL-6, and IL-10 producing T cells were also evident. During the late phase, minimal IL-4 and no IL-5 production was obtained; however, an increase in the expression of IFN-y producing T cells was evident. These results show that it is possible to construct Salmonella vectors to elicit the desired immune response for optimal vaccine efficacy.