IBT/09 Evaluating the protective efficacy of Salmonella flagellin delivered via Fc receptor

Numerous studies have demonstrated that targeting antigen to Fc receptors (FcãRs) on APCs can enhance humoral and cellular immunity. The position of FcãRs as a gateway both to cellular and humoral aspects of the immune cascades make them potentially attractive candidates for directed immunotherapy. Salmonellosis is the disease complex of man and animals caused by various serovars of Salmonella enterica subspecies enterica. In present study, we have examined the effect of targeting an extracellular antigen from Salmonella i.e. flagellin to the immune system, by covalently coupling it to the Fc fragment of mouse IgG, on its efficacy for T cell stimulation in vitro and its immunogenicity for antibody production in vivo. We have compared the potency of free flagellin, flagellin coupled Fc fragment as well as a mixture of free flagellin plus Fc fragment in terms of humoral and cellular immune responses. The conjugate of flagellin with Fc stimulated the T cells proliferation and antibody production greater than other forms of the antigen over the entire time course of the response in addition to protection against a subsequent virulent Salmonella challenge. Finally, we conclude that FcãR-targeted immunogen enhances flagellin-specific IgG production and protection against subsequent infection in an IgG-dependent manner.