Loss Of Sialic Acid Binding Domain Redirects Protein Sigma 1 To Enhance M Cell-Directed Vaccination

Ovalbumin (OVA) genetically fused to protein sigma 1 (p sigma 1) results in tolerance to both OVA and p sigma 1. P sigma 1 binds in a multi-step fashion, involving both protein-and carbohydrate-based receptors. To assess the relative p sigma 1 components responsible for inducing tolerance and the importance of its sialic binding domain (SABD) for immunization, modified OVA-p sigma 1, termed OVA-p sigma 1(short), was deleted of its SABD, but with its M cell targeting moiety intact, and was found to be immunostimulatory and enhanced CD4(+) and CD8(+) T cell proliferation. When used to nasally immunize mice given with and without cholera toxin (CT) adjuvant, elevated SIgA and serum IgG responses were induced, and OVA-p sigma 1(s) was more efficient for immunization than native OVA+CT. The immune antibodies (Abs) were derived from elevated Ab-forming cells in the upper respiratory tissues and submaxillary glands and were supported by mixed Th cell responses. Thus, these studies show that p sigma 1(s) can be fused to vaccines to effectively elicit improved SIgA responses.