ENHANCEMENT OF THE SPECIFIC MUCOSAL IGA RESPONSE IN-VIVO BY INTERLEUKIN-5 EXPRESSED BY AN ATTENUATED STRAIN OF SALMONELLA SEROTYPE DUBLIN

It has been shown that cytokines have potential as therapeutic adjuvan ts in vaccination. Interleukin-5 (IL-5) is a cytokine that regulates a ntibody production, in particular enhancing IgA production by activate d mucosal B cells. This study examined the expression of a cloned cyto kine gene encoding murine IL-5 (mIL-5) by an attenuated aroA strain (S L5631) of Salmonella serotype Dublin. The resulting strain, SL5631(pTR XFUS-mIL-5), expressed mIL-5 as a fusion with thioredoxin as demonstra ted by immunological and biological assays. When strain SL5631(pTRXFUS -mIL-5) was used as a live vaccine in BALB/c mice, it colonised and mu ltiplied at higher levels in spleens and livers than the strain carryi ng the empty plasmid. A reduction in invasiveness of SL5631(pTRXFUS-mI L-5) was observed in in-vitro invasion assays. Enhanced IgA response a gainst salmonella LPS in mucosal secretions and enhanced IgA and IgG r esponses were detected by ELISA and ELISPOT methods in sera of mice im munised with the strain expressing mIL-5. Results with IL-5-deficient mice showed that the enhanced IgA response was due to Salmonella-expre ssed mIL-5 rather than endogenous mIL-5.