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 adjuvants in vaccination. Interleukin-5 (IL-5) is a cytokine that regulates antibody production, in particular enhancing IgA production by activated mucosal B cells. This study examined the expression of a cloned cytokine gene encoding murine IL-5 (mIL-5) by an attenuated aroA strain (SL5631) of Salmonella serotype Dublin. The resulting strain, SL5631(pTRXFUS-mIL-5), expressed mIL-5 as a fusion with thioredoxin as demonstrated by immunological and biological assays. When strain SL5631(pTRXFUS-mIL-5) was used as a live vaccine in BALB/c mice, it colonised and multiplied at higher levels in spleens and livers than the strain carrying the empty plasmid. A reduction in invasiveness of SL5631(pTRXFUS-mIL-5) was observed in in-vitro invasion assays. Enhanced IgA response against salmonella LPS in mucosal secretions and enhanced IgA and IgG responses were detected by ELISA and ELISPOT methods in sera of mice immunised with the strain expressing mIL-5. Results with IL-5-deficient mice showed that the enhanced IgA response was due to Salmonella-expressed mIL-5 rather than endogenous mIL-5.
Whittle
B L
BL
Division of Biochemistry and Molecular Biology, Faculty of Science, Canberra, Australia.
Smith
R M
RM
Matthaei
K I
KI
Young
I G
IG
Verma
N K
NK
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001428:Bacterial Vaccines / Q000276:immunology; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D015848:Interleukin-5 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010957:Plasmids; D012475:Salmonella / Q000235:genetics / Q000276:immunology*; D012481:Salmonella Infections, Animal / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D015848:Interleukin-5; D008070:Lipopolysaccharides; D014613:Vaccines, Attenuated