Production of biologically active CXC chemokines by Lactococcus lactis: evaluation of its potential as a novel mucosal vaccine adjuvant.
Chemokines have been described as essential mediators in leukocytes migration to inflammatory sites and to secondary lymphoid organs. Mig and IP-10 are two CXC chemokines that recruit mononuclear cells in vivo and inhibit angiogenesis. In addition to their chemotactic roles, Mig and IP-10 have also an important role in the adaptative immune response. In this study, we asked whether a food-grade bacterium, Lactococcus lactis, is able to produce a fusion protein comprising Mig and IP-10 (Mig::IP-10). The activity of the recombinant Mig::IP-10 produced by the genetically engineered L. lactis (LL-Mig::IP-10) was confirmed in a murine spleen cells chemotaxis assay. Moreover, the adjuvant properties of LL-Mig::IP-10 strain were evaluated in mice by the co-expression of a model antigen, the human papillomavirus type 16 E7 protein. Our data show that LL-Mig::IP-10 can produce a genetic fusion of Mig::IP-10 biologically active. This recombinant strain represents a potential candidate for the development of new strategies for mucosal vaccination.
Cortes-Perez
Naima G
NG
INRA 0910, 78352 Jouy-en-Josas, France.
da Costa Medina
Luis F
LF
Lefèvre
François
F
Langella
Philippe
P
Bermúdez-Humarán
Luis G
LG
D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004269:DNA, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D018928:Immunity, Mucosal / Q000276:immunology*; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D013294:Lactococcus lactis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000235:genetics; D015202:Protein Engineering
D000276:Adjuvants, Immunologic; D019743:Chemokines, CXC; D004269:DNA, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G