Mucosal and cellular immune responses elicited by recombinant Lactococcus lactis strains expressing tetanus toxin fragment C.
The mucosal and cellular responses of mice were studied, following mucosal-route administration of recombinant Lactococcus lactis expressing tetanus toxin fragment C (TTFC), which is a known immunogen protective against tetanus. A TTFC-specific T-cell response with a mixed profile of T-helper (Th) subset-associated cytokines was elicited in the intestine, with a Th2 bias characteristic of a mucosal response. These results correlated with the humoral response, where equivalent titers of anti-TTFC immunoglobulin G1 (IgG1) and IgG2a in serum were accompanied by an elevated IgA-specific response at more than one mucosal site. The route of vaccination had an important role in determining the immune response phenotype, as evidenced by the fact that an IgG1-biased subclass profile was obtained when lactococci were administered parenterally. Stimulation of splenic or mesenteric lymph node cells with lactococci resulted in their proliferation and the secretion of gamma interferon via antigen-specific and innate immune mechanisms. The data therefore provide further evidence of the potential of recombinant lactococcal vaccines for inducing systemic and mucosal immune responses.
Robinson
K
K
Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom. Karen.robinson@nottingham.ac.uk
Chamberlain
L M
LM
Lopez
M C
MC
Rush
C M
CM
Marcotte
H
H
Le Page
R W F
RW
Wells
J M
JM
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D005260:Female; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D007274:Injections, Intraperitoneal; D013294:Lactococcus lactis / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013270:Stomach; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013744:Tetanus Toxin / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics
D000907:Antibodies, Bacterial; D010446:Peptide Fragments; D011994:Recombinant Proteins; D013744:Tetanus Toxin; D014614:Vaccines, Synthetic; C040635:tetanus toxin fragment C