Recognition of a hepatitis B virus nucleocapsid T-cell epitope expressed as a fusion protein with the subunit B of Escherichia coli heat labile enterotoxin in attenuated salmonellae.
Two overlapping T-cell sites of the nucleocapsid antigen (HBc) of Hepatitis B Virus (HBV) (amino acids (aa) 120-140) and a B-cell epitope of the pre-S(2) region of the HBV surface antigen (aa 133-140) were expressed as a fusion protein with the subunit B of Escherichia coli heat labile enterotoxin (LT-B) in attenuated salmonellae (aroA Salmonella dublin SL1438). When Balb/c (haplotype H-2d) mice were fed salmonellae expressing LT-B or the LT-B/HBV fusion protein they developed serum IgG anti-LT-B antibodies and splenic cells reactive to LT-B. C57BL/10 (H-2b), in contrast, showed anti-LT-B antibody titres, but no splenic cell priming to LT-B. Neither in Balb/c nor in C57BL/10 mice could an antibody response to the fused HBV antibody binding site be demonstrated. In C57BL/10, however, an HBc T-cell epitope fused to LT-B primed a splenic cell response to an analogous synthetic peptide (HBc aa 121-145) in four out of five mice after three oral immunizations. This is the first description of the priming of a cellular immune response to a defined heterologous epitope expressed in attenuated salmonellae and delivered by the oral route.
Schödel
F
F
Max-Planck-Institut für Biochemie, Martinsried, FRG.
Enders
G
G
Jung
M C
MC
Will
H
H
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D002213:Capsid / Q000235:genetics / Q000276:immunology*; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D029968:Escherichia coli Proteins; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D012483:Salmonella Phages / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology / Q000494:pharmacology; D014614:Vaccines, Synthetic / Q000276:immunology / Q000494:pharmacology; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology
D000956:Antigens, Viral; D001427:Bacterial Toxins; D004768:Enterotoxins; D000939:Epitopes; D029968:Escherichia coli Proteins; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014758:Viral Core Proteins; D014760:Viral Fusion Proteins; C027538:heat-labile enterotoxin, E coli