Expression and delivery of tetanus toxin fragment C fused to the N-terminal domain of SipB enhances specific immune responses in mice.
Live attenuated bacteria can be used as a carrier for the delivery of foreign antigens to a host's immune system. The N-terminal domain of SipB, a translocon protein of the type III secretion system of Salmonella enterica serovar Typhimurium, is required for secretion and outer membrane localization. In the present study, vaccine plasmids for antigen delivery in which the non-toxic tetanus toxin fragment C (TTFC), which contains a T cell epitope, is fused to the N-terminal 160 amino acids of SipB were developed. It was found that the recombinant proteins are secreted into the culture media and localized to the bacterial surface. TTFC-specific antibody responses are significantly increased in mice orally immunized with attenuated S. Typhimurium BRD509 strains carrying TTFC delivery plasmids. When the TTFC delivery cassettes were introduced into a low copy vector, the plasmid was stably maintained in the BRD509 strain and induced an immune response to the TTFC antigen in mice. These results suggest that expression and delivery of heterologous antigens fused to the N-terminus of SipB enhance the induction of antigen-specific immune responses, and that the N-terminal domain of SipB can be used as a versatile delivery system for foreign antigens.
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
Jung Im
JI
Jang
Jin Seok
JS
Kim
Jeong Seon
JS
Eom
Hyeon Guk
HG
Kim
Bae Hoon
BH
Kim
Sangyong
S
Lim
Iel-Soo
IS
Bang
Yong Keun
YK
Park
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000917:Antibody Formation; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003470:Culture Media / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D022562:Salmonella Vaccines / Q000235:genetics / Q000276:immunology; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*; D013744:Tetanus Toxin / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D003470:Culture Media; D018984:Epitopes, T-Lymphocyte; D008565:Membrane Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D022562:Salmonella Vaccines; D013744:Tetanus Toxin; D014613:Vaccines, Attenuated; C094579:invasion protein B, Salmonella typhimurium; C040635:tetanus toxin fragment C