Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Mucosal Immune Response and Adjuvant Activity of Genetically Fused Escherichia coli Heat-Labile Toxin B Subunit

  • Lee, Yung-Gi (Department of Biology, Chungnam National University, Bio Research Group, KT＆G Central Research Institute) ;
  • Kang, Hyung-Sik (School of Biological Sciences and Technology, Biotechnology Research Institute, Chonnam National University) ;
  • Lee, Cheong-Ho (Bio Research Group, KT＆G Central Research Institute) ;
  • Paik, Sang-Gi (Department of Biology, Chungnam National University)
  • Published : 2004.06.01
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Abstract

Although the E. coli heat-labile enterotoxin B subunit (LTB) is known to be a potent mucosal adjuvant towards co-administrated unrelated antigens and immunoregulator in T-helper 1-type-mediated autoimmune diseases, a more efficient and useful LTB is still required for prospective vaccine adjuvants. To determine whether a novel chimeric LTB subunit would produce an enhanced mucosal adjuvant activity and immune response, a number of LTB subunits were genetically fused with chimeric proteins using the epitope genes of the envelope glycoprotein E2 (gp51-54) from the classical swine fever virus (CSFV). It was found that the total serum immunoglobulin (Ig) levels of BALB/c mice orally immunized with chimeric proteins containing an N-terminal linked LTB subunit (LE1, LE2, and LE3) were higher than those of mice immunized with LTB, E2 epitope, and chimeric proteins that contained a C-terminal linked LTB subunit. In particular, immunization with LE1 markedly increased both the total serum Ig and fecal IgA level compared to immunization with LTB or the E2 epitope. Accordingly, the current results demonstrated that the LTB subunit in a chimeric protein exhibited a strong mucosal adjuvant effect as a carrier molecule, while the chimeric protein containing the LTB subunit stimulated the mucosal immune system by mediating the induction of antigen-specific serum Ig and mucosal IgA. Consequently, an LE1-mediated mucosal response may contribute to the development of effective antidiarrhea vaccine adjuvants.

Keywords

References

  1. Infect. Immun. v.65 Intranasal vaccination of humans with recombinant cholera toxin B subunit induces systemic and local antibody responses in the upper respiratory tract and the vagina Bergquist,C.;E.L.Johansson;T.Lagergard;J.Holmgren;A.Rudin
  2. Infect. Immun. v.61 Reduction in oral immunogenicity of cholera toxin B subunit by N-terminal peptide addition Dertzbaugh,M.T.;C.O.Elson
  3. Infect. Immun. v.56 Comparison of the carbohydrate-binding specificities of cholera toxin and Escherichia heat-labile specificitiesof cholera toxin and Escherichia coli heat-labile enterotoxin LTh-I, LT-IIa and LT-IIb Fukanta,S.;J.L.Magnani;E.M.Twiddy;R.K.Holmes;V.Ginsberg
  4. Immunology v.94 Role of GM1 binding in the mucosal immunogenicity and adjuvant of the Escherichia coli heat-labile enterotoxin and its B subunit de Hann,L.;W.R.V;erweijI.K.Feil;M.Holtrop;W.G.J.Hol;E.Agsteribbe;J.Wilschut https://doi.org/10.1046/j.1365-2567.1998.00535.x
  5. Infect. Immun. v.38 Rabbit intestinal glycoprotein receptor for Escherichia coli heat-labile enterotoxin lacking affinity for cholera toxin Holmgren,J.;P.Freedman;M.Lindblad;A.M.Svennerholm;L.Svennerholm
  6. J. Virol. v.67 Glycoprotein E1 of hog cholera virus expressed in insect-cells protects swine from hog cholera Hulst,M.M.;D.F.Westra;G.Wensvoort;R.J.M.Moormann
  7. Arch. Virol. v.140 Comparison of the entire nucleotide and deduced amino acid sequences of the attenuated hog cholera vaccine strain GPE-and the wild-type parental strain ALD Ishikawa,K.;H.Nagai;K.Katayama;M.Tsutsui;K.Tanabayashi;K.Takeuchi;M.Hishiyama;A.Saitoh;M.Takagi;K.Gotoh;M.Muramatsu;A.Yamada https://doi.org/10.1007/BF01322665
  8. Nature v.227 Cleavage of structural proteins during the assembly of the bacteriophage T4 Laemmli,U.K. https://doi.org/10.1038/227680a0
  9. J. Immunol. v.155 Mucosal adjuvant effect of cholera toxin in mice results from induction of T helper 2 (Th2) cells and IL-4 Mariano,M.;H.F.Staats;T.Horoi
  10. J. Immunol. v.133 Cholera toxin B subunit as a carrier protein to stimulate a mucosal immune response McKenzie,S.J.;J.H.Halsey
  11. Vaccine v.11 Current progress in the development of the B subnits of cholera toxin and Escherichia coli heat-labile enterotoxin as carriers for the oral delivery of heterologous antigens and epitopes Nashar,T.O.;T.Amin;A.Marcello;T.R.Hirst https://doi.org/10.1016/0264-410X(93)90023-Q
  12. Int. Immunol. v.8 Cross-linking of cell surface ganglioside GM1 induces the selective apoptosis of mature CD8+ T-lymphocytes Nashar,T.O.;N.A.Williams;T.R.Hirst;T.O.Nashar https://doi.org/10.1093/intimm/8.5.731
  13. Immunology v.91 Modulation of B-cell activation by the B subunit of Escherichia coli enterotoxin: Receptor interaction upregulates MHC class II, B7, CD40, CD25 and ICAM-1 Nashar,T.O.;T.R.Hirst;N.A.Williams https://doi.org/10.1046/j.1365-2567.1997.00291.x
  14. J. Microbiol. Biotechnol. v.12 Simple purification of Shiga toxin B chain from recombinant Escherichia coli Oh,Y.P.;S.T.Jeong;D.W.Kim;E.C.Kim;K.H.Yoon
  15. J. Virol. v.68 Antigenic structure of envelope glycoprotein E1 of hog cholera virus van Rijn,P.A.;G.K.Miedema;G.Wensvoort;H.G.P.van Gennip;R.J.M.Moormann
  16. J. Gen. Virol. v.77 Classical swine one structural antigenic unit protects pigs from lethal CSFV challenge van Rijn,P.A.;A.Bosser;G.Wensvoort;R.J.M.Moormann https://doi.org/10.1099/0022-1317-77-11-2737
  17. J. Biol. Chem. v.270 Kinetics of acid-mediated disassembly of the B subunit pentamer of Escherichia coli heat-labile enterotoxin Ruddock,L.W.;S.P.Ruston;S.M.Kelly;N.C.Price;R.B.Freedman;T.R.Hirst https://doi.org/10.1074/jbc.270.50.29953
  18. Virus Genes v.10 Baculovirus expression and affinity purification of protein E2 of classical swine fever virus strain Alfort/187 Ruggli,N.;C.Moser;D.Mitchell;M.Hofmann;J.D.Tratschin https://doi.org/10.1007/BF01702592
  19. J. Bacteriol. v.169 Alterations at the carboxyl terminus change assembly and secretion properties of the B subunit Escherichia coli heat-labile enterotoxin Sandkvist,M.;T.R.Hirst;M.Bagdasarian https://doi.org/10.1128/jb.169.10.4570-4576.1987
  20. Gene v.99 Synthesis in vibrio cholerea and secretion of hepatitis B virus antigens fused to Escherichia coli heat-labile enterotoxin subunit B Schodel,F.;H.Will;S.Johansson;J.Sanchez;J.Holmgren https://doi.org/10.1016/0378-1119(91)90135-X
  21. Crit. Rev. Immunol. v.15 The mucosal adjuvant activities of ADP-ribosylating bacterial enterotoxins Snider,D.P. https://doi.org/10.1615/CritRevImmunol.v15.i3-4.70
  22. J. Microbiol. Biotechnol. v.12 A novel protein to bind HCV core protein: The carboxyl terminus-truncated $core_{120}$ protein of HCV interacts with E7 antigen of human papilloma virus type 18 So,K.Y.;H.J.Lee;K.I.Kang;H.Y.Lee;K.Lim;S.G.Paik;J.K.Ahn;C.J.Kim;C.K.Lee;Y.S.Kim
  23. J. Infect. Dis. v.173 Mechanism of mucosal immunogenicity and adjuvancity of Escherichia coli heat-labile enterotoxin Takahashi,I.;H.Mariano;H.Kiyono;R.J.Jackson;I.Nakagawa;K.Fujihashi;S.Hamada;J.D.Clements;K.L.Bost;J.R.McGhee https://doi.org/10.1093/infdis/173.3.627
  24. J. Virol. v.65 Hog cholera virus: Molecular composition of virious from a pestivirus Thiel,H.J.;R.Stark;E.Weiland;T.Rumenapf;G.Meyers
  25. Infect. Immun. v.90 Glycosphigolipids as novel targets for T-cell supression by the B subnit of recombination heat-labile enterotoxin Truitt,R.I.;C.Hanke;J.Radke;R.Mueller;J.T.Barbiert
  26. Vaccine v.16 Mucosal immunoadjuvant activity of recombinant Escherichia coli heat-labile enterotoxin and its B subunit: Induction of systemic IgG and secretory IgA response in mice by intranasal immunization with influenza virus surface antigen Verweij,W.R.;de Hann;M.Holtrop;E.Agsteribbe;R.Brands;G.J.M.van Scharrenburg;J.Wilshut https://doi.org/10.1016/S0264-410X(98)00076-0
  27. Virus Taxonomy. Proceddings of the 6th Report of the International Committee on Taxonomy of Viruses Flaviviridae, Wengler,G.;D.W.Bradley;M.S.Colett;F.X.Heinz;R.W.Schlesinger;J.H.Strauss;F.A.Murphy(ed.);C.M.Fauquet(ed.);D.H.L.Bishop(ed.);S.A.Ghabrial(ed.);A.W.Jarvis(ed.);G.P.Martelli(ed.);M.A.Mayo(ed.);M.D.Summers(ed.)
  28. Infect. Immun. v.61 Induction of mucosal immunity by intranasal application of a streptococcal surface protein antigen with the cholera toxin B subunit Wu,H.Y.;M.W.Russell
  29. J. Virol. v.65 Live attenuated pseudorabies virus expressing envelope glycoprotein E1 of hog cholera virus protects swine against both pseudorabies and hog cholera van Zijl,M.;G.Wensvoort;E.P.de Kluyver;M.M.Hulst;H.van der Gulden;A.L.J.Gielkens;A.Berns;R.J.M.Moormann