Advertisement

Journal of Biomedical Science

, Volume 12, Issue 2, pp 279–287 | Cite as

Enhancement of DNA vaccine potency through linkage of antigen gene to ER chaperone molecules, ER-60, tapasin, and calnexin

  • Cheng-Tao Lin
  • Ting-Chang Chang
  • Angel Chao
  • Elizabeth Dzeng
  • Yung-Kuei Soong
  • Chien-Fu Hung
  • Chyong-Huey Lai
Article

Abstract

DNA vaccines have emerged as an attractive approach for generating antigen-specific immunotherapy. Strategies that enhance antigen presentation may potentially be used to enhance DNA vaccine potency. Previous experiments showed that chimeric DNA vaccines utilizing endoplasmic reticulum (ER) chaperone molecules, such as Calreticulin (CRT), linked to an antigen were capable of generating antigen-specific CD8+ T cell immune responses in vaccinated mice. In this study, we tested DNA vaccines encoding the ER chaperone molecules ER-60, tapasin (Tap), or calnexin (Cal), linked to human papillomavirus type 16 (HPV-16) E7 for their abilities to generate E7-specific T cell-mediated immune responses and antitumor effects in vaccinated mice. Our results demonstrated that vaccination with DNA encoding any of these chaperone molecules linked to E7 led to a significant increase in the frequency of E7-specific CD8+ T cell precursors and generated stronger antitumor effects against an E7-expressing tumor in vaccinated mice compared to vaccination with wild-type E7 DNA. Our data suggest that DNA vaccines employing these ER chaperone molecules linked to antigen may enhance antigen-specific CD8+ T cell immune responses, resulting in a significantly more potent DNA vaccine.

Keywords

calnexin DNA vaccines E7 ER-60 human papillomavirus (HPV) immunotherapy tapasin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Donnelly, J.J., Ulmer, J.B., Shiver, J.W., Liu, M.A. 1997DNA vaccines.Annu. Rev. Immunol.15617648CrossRefPubMedGoogle Scholar
  2. Gurunathan, S., Klinman, D.M., Seder, R.A. 2000DNA vaccines: immunology, application, and optimizationAnnu. Rev. Immunol.18927974CrossRefPubMedGoogle Scholar
  3. Leitner, W.W., Ying, H., Restifo, N.P. 1999DNA RNA-based vaccines: principles, progress and prospectsVaccine18765777CrossRefPubMedGoogle Scholar
  4. Robinson, H.L. 1997Nucleic acid vaccines: an overviewVaccine15785787CrossRefPubMedGoogle Scholar
  5. Pardoll, D.M, Beckerleg, A.M 1995Exposing the immunology of naked DNA vaccines.Immunity3165169CrossRefPubMedGoogle Scholar
  6. Rodriguez, F., An, L.L., Harkins, S., Zhang, J., Yokoyama, M., Widera, G., Fuller, J.T., Kincade, C., Campbell, I.L., Whitton, J.L. 1998DNA immunization with minigenes low frequency of memory cytotoxic T lymphocytes and inefficient antiviral protection are rectified by ubiquitinationJ. Virol.7251745181PubMedGoogle Scholar
  7. Tobery, T.W., Siliciano, R.F. 1997Targeting of HIV-1 antigens for rapid intracellular degradation enhances cytotoxic T lymphocyte (CTL) recognition and the induction of de novo CTL responses in vivo after immunization.J. Exp Med.909–920185Google Scholar
  8. Boyle, J.S., Brady, J.L, Lew, A.M. 1998Enhanced responses to a DNA vaccine encoding a fusion antigen that is directed to sites of immune induction.Nature408–411392Google Scholar
  9. Cheng, W.F., Hung, C.F., Chai, C.Y., Hsu, K.F., He, L., Ling, M., Wu, T.C. 2001Tumor-specific immunity and antiangiogenesis generated by a DNA vaccine encoding calreticulin linked to a tumor antigen. J. Clin Invest.669–678108Google Scholar
  10. Hung, C.-F., Hsu, K.-F., Cheng, W.-F., Chai, C.-Y., He, L., Ling, M., Wu, T.-C. 2001Enhancement of DNA vaccine potency by linkage of antigen gene to a gene encoding the extracellular domain of Flt3-ligandCancer Res.1080–108861Google Scholar
  11. Biragyn, A., Tani, K., Grimm, M.C., Weeks, S., Kwak, L.W. 1999Genetic fusion of chemokines to a self tumor antigen induces protective, T-cell dependent antitumor immunity [see comments]Nat. Biotechnol.253–25817Google Scholar
  12. Hung, C.-F., Cheng, W.-F., Hsu, K.-F., Chai, C.-Y., He, L., Ling, M., Wu, T.-C. 2001Cancer immunotherapy using a DNA vaccine encoding the translocation domain of a bacterial toxin linked to a tumor antigenCancer Res.3698–370361Google Scholar
  13. King, CA, Spellerberg, MB, Zhu, D, Rice, J, Sahota, SS, Thompsett, AR, Hamblin, TJ, Radl, J., Stevenson, FK 1998DNA vaccines with single-chain Fv fused to fragment C of tetanus toxin induce protective immunity against lymphoma and myeloma [see comments]Nat. Med.412811286CrossRefPubMedGoogle Scholar
  14. Chow, YH, Chiang, BL, Lee, YL, Chi, WK, Lin, WC, Chen, YT, Tao, MH 1998Development of Th1 and Th2 populations and the nature of immune responses to hepatitis B virus DNA vaccines can be modulated by codelivery of various cytokine genesJ. Immunol.16013201329PubMedGoogle Scholar
  15. Weiss, WR, Ishii, KJ, Hedstrom, RC, Sedegah, M, Ichino, M, Barnhart, K, Klinman, DM, Hoffman, SL 1998A plasmid encoding murine granulocyte-macrophage colony-stimulating factor increases protection conferred by a malaria DNA vaccineJ. Immunol.16123252332PubMedGoogle Scholar
  16. Corr, M, Tighe, H, Lee, D, Dudler, J, Trieu, M, Brinson, DC, Carson, DA 1997Costimulation provided by DNA immunization enhances antitumor immunityJ. Immunol.15949995004PubMedGoogle Scholar
  17. Klinman, DM, Yamshchikov, G, Ishigatsubo, Y 1997Contribution of CpG motifs to the immunogenicity of DNA vaccinesJ. Immunol.15836353639PubMedGoogle Scholar
  18. Condon, C, Watkins, SC, Celluzzi, CM, Thompson, K, Falo, LD 1996DNA-based immunization by in vivo transfection of dendritic cellsNat. Med.211221128CrossRefPubMedGoogle Scholar
  19. Porgador, A, Irvine, KR, Iwasaki, A, Barber, B.H., Restifo, N.P., Germain, R.N. 1998Predominant role for directly transfected dendritic cells in antigen presentation to CD8+ T cells after gene gun immunizationJ. Exp. Med.18810751082CrossRefPubMedGoogle Scholar
  20. Hung, C.F., Wu, T.C. 2003Improving DNA vaccine potency via modification of professional antigen presenting cellsCurr. Opin. Mol. Ther.52024PubMedGoogle Scholar
  21. Lehner, P.J., Trowsdale, J. 1998Antigen presentation: coming out gracefully. Curr. Biol.R605–R6088Google Scholar
  22. Wang, Y., Chen, D., Androlewicz, M.J. 1999The role of endoplasmic reticulum-associated protein degradation in MHC class I antigen processingImmunol. Rev.1726772PubMedGoogle Scholar
  23. Lehner, P.J., Surman, M.J., Cresswell, P. 1998Soluble tapasin restores MHC Class 1 expression and function in the tapasin-negative cell line220. Immunity8221231Google Scholar
  24. Li, S., Paulsson, K.M., Sjögrn, H.-O., Wang, P. 1999Peptide-bound major histocompatibility complex class I molecules associate with tapasin before dissociation from transporter associated with antigen processingJ. Biol. Chem.27486498654PubMedGoogle Scholar
  25. Ortmann, B., Copeman, J., Lehner, P., Sadasivan, B., Herberg, J., Grandea, A.G., Riddell, S.R., Tampe, R., Spies, T., Trowsdale, J. 1997A critical role for tapasin in the assembly and function of multimeric MHC Class 1–TAP complexesScience27713061309PubMedGoogle Scholar
  26. Peh, C.A., Laham, N., Burrows, S.R., Zhu, Y., McCluskey, J. 2000Distinct functions of tapasin revealed by polymorphism in MHC class I peptide loadingJ. Immunol.64292299Google Scholar
  27. Spee, P., Subjeck, J., Neefjes, J. 1999Identification of novel peptide binding proteins in the endoplasmic reticulum: ERp72, calnexin, and grp170Biochemistry381055910566PubMedGoogle Scholar
  28. Williams, D.B. 1995Calnexin: a molecular chaperone with a taste for carbohydrateBiochem. Cell Biol.73123132PubMedGoogle Scholar
  29. Lindquist, J.A., Jensen, O.N., Mann, M., Hämmerling, G. 1998ER-60, a chaperone with thiol-dependent reductase activity involved in MHC class 1 assemblyEMBO J.1721862195PubMedGoogle Scholar
  30. Hughes, E.A., Cresswell, P. 1998The thiol oxidoreductase ERp57 is a component of the MHC class 1 peptide-loading complexCurr. Biol.8709712PubMedGoogle Scholar
  31. Oliver, J.D., Roderick, H.L., Llewellyn, D.H., High, S. 1999ERp57 functions as a subunit of specific complexes formed with the ER lectins calreticulin and calnexinMol. Biol. Cell1025732582PubMedGoogle Scholar
  32. Ellenson, L.H., Wu, T.C. 2004Focus on endometrial and cervical cancerCancer Cell5533538PubMedGoogle Scholar
  33. Chen, C.-H., Wang, T.-L., Hung, C.-F., Yang, Y., Young, R.A., Pardoll, D.M., Wu, T.-C. 2000Enhancement of DNA vaccine potency by linkage of antigen gene to an HSP70 geneCancer Res.6010351042PubMedGoogle Scholar
  34. Lin, K.-Y., Guarnieri, F.G., Staveley-O’Carroll, K.F., Levitsky, H.I., August, T., Pardoll, D.M., Wu, T.-C. 1996Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigenCancer Res.562126PubMedGoogle Scholar
  35. Feltkamp , M.C., Smits, H.L., Vierboom, M.P., Minnaar, R.P., de Jough, B.M., Drijfhout, J.W., ter Schegget, J., Melief, C.J., Kast, W.M. 1993Vaccination with cytotoxic T lymphocyte epitope-containing peptide protects against a tumor induced by human papillomavirus type 16-transformed cellsEur. J. Immunol.2322422249PubMedGoogle Scholar
  36. Tindle, R.W., Fernando, G.J., Sterling, J.C., Frazer, I.H. 1991A ‘public’ T-helper epitope of the E7 transforming protein of human papillomavirus 16 provides cognate help for several E7 B-cell epitopes from cervical cancer-associated human papillomavirus genotypesProc. Natl. Acad. Sci. USA8858875891PubMedGoogle Scholar
  37. Melief, C.J., Kast, W.M. 1995T-cell immunotherapy of tumors by adoptive transfer of cytotoxic T lymphocytes and by vaccination with minimal essential epitopesImmunol. Rev.145167177PubMedGoogle Scholar
  38. Restifo, N.P., Bacik, I., Irvine, K.R., Yewdell, J.W., McCabe, B.J., Anderson, R.W., Eisenlohr, L.C., Rosenberg, S.A., Bennink, J.R. 1995Antigen processing in vivo and the elicitation of primary CTL responsesJ. Immunol.15444144422PubMedGoogle Scholar
  39. Ji, H., Wang, T.-L., Chen, C.-H., Hung, C.-F., Pai, S., Lin, K.-Y., Kurman, R.J., Pardoll, D.M., Wu, T.-C. 1999Targeting HPV-16 E7 to the endosomal/lysosomal compartment enhances the antitumor immunity of DNA vaccines against murine HPV-16 E7-expressing tumorsHuman Gene Ther.1027272740Google Scholar
  40. Nichols, W.W., Ledwith, B.J., Manam, S.V., Troilo, P.J. 1995Potential DNA vaccine integration into host cell genomeAnn. NY Acad. Sci.7723039PubMedGoogle Scholar
  41. Heck, D.V., Yee, C.L., Howley, P.M., Munger, K. 1992Efficiency of binding the retinoblastoma protein correlates with the transforming capacity of the E7 oncoproteins of the human papillomavirusesProc. Natl. Acad. Sci. USA8944424446PubMedGoogle Scholar

Copyright information

© National Science Council, Tapei 2005

Authors and Affiliations

  • Cheng-Tao Lin
    • 1
  • Ting-Chang Chang
    • 1
  • Angel Chao
    • 1
  • Elizabeth Dzeng
    • 2
  • Yung-Kuei Soong
    • 1
  • Chien-Fu Hung
    • 2
  • Chyong-Huey Lai
    • 2
  1. 1.Department of Obstetrics and GynecologyChang Gung Memorial Hospital and Chang Gung UniversityChang Gung Memorial Hospital and Chang Gung UniversityTaoyuanTaiwan
  2. 2.Department of PathologyThe Johns Hopkins University School of MedicineBaltimoreUSA

Personalised recommendations