A fusion product of the complete Borrelia burgdorferi outer surface protein A (OspA) and the hepatitis B virus capsid protein is highly immunogenic and induces protective immunity similar to that seen with an effective lipidated OspA vaccine formula

European Journal of Immunology

Volumn 35, Issue 2, 2005, Pages 655-665

  Nassal, Michael ^a   Skamel, Claudia ^a   Kratz, Peter A ^a   Wallich, Reinhard ^b   Stehle, Thomas ^c   Simon, Markus M ^c  

^a UNIVERSITY OF FREIBURG   (Germany)

^b UNIVERSITY OF HEIDELBERG   (Germany)

^c MAX PLANCK INSTITUTE OF IMMUNOBIOLOGY AND EPIGENETICS   (Germany)

Author keywords

Adjuvant; Capsid like particles; HBcAg; Lyme borreliosis; OspA vaccine

Indexed keywords

AMINO ACID; BACTERIAL ANTIGEN; BACTERIAL VACCINE; BACTERIUM ANTIBODY; CAPSID PROTEIN; EPITOPE; HYBRID PROTEIN; IMMUNOGLOBULIN G ANTIBODY; IMMUNOGLOBULIN G1 ANTIBODY; IMMUNOGLOBULIN G2A ANTIBODY; IMMUNOGLOBULIN G2B; IMMUNOGLOBULIN G3; MONOCLONAL ANTIBODY; OUTER SURFACE PROTEIN A; PHOSPHORYL LIPID A; POLYPEPTIDE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; B LYMPHOCYTE; BORRELIA BURGDORFERI; CONTROLLED STUDY; DATA ANALYSIS; DRUG EFFICACY; DRUG POTENCY; FEMALE; HEPATITIS B VIRUS; IMMUNITY; IMMUNOGENICITY; LYME DISEASE; NONHUMAN; PRIORITY JOURNAL; PROTECTION; PROTEIN DOMAIN; PROVOCATION TEST; VIRAL GENE DELIVERY SYSTEM;

ANIMALS; ANTIGENS, SURFACE; BACTERIAL OUTER MEMBRANE PROTEINS; BACTERIAL VACCINES; BORRELIA BURGDORFERI; CAPSID PROTEINS; FEMALE; HEPATITIS B ANTIGENS; HEPATITIS B VIRUS; LIPID METABOLISM; LIPOPROTEINS; LYME DISEASE; LYME DISEASE VACCINES; MICE; MICE, INBRED BALB C; MICE, SCID; PROTEIN STRUCTURE, TERTIARY; RECOMBINANT FUSION PROTEINS;

EID: 14744292190     PISSN: 00142980     EISSN: None     Source Type: Journal    
DOI: 10.1002/eji.200425449     Document Type: Article

References (49)

1. Schaible, U. E., Kramer, M. D., Eichmann, K., Modolell, M., Museteanu, C. and Simon, M. M., Monoclonal antibodies specific for the outer surface protein A (OspA) of Borrelia burgdorferi prevent Lyme borreliosis in severe combined immunodeficiency (scid) mice. Proc. Natl. Acad. Sci. USA 1990. 87: 3768-3772.
2. Fikrig, E., Barthold, S. W., Kantor, F. S. and Flavell, R. A., Protection of mice against the Lyme disease agent by immunizing with recombinant OspA. Science 1990. 250: 553-556.
3. Simon, M. M., Schaible, U. E., Kramer, M. D., Eckerskorn, C., Museteanu, C., Muller-Hermelink, H. K. and Wallich, R., Recombinant outer surface protein a from Borrelia burgdorferi induces antibodies protective against spirochetal infection in mice. J. Infect. Dis. 1991. 164: 123-132.
4. Van Hoecke, C., Comberbach, M., De Grave, D., Desmons, P., Fu, D., Hauser, P., Lebacq, E., Lobet, Y. and Voet, P., Evaluation of the safety, reactogenicity and immunogenicity of three recombinant outer surface protein (OspA) lyme vaccines in healthy adults. Vaccine 1996. 14: 1620-1626.
5. Johnson, B. J., Sviat, S. L., Happ, C. M., Dunn, J. J., Frantz, J. C., Mayer, L. W. and Piesman, J., Incomplete protection of hamsters vaccinated with unlipidated OspA from Borrelia burgdorferi infection is associated with low levels of antibody to an epitope defined by mAb LA-2. Vaccine 1995. 13: 1086-1094.
6. Takeda, K., Kaisho, T. and Akira, S., Toll-like receptors. Annu. Rev. Immunol. 2003. 21: 335-376.
7. Sigal, L. H., Zahradnik, J. M., Lavin, P., Patella, S. J., Bryant, G., Haselby, R., Hilton, E., Kunkel, M., Adler-Klein, D., Doherty, T. et al., A vaccine consisting of recombinant Borrelia burgdorferi outer-surface protein A to prevent Lyme disease. Recombinant Outer-Surface Protein A Lyme Disease Vaccine Study Consortium. N. Engl. J. Med. 1998. 339: 216-222.
8. Steere, A. C., Sikand, V. K., Meurice, F., Parenti, D. L., Fikrig, E., Schoen, R. T., Nowakowski, J., Schmid, C. H., Laukamp, S., Buscarino, C. and Krause, D. S., Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. Lyme Disease Vaccine Study Group. N. Engl. J. Med. 1998. 339: 209-215.
9. Noad, R. and Roy, P., Virus-like particles as immunogens. Trends Microbiol. 2003. 11: 438-444.
10. Nassal, M., Hepatitis B virus replication: novel roles for virus-host interactions. Intervirology 1999. 42: 100-116.
11. Nassal, M., Macromolecular interactions in hepatitis B virus replication and particle assembly. In Cann, A. J. (Ed.) DNA virus replication. Oxford University Press, Oxford, UK 2000, pp 1-40.
12. Crowther, R. A., Kiselev, N. A., Böttcher, B., Berriman, J. A., Borisova, G. P., Ose, V. and Pumpens, P., Three-dimensional structure of hepatitis B virus core particles determined by electron cryomicroscopy. Cell 1994. 77: 943-950.
13. Kenney, J. M., von Bonsdorff, C. H., Nassal, M. and Fuller, S. D., Evolutionary conservation in the hepatitis B virus core structure: comparison of human and duck cores. Structure 1995. 3: 1009-1019.
14. Birnbaum, F. and Nassal, M., Hepatitis B virus nucleocapsid assembly: primary structure requirements in the core protein. J. Virol. 1990. 64: 3319-3330.
15. Watts, N. R., Conway, J. F., Cheng, N., Stahl, S. J., Belnap, D. M., Steven, A. C. and Wingfield, P. T., The morphogenic linker peptide of HBV capsid protein forms a mobile array on the interior surface. EMBO J. 2002. 21: 876-884.
16. Nassal, M., The arginine-rich domain of the hepatitis B virus core protein is required for pregenome encapsidation and productive viral positive-strand DNA synthesis but not for virus assembly. J. Virol. 1992. 66: 4107-4116.
17. Wynne, S. A., Crowther, R. A. and Leslie, A. G., The crystal structure of the human hepatitis B virus capsid. Mol. Cell 1999. 3: 771-780.
18. Böttcher, B., Wynne, S. A. and Crowther, R. A., Determination of the fold of the core protein of hepatitis B virus by electron cryomicroscopy. Nature 1997. 386: 88-91.
19. Conway, J. F., Cheng, N., Zlotnick, A., Stahl, S. J., Wingfield, P. T., Belnap, D. M., Kanngiesser, U., Noah, M. and Steven, A. C., Hepatitis B virus capsid: localization of the putative immunodominant loop (residues 78 to 83) on the capsid surface, and implications for the distinction between c and e-antigens. J. Mol. Biol. 1998. 279: 1111-1121.
20. Belnap, D. M., Watts, N. R., Conway, J. F., Cheng, N., Stahl, S. J., Wingfield, P. T. and Steven, A. C., Diversity of core antigen epitopes of hepatitis B virus. Proc. Natl. Acad. Sci. USA 2003. 100: 10884-10889.
21. Chisari, F. V. and Ferrari, C., Hepatitis B virus immunopathogenesis. Annu. Rev. Immunol. 1995. 13: 29-60.
22. Salfeld, J., Pfaff, E., Noah, M. and Schaller, H., Antigenic determinants and functional domains in core antigen and e antigen from hepatitis B virus. J. Virol. 1989. 63: 798-808.
23. Fehr, T., Skrastina, D., Pumpens, P. and Zinkernagel, R. M., T cell-independent type I antibody response against B cell epitopes expressed repetitively on recombinant virus particles. Proc. Natl. Acad. Sci. USA 1998. 95: 9477-9481.
24. Milich, D. R. and McLachlan, A., The nucleocapsid of hepatitis B virus is both a T cell-independent and a T cell-dependent antigen. Science 1986. 234: 1398-1401.
25. Milich, D. R., Chen, M., Schödel, F., Peterson, D. L., Jones, J. E. and Hughes, J. L., Role of B cells in antigen presentation of the hepatitis B core. Proc. Natl. Acad. Sci. USA 1997. 94: 14648-14653.
26. Lazdina, U., Cao, T., Steinbergs, J., Alheim, M., Pumpens, P., Peterson, D. L., Milich, D. R., Leroux-Roels, G. and Sällberg, M., Molecular basis for the interaction of the hepatitis B virus core antigen with the surface immunoglobulin receptor on naive B cells. J. Virol. 2001. 75: 6367-6374.
27. Pumpens, P. and Grens, E., HBV core particles as a carrier for B cell/T cell epitopes. Intervirology 2001. 44: 98-114.
28. Cao, T., Lazdina, U., Desombere, I., Vanlandschoot, P., Milich, D. R., Sällberg, M. and Leroux-Roels, G., Hepatitis B virus core antigen binds and activates naive human B cells in vivo: studies with a human PBL-NOD/SCID mouse model. J. Virol. 2001. 75: 6359-6366.
29. Lazdina, U., Alheim, M., Nystrom, J., Hultgren, C., Borisova, G., Sominskaya, I., Pumpens, P., Peterson, D. L., Milich, D. R. and Sällberg, M., Priming of cytotoxic T cell responses to exogenous hepatitis B virus core antigen is B cell dependent. J. Gen. Virol. 2003. 84: 139-146.
30. Ulrich, R., Nassal, M., Meisel, H. and Krüger, D. H., Core particles of hepatitis B virus as carrier for foreign epitopes. Adv. Virus Res. 1998. 50: 141-182.
31. Birkett, A., Lyons, K., Schmidt, A., Boyd, D., Oliveira, G. A., Siddique, A., Nussenzweig, R., Calvo-Calle, J. M. and Nardin, E., A modified hepatitis B virus core particle containing multiple epitopes of the Plasmodium falciparum circumsporozoite protein provides a highly immunogenic malaria vaccine in preclinical analyses in rodent and primate hosts. Infect. Immun. 2002. 70: 6860-6870.
32. Sällberg, M., Hughes, J., Jones, J., Phillips, T. R. and Milich, D. R., A malaria vaccine candidate based on a hepatitis B virus core platform. Intervirology 2002. 45: 350-361.
33. Kazaks, A., Lachmann, S., Koletzki, D., Petrovskis, I., Dislers, A., Ose, V., Skrastina, D., Gelderblom, H. R., Lundkvist, A., Meisel, H. et al., Stop codon insertion restores the particle formation ability of hepatitis B virus core-hantavirus nucleocapsid protein fusions. Intervirology 2002. 45: 340-349.
34. Kratz, P. A., Böttcher, B. and Nassal, M., Native display of complete foreign protein domains on the surface of hepatitis B virus capsids. Proc. Natl. Acad. Sci. USA 1999. 96: 1915-1920.
35. Vogel, M., Vorreiter, J. and Nassal, M., Quaternary structure is critical for protein display on capsid-like particles (CLPs): Efficient generation of hepatitis B virus CLPs presenting monomeric but not dimeric and tetrameric fluorescent proteins. Proteins 2004. DOI: 10.1002/prot.20312
36. Geldmacher, A., Skrastina, D., Petrovskis, I., Borisova, G., Berriman, J. A., Roseman, A. M., Crowther, R. A., Fischer, J., Musema, S., Gelderblom, H. R. et al., An amino-terminal segment of hantavirus nucleocapsid protein presented on hepatitis B virus core particles induces a strong and highly cross-reactive antibody response in mice. Virology 2004. 323: 108-119.
37. Wallich, R., Schaible, U. E., Simon, M. M., Heiberger, A. and Kramer, M. D., Cloning and sequencing of the gene encoding the outer surface protein A (OspA) of a European Borrelia burgdorferi isolate. Nucleic Acids Res. 1989. 17: 8864.
38. Schaible, U. E., Gern, L., Wallich, R., Kramer, M. D., Prester, M. and Simon, M. M., Distinct patterns of protective antibodies are generated against Borrelia burgdorferi in mice experimentally inoculated with high and low doses of antigen. Immunol. Lett. 1993. 36: 219-226.
39. Zhong, W., Gern, L., Stehle, T., Museteanu, C., Kramer, M., Wallich, R. and Simon, M. M., Resolution of experimental and tick-borne Borrelia burgdorferi infection in mice by passive, but not active immunization using recombinant OspC. Eur. J. Immunol. 1999. 29: 946-957.
40. Wallich, R., Jahraus, O., Stehle, T., Tran, T. T., Brenner, C., Hofmann, H., Gern, L. and Simon, M. M., Artificial-infection protocols allow immunodetection of novel Borrelia burgdorferi antigens suitable as vaccine candidates against Lyme disease. Eur. J. Immunol. 2003. 33: 708-719.
41. Ormo, M., Cubitt, A. B., Kallio, K., Gross, L. A., Tsien, R. Y. and Remington, S. J., Crystal structure of the Aequorea victoria green fluorescent protein. Science 1996. 273: 1392-1395.
42. Li, H., Dunn, J. J., Luft, B. J. and Lawson, C. L., Crystal structure of Lyme disease antigen outer surface protein A complexed with an Fab. Proc. Natl. Acad. Sci. USA 1997. 94: 3584-3589.
43. Ding, W., Huang, X., Yang, X., Dunn, J. J., Luft, B. J., Koide, S. and Lawson, C. L., Structural identification of a key protective B cell epitope in Lyme disease antigen OspA. J. Mol. Biol. 2000. 302: 1153-1164.
44. Zlotnick, A. and Stray, S. J., How does your virus grow? Understanding and interfering with virus assembly. Trends Biotechnol. 2003. 21: 536-542.
45. Kramer, M. D., Schaible, U. E., Wallich, R., Moter, S. E., Petzoldt, D. and Simon, M. M., Characterization of Borrelia burgdorferi associated antigens by monoclonal antibodies. Immunobiology 1990. 181: 357-366.
46. Sällberg, M., Pushko, P., Berzinsh, I., Bichko, V., Sillekens, P., Noah, M., Pumpens, P., Grens, E., Wahren, B. and Magnius, L. O., Immunochemical structure of the carboxy-terminal part of hepatitis B e antigen: identification of internal and surface-exposed sequences. J. Gen. Virol. 1993. 74: 1335-1340.
47. Schaible, U. E., Wallich, R., Kramer, M. D., Museteanu, C. and Simon, M. M., A mouse model for Borrelia burgdorferi infection: pathogenesis, immune response and protection. Behring Inst. Mitt. 1991: 59-67.
48. Simon, M. M., Gern, L., Hauser, P., Zhong, W., Nielsen, P. J., Kramer, M. D., Brenner, C. and Wallich, R., Protective immunization with plasmid DNA containing the outer surface lipoprotein A gene of Borrelia burgdorferi is independent of an eukaryotic promoter. Eur. J. Immunol. 1996. 26: 2831-2840.
49. Zhong, W., Stehle, T., Museteanu, C., Siebers, A., Gern, L., Kramer, M., Wallich, R. and Simon, M. M., Therapeutic passive vaccination against chronic Lyme disease in mice. Proc. Natl. Acad. Sci. USA 1997. 94: 12533-12538.