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Hybrid Hepatitis B Virus Core Antigen as a Vaccine Carrier Moiety

II. Expression in Avirulent Salmonella spp. for Mucosal Immunization
  • F. Schödel
  • S. Kelly
  • S. Tinge
  • S. Hopkins
  • D. Peterson
  • D. Milich
  • R. CurtissIII
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 397)

Abstract

Hepatitis B virus (HBV) core antigen (HBcAg) is a highly immunogenic subviral particle. We and others have defined insertion sites for heterologous epitopes and successfully used hybrid particles to generate B and T cell immunity (reviewed in: Schödel et al. 1994a, 1995). Here we shall review recent progress in constructing avirulent Salmonella spp. expressing hybrid HBcAg particles carrying different epitopes. Hybrid HBcAg particles carrying virus neutralizing epitopes of the hepatitis B virus pre-S region or repeat epitopes of plasmodial circumsporozoite antigens were previously described (Schödel et al. 1992, 1994b). Salmonella spp. can be attenuated by defined genetic means so that they become avirulent, yet preserve invasiveness after oral uptake.

Hybrid HBcAg-pre-S particles were expressed in Salmonella typhimurium and S. typhi vaccine strains. A single oral immunization of mice with such live recombinant S. typhimurium strains elicited a high titered serum anti-pre-S1 IgG response. Similarly, circumsporozoite repeat epitopes of three different malaria parasites were expressed as HBcAg-CS hybrids in recombinant S. spp. and were found to be highly immunogenic after oral immunization.

To analyze mucosal immune responses, BALB/c mice were immunized with recombinant phoP c S.typhimurium expressing HBcAg by various mucosal routes (Hopkins et al., 1995). All routes of immunization resulted in high titered serum and local antibodies against HBcAg and S. typhimurium LPS. However, nasal immunization was most efficient in generating pulmonary IgA and rectal immunization in eliciting rectal IgA, suggesting some compartmentalization of the mucosal immune response.

Keywords

Vaccine Strain Mucosal Immune Response Oral Immunization Woodchuck Hepatitis Virus Nasal Immunization 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Cardenas, L., Dasgupta, U. and Clements, J.D. 1994. Influence of strain viability and antigen dose on the use of attenuated mutants of Salmonella as vaccine carriers. Vaccine 12: 833–840PubMedCrossRefGoogle Scholar
  2. Crowther, R. A., Kiselev, N. A., Böttcher, B., Berriman, J. A., Borisova, G. P., Ose, V. and Pumpens, P. 1994. Three-dimensional structure of hepatitis B virus core particles determined by electron microscopy. Cell, 77: 943–950.PubMedCrossRefGoogle Scholar
  3. Curtiss, R III. Attenuated Salmonella strains as live vectors for the expression of foreign antigens, In G. C. Woodrow and M. M. Levine (eds.), New Generation Vaccines. Marcel Dekker, Inc., New York, 1990, pp. 161–188.Google Scholar
  4. Galan J.E., Nakayama K., and Curtiss R. III. 1990. Cloning and characterization of the asd gene of Salmonella typhimurium: use in stable maintenance of recombinant plasmids in Salmonella typhimurium. Gene 94: 29–35.PubMedCrossRefGoogle Scholar
  5. Hopkins, S., Kraehenbuhl, J.P., Schödel, F., Potts, A., Peterson, D., De Grandi, P. and Nardelli, D. 1995. A recombinant Salmonella typhimurium vaccine induces local immunity by four different routes of immunization. Infect. Immun. 63:3279–3286.PubMedGoogle Scholar
  6. Milich, D. R. 1988 T and B cell recognition of hepatitis B viral antigens. Immunol. Today 9:380–386.PubMedCrossRefGoogle Scholar
  7. Nakayama K., Kelly S.M., and Curtiss R. III. 1988. Construction of an Asd+ expression-cloning vector: Stable maintenance and high level expression of cloned genes in a Salmonella vaccine strain. Biotechnol. 6:693–697.CrossRefGoogle Scholar
  8. Schödel, F. 1992. Prospects for oral vaccination using recombinant bacteria expressing viral epitopes. Adv. Virus. Res. 41:409–446.PubMedCrossRefGoogle Scholar
  9. Schödel, F., Milich D.R., Will H. 1990. Hepatitis B virus nucleocapsid/pre-S2 fusion proteins expressed in attenuated Salmonella for oral immunization. J. Immunol. 145: 4317–4321.PubMedGoogle Scholar
  10. Schödel, F., Moriarty, A.M., Peterson, D.L., Zheng, J., Hughes, J.L., Will, H., Leturcq, D.J., McGee, J.S. and Milich, D.R. 1992. The position of heterologous epitopes inserted in hepatitis B virus core particles determines their immunogenicity. J. Virol. 66: 106–114.PubMedGoogle Scholar
  11. Schödel, F., Peterson D., Hughes J.L., Milich D.R. 1993a. Hybrid hepatitis B virus core/pre-S particles: position effects on immunogenicity of heterologous epitopes and expression in avirulent salmonellae for oral vaccination. In: NATO ASI: Series A: Life Sciences Vol. 245: The Biology of Salmonella, F. Cabello, C. Hormaeche, P. Mastroeni, L. Bonina (eds.). Plenum Publishing Corp., New York, NY pp. 347–353.Google Scholar
  12. Schödel, F., Neckermann G., Peterson D., Fuchs K., Fuller S., Will H. and Roggendorf M. 1993b: Immunization with recombinant woodchuck hepatitis virus nucleocapsid antigen or hepatitis B virus nucleocapsid antigen protects woodchucks from woodchuck hepatitis virus infection. Vaccine 11: 624–628.PubMedCrossRefGoogle Scholar
  13. Schödel, F., Peterson, D., Hughes, J. and Milich, D.R. 1994a. Hepatitis B virus core particles as a vaccine carrier moiety. Int. Rev. Immunol. 11: 153–164.PubMedCrossRefGoogle Scholar
  14. Schödel, F., Wirtz, R., Peterson, D., Hughes, J., Warren, R., Sadoff, J. and Milich, D. 1994b. Immunity to malaria elicited by hybrid hepatitis B virus core particles carrying circumsporozoite protein epitopes. J.Exp.Med. 180: 1037–1046.PubMedCrossRefGoogle Scholar
  15. Schödel, F., Kelly S.M., Peterson D., Milich D., Hughes J., Tinge S., Wirtz R., and Curtiss R. 1994c. Development of recombinant Salmonellae expressing hybrid hepatitis B virus core particles as candidate oral vaccines. Dev. Biol. Stand. 82: 151–158.PubMedGoogle Scholar
  16. Schödel, F., Kelly S.M., Peterson D.L., Milich D.R. and Curtiss R. III. 1994d. Hybrid hepatitis B virus core/pre-S proteins synthesized in avirulent Salmonella typhimurium and Salmonella typhi for oral vaccination. Infect. Immun. 62: 1669–1676.PubMedGoogle Scholar
  17. Schödel, F., Peterson D., Hughes J., Wirtz R. and Milich D. 1995. Hybrid hepatitis B virus core antigen as a vaccine carrier moiety. I. Presentation of foreign epitopes. J. Biotech, in press.Google Scholar
  18. von Brunn, A., Brand M., Reichhuber C., Morys-Wortmann C., Deinhardt F., and Schödel F. 1993. The principal neutralizing domain of HIV-1 is highly immunogenic when expressed on the surface of hepatitis B core particles. Vaccine 11:817–824.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • F. Schödel
    • 1
  • S. Kelly
    • 2
  • S. Tinge
    • 2
  • S. Hopkins
    • 3
  • D. Peterson
    • 4
  • D. Milich
    • 5
  • R. CurtissIII
    • 6
  1. 1.INSERM U 80, Pavillon PHôpital Edouard HerriotLyon Cedex 03France
  2. 2.Megan Animal HealthSt. LouisUSA
  3. 3.Department of Biochemistry, ISRECUniversity of LausanneEpalingesSwitzerland
  4. 4.Department of BiochemistryVirginia Commonwealth UniversityRichmondUSA
  5. 5.Department of Molecular BiologyThe Scripps Research InstituteLa JollaUSA
  6. 6.Department of BiologyWashington UniversitySt. LouisUSA

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