Alphavirus Hybrid Virion Vaccines

  • A. Shafferman
  • S. Lustig
  • Y. Inbar
  • M. Halevy
  • P. Schneider
  • T. Bino
  • M. Leitner
  • H. Grosfeld
  • B. Velan
  • F. Schödel
  • S. Cohen
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 397)

Abstract

Many members of the alphavirus family are important human or veterinary pathogens. These viruses are extremely similar in molecular architecture yet differ in host range and in the pathological consequences of infection. Despite marked structural conservation, the various species are inefficient in eliciting immunological cross protection. Previously(l) we described a systematic approach for selection of epitope-cassettes of the E2 envelope of the alphavirus family that induce virus species specific protective immunity. This approach was tested and proved successful(2–5) with two viruses - Sindbis (SIN) and Semliki Forest (SF) - which are very remote phylogenetically. Vaccination was performed with recombinant peptide cassettes fused to a bacterial protein carrier (β-galactosidase) formulated with different adjuvants. In order to create a vaccine compatible with human use, we designed several live vector vaccines for presentation of the protective epitope cassette. Attenuated salmonella vaccine vector which can potentially allow presentation of many different cassettes and thus generation of a pan-alphavirus vaccine, proved to be inefficient. On the other hand the live attenuated viral vaccine based on a benign alphavirus such as SIN vector, appears to be promising. The principle of such vaccines is substitution of E2 epitopes of SIN virus vector with parallel protective epitopes from a different alphavirus. This system should have the advantage of presentation of specific virus epitopes in the context of the SIN alphavirus backbone which in turn could provide cross protective immunity on the basis of multiple common antigen determinants.

Keywords

Placebo Hepatitis Polyacrylamide Malaria Kelly 

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References

  1. 1.
    Grosfeld, H., Velan, B., Olshevsky, U., Leitner, M., Lachmi, B.-E., Pinto, M. and Shafferman, A. 1988. An approach towards development of synthetic prototype model vaccine for alphaviruses. UCLA Symp. Mol. Cell. Biol. New Ser. 84: 87–96.Google Scholar
  2. 2.
    Grosfeld, H., Velan, B., Leitner, M., Cohen, S., Lustig, S., Lachmi, B.-E. and Shafferman, A. 1989. Semliki Forest Virus E2 envelope epitopes induce a nonneutralizing humoral response which protects mice against lethal challenge. J.Virol. 63: 3416–3422.PubMedGoogle Scholar
  3. 3.
    Shafferman, A., Grosfeld, H., Leitner, M., Cohen, S., Olshevsky, U., Lachmi, B.-E., Lustig, S. and Velan, B. 1990. Selection and analysis of protective epitopes on the E2 envelope of Semliki Forest Virus. In: Vaccines 90. (Eds. Brown, F., Chanock R.M., Ginsberg, H.S. and Lerner, R.A.) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. p.p. 115–118Google Scholar
  4. 4.
    Grosfeld, H., Velan, B., Leitner, M., Lustig, S., Lachmi, B.-E., Cohen, S. and Shafferman, A. 1991. The delineation of protective epitopes on the E2-envelope glycoprotein of Semliki Forest virus. Vaccine 9: 451–456.PubMedCrossRefGoogle Scholar
  5. 5.
    Grosfeld, H., Lustig, S., Gozes, Y., Velan, B., Cohen, S., Leitner, M., Lachmi, B.-E., Katz, D., Olshevsky, U. and Shafferman, A. 1992. Divergent envelope E2 Alphavirus sequences spanning amino acids 297 to 352 induce in mice virus-specific protective immunity and antibodies with complement-mediated cy-tolytic activity. J. Virol. 66:1084–1090.PubMedGoogle Scholar
  6. 6.
    Hoiseth, S.K. and Stocker, B.A.D. 1981. Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines. Nature, 291: 238–239.PubMedCrossRefGoogle Scholar
  7. 7.
    Curtiss, R. III and Kelly, S.M. 1987. Salmonella typhimurium deletion mutants lacking adenylate cyclase and cyclic AMP receptor protein are avirulent and immunogenic. Infect. Immun., 55: 3035–3043PubMedGoogle Scholar
  8. 8.
    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. Biotechnology, 6: 693–797.CrossRefGoogle Scholar
  9. 9.
    Tsai, C-M. and Frasch, C.E. 1982. A sensitive silver stain for detecting lipopolysaccharides in polyacry-lamide gels. Anal. Biochem., 119: 115–119.PubMedCrossRefGoogle Scholar
  10. 10.
    Hitchcock, PJ. and Brown, T.M. 1983. Morphological heterogeneity among Salmonella lipopolysaccharide chemotypes in silver-stained polyacrylamide gels. J. Bacteriol., 154: 269–277.PubMedGoogle Scholar
  11. 11.
    Schödel, F., Milich, D.R. and Will, H. 1991. Hybrid hepatitis B virus core/pre-S particles expressed in attenuated Salmonella for oral immunization. In: Vaccines 91 (Eds. Brown, F., Chanock, R.M., Ginsberg, H.S and Lerner, R.A.) Cold Spring Harbor’ laboratory, Cold Spring Harbor, N.Y. p.p. 319–325.Google Scholar
  12. 12.
    Rice, C.M., Levis, R., Strauss, J.H. and Huang, H.V. 1987. Production of infectious RNA transcripts from Sindbis virus cDNA clones: mapping of lethal mutation, rescue of a temperature-sensitive marker, and in vitro mutagenesis to generate defined mutants. J. Virol. 3809-3819.Google Scholar
  13. 13.
    London, S.D., Schmaljohn, A.L., Dalrymple, J.M. and Rice, C.M. 1991. Infectious enveloped RNA virus antigenic chimeras. Proc. Natl. Acad. Sci. USA 89: 207–211.CrossRefGoogle Scholar
  14. 14.
    Cohen, S., Powell, C.J., Dubois, D.R., Hartman, A., Summers, P.L. and Eckels, K.H. 1990. Expression of the envelope antigen of dengue virus in vaccine strains of Salmonella, Res. Microbiol. 141: 855–858.PubMedCrossRefGoogle Scholar
  15. 15.
    Sadoff, J.C, Ballou, W.R., Baron, L.S., Majarian, W.R., Brey, R.N., Hockmeyer, W.T., Young, J.F., Cryz, S.J., Ou, J., Lowell, G.H. and Chulay, J.D. 1988. Salmonella typhimurium vaccine expressing circumsporozoite protein protects against malaria. Science (Wash. DC), 240: 336.CrossRefGoogle Scholar
  16. 16.
    Aggarwal, A., Kumar, S., Jaffe, R., Hone, D., Gross, M. and Sadoff, J. 1990. Oral Salmonella: Malaria circumsporozoite recombinants induce specific CD8+ cytotoxic T cells. J. Exp. Med. 172: 1083–1090.PubMedCrossRefGoogle Scholar
  17. 17.
    Schödel, F., Kelly, S., Tinge, S., Hopkins, S., Peterson, D., Milich, D. and Curtiss, R. III. 1996. Hybrid Hepatitis B virus core antigen as a vaccine carrier moiety. In “Novel Strategies in Design and Production of Vaccines.” (Eds. Cohen, S and. Shafferman, A.) Plenum Press. this volume.Google Scholar
  18. 18.
    Ariel, N., Lehrer, S., Elhanaty, E., Sabo, T., Brodt, P., Lachmi, B., Katz, D., Levin, R., Grosfeld, H., Velan, B. and Shafferman, A. 1990. Serologically defined linear epitopes in the E2 envelope glycoprotein of Semliki Forest virus. Arch. Virol. 113: 99–106.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • A. Shafferman
    • 1
  • S. Lustig
    • 2
  • Y. Inbar
    • 1
  • M. Halevy
    • 2
  • P. Schneider
    • 2
  • T. Bino
    • 1
  • M. Leitner
    • 1
  • H. Grosfeld
    • 1
  • B. Velan
    • 1
  • F. Schödel
    • 3
  • S. Cohen
    • 1
  1. 1.Department of Biochemistry and Molecular GeneticsIsrael Institute for Biological ResearchNess-ZionaIsrael
  2. 2.Department of Infectious DiseasesIsrael Institute for Biological ResearchNess-ZionaIsrael
  3. 3.INSERM U 80, Pavillon PHôpital Edouard HerriotLyon Cedex 03France

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