Alphavirus Hybrid Virion Vaccines
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.
KeywordsSemliki Forest Virus Protective Epitope Foreign Epitope Cross Protective Immunity Cellular Mediate Immunity
Unable to display preview. Download preview PDF.
- 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
- 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
- 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
- 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.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
- 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