Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Feb 1;88(3):991–993. doi: 10.1073/pnas.88.3.991

Peptide-induced antiviral protection by cytotoxic T cells.

M Schulz 1, R M Zinkernagel 1, H Hengartner 1
PMCID: PMC50940  PMID: 1992491

Abstract

A specific antiviral cytotoxic immune response in vivo could be induced by the subcutaneous injection of the T-cell epitope of the lymphocytic choriomeningitis virus (LCMV) nucleoprotein as an unmodified free synthetic peptide (Arg-Pro-Gln-Ala-Ser-Gly-Val-Tyr-Met-Gly-Asn-Leu-Thr-Ala-Gln) emulsified in incomplete Freund's adjuvant. This immunization rendered mice into a LCMV-specific protective state as shown by the inhibition of LCMV replication in spleens of such mice. The protection level of these mice correlated with the ability to respond to the peptide challenge by CD8+ virus-specific cytotoxic T cells. This is a direct demonstration that peptide vaccines can be antivirally protective in vivo, thus encouraging further search for appropriate mixtures of stable peptides that may be used as T-cell vaccines.

Full text

PDF
991

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aichele P., Hengartner H., Zinkernagel R. M., Schulz M. Antiviral cytotoxic T cell response induced by in vivo priming with a free synthetic peptide. J Exp Med. 1990 May 1;171(5):1815–1820. doi: 10.1084/jem.171.5.1815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Buchmeier M. J., Welsh R. M., Dutko F. J., Oldstone M. B. The virology and immunobiology of lymphocytic choriomeningitis virus infection. Adv Immunol. 1980;30:275–331. doi: 10.1016/s0065-2776(08)60197-2. [DOI] [PubMed] [Google Scholar]
  3. Carbone F. R., Bevan M. J. Induction of ovalbumin-specific cytotoxic T cells by in vivo peptide immunization. J Exp Med. 1989 Mar 1;169(3):603–612. doi: 10.1084/jem.169.3.603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cobbold S. P., Jayasuriya A., Nash A., Prospero T. D., Waldmann H. Therapy with monoclonal antibodies by elimination of T-cell subsets in vivo. Nature. 1984 Dec 6;312(5994):548–551. doi: 10.1038/312548a0. [DOI] [PubMed] [Google Scholar]
  5. Deres K., Schild H., Wiesmüller K. H., Jung G., Rammensee H. G. In vivo priming of virus-specific cytotoxic T lymphocytes with synthetic lipopeptide vaccine. Nature. 1989 Nov 30;342(6249):561–564. doi: 10.1038/342561a0. [DOI] [PubMed] [Google Scholar]
  6. Hany M., Oehen S., Schulz M., Hengartner H., Mackett M., Bishop D. H., Overton H., Zinkernagel R. M. Anti-viral protection and prevention of lymphocytic choriomeningitis or of the local footpad swelling reaction in mice by immunization with vaccinia-recombinant virus expressing LCMV-WE nucleoprotein or glycoprotein. Eur J Immunol. 1989 Mar;19(3):417–424. doi: 10.1002/eji.1830190302. [DOI] [PubMed] [Google Scholar]
  7. Herberman R. B., Djeu J., Kay H. D., Ortaldo J. R., Riccardi C., Bonnard G. D., Holden H. T., Fagnani R., Santoni A., Puccetti P. Natural killer cells: characteristics and regulation of activity. Immunol Rev. 1979;44:43–70. doi: 10.1111/j.1600-065x.1979.tb00267.x. [DOI] [PubMed] [Google Scholar]
  8. Ishioka G. Y., Colon S., Miles C., Grey H. M., Chesnut R. W. Induction of class I MHC-restricted, peptide-specific cytolytic T lymphocytes by peptide priming in vivo. J Immunol. 1989 Aug 15;143(4):1094–1100. [PubMed] [Google Scholar]
  9. Lehmann-Grube F., Ambrassat J. A new method to detect lymphocytic choriomeningitis virus-specific antibody in human sera. J Gen Virol. 1977 Oct;37(1):85–92. doi: 10.1099/0022-1317-37-1-85. [DOI] [PubMed] [Google Scholar]
  10. Pircher H., Moskophidis D., Rohrer U., Bürki K., Hengartner H., Zinkernagel R. M. Viral escape by selection of cytotoxic T cell-resistant virus variants in vivo. Nature. 1990 Aug 16;346(6285):629–633. doi: 10.1038/346629a0. [DOI] [PubMed] [Google Scholar]
  11. Rothbard J. Synthetic peptides as vaccines. Nature. 1987 Nov 12;330(6144):106–107. doi: 10.1038/330106b0. [DOI] [PubMed] [Google Scholar]
  12. Schulz M., Aichele P., Vollenweider M., Bobe F. W., Cardinaux F., Hengartner H., Zinkernagel R. M. Major histocompatibility complex--dependent T cell epitopes of lymphocytic choriomeningitis virus nucleoprotein and their protective capacity against viral disease. Eur J Immunol. 1989 Sep;19(9):1657–1667. doi: 10.1002/eji.1830190921. [DOI] [PubMed] [Google Scholar]
  13. Staerz U. D., Karasuyama H., Garner A. M. Cytotoxic T lymphocytes against a soluble protein. Nature. 1987 Oct 1;329(6138):449–451. doi: 10.1038/329449a0. [DOI] [PubMed] [Google Scholar]
  14. Takahashi H., Takeshita T., Morein B., Putney S., Germain R. N., Berzofsky J. A. Induction of CD8+ cytotoxic T cells by immunization with purified HIV-1 envelope protein in ISCOMs. Nature. 1990 Apr 26;344(6269):873–875. doi: 10.1038/344873a0. [DOI] [PubMed] [Google Scholar]
  15. Welsh R. M., Jr, Zinkernagel R. M. Heterospecific cytotoxic cell activity induced during the first three days of acute lymphocytic choriomeningitis virus infection in mice. Nature. 1977 Aug 18;268(5621):646–648. doi: 10.1038/268646a0. [DOI] [PubMed] [Google Scholar]
  16. Whitton J. L., Gebhard J. R., Lewicki H., Tishon A., Oldstone M. B. Molecular definition of a major cytotoxic T-lymphocyte epitope in the glycoprotein of lymphocytic choriomeningitis virus. J Virol. 1988 Mar;62(3):687–695. doi: 10.1128/jvi.62.3.687-695.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES