Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1991 Mar;72(3):317–322.

Immune-stimulating complexes containing Quil A and protein antigen prime class I MHC-restricted T lymphocytes in vivo and are immunogenic by the oral route.

A M Mowat 1, A M Donachie 1, G Reid 1, O Jarrett 1
PMCID: PMC1384389  PMID: 2026440

Abstract

Induction of all forms of protective immunity by oral immunization with subunit vaccines is an ideal goal for the development of novel vaccines, but creates several theoretical problems from the point of view of antigen processing mechanisms. We show here that incorporation of the protein antigen ovalbumin (OVA) in lipophilic immune-stimulating complexes (ISCOMS) induces very strong primary immune responses in mice and requires very small amounts of antigen. OVA ISCOMS were particularly efficient at stimulating T-cell-mediated immunity in vivo, including delayed-type hypersensitivity (DTH) and potent class I major histocompatibility complex (MHC)-restricted cytotoxic T-cell responses. Furthermore, unlike native protein, OVA in ISCOMS was immunogenic when given orally. Thus, ISCOMS seem to allow protein to enter both the endogenous and exogenous pathways of antigen processing and overcome the usual induction of tolerance after feeding antigen. ISCOMS could provide potentially useful adjuvants for the development of oral subunit vaccines.

Full text

PDF
317

Selected References

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

  1. Bloom B. R. Vaccines for the Third World. Nature. 1989 Nov 9;342(6246):115–120. doi: 10.1038/342115a0. [DOI] [PubMed] [Google Scholar]
  2. Borland A., Mowat A. M., Parrott D. M. Augmentation of intestinal and peripheral natural killer cell activity during the graft-versus-host reaction in mice. Transplantation. 1983 Nov;36(5):513–519. doi: 10.1097/00007890-198311000-00009. [DOI] [PubMed] [Google Scholar]
  3. Carbone F. R., Moore M. W., Sheil J. M., Bevan M. J. Induction of cytotoxic T lymphocytes by primary in vitro stimulation with peptides. J Exp Med. 1988 Jun 1;167(6):1767–1779. doi: 10.1084/jem.167.6.1767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cherwinski H. M., Schumacher J. H., Brown K. D., Mosmann T. R. Two types of mouse helper T cell clone. III. Further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridization, functionally monospecific bioassays, and monoclonal antibodies. J Exp Med. 1987 Nov 1;166(5):1229–1244. doi: 10.1084/jem.166.5.1229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cresswell P. Immunology: questions of presentation. Nature. 1990 Feb 15;343(6259):593–594. doi: 10.1038/343593a0. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Hosken N. A., Bevan M. J., Carbone F. R. Class I-restricted presentation occurs without internalization or processing of exogenous antigenic peptides. J Immunol. 1989 Feb 15;142(4):1079–1083. [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. Jones P. D., Tha Hla R., Morein B., Lovgren K., Ada G. L. Cellular immune responses in the murine lung to local immunization with influenza A virus glycoproteins in micelles and immunostimulatory complexes (iscoms). Scand J Immunol. 1988 Jun;27(6):645–652. doi: 10.1111/j.1365-3083.1988.tb02397.x. [DOI] [PubMed] [Google Scholar]
  10. Long E. O., Jacobson S. Pathways of viral antigen processing and presentation to CTL: defined by the mode of virus entry? Immunol Today. 1989 Feb;10(2):45–48. doi: 10.1016/0167-5699(89)90303-4. [DOI] [PubMed] [Google Scholar]
  11. Lövgren K. The serum antibody response distributed in subclasses and isotypes after intranasal and subcutaneous immunization with influenza virus immunostimulating complexes. Scand J Immunol. 1988 Feb;27(2):241–245. doi: 10.1111/j.1365-3083.1988.tb02343.x. [DOI] [PubMed] [Google Scholar]
  12. Moore M. W., Carbone F. R., Bevan M. J. Introduction of soluble protein into the class I pathway of antigen processing and presentation. Cell. 1988 Sep 9;54(6):777–785. doi: 10.1016/s0092-8674(88)91043-4. [DOI] [PubMed] [Google Scholar]
  13. Morein B. Potentiation of the immune response by immunization with antigens in defined multimeric physical forms. Vet Immunol Immunopathol. 1987 Dec;17(1-4):153–159. doi: 10.1016/0165-2427(87)90136-x. [DOI] [PubMed] [Google Scholar]
  14. Morein B., Sundquist B., Höglund S., Dalsgaard K., Osterhaus A. Iscom, a novel structure for antigenic presentation of membrane proteins from enveloped viruses. 1984 Mar 29-Apr 4Nature. 308(5958):457–460. doi: 10.1038/308457a0. [DOI] [PubMed] [Google Scholar]
  15. Mowat A. M., Lamont A. G., Bruce M. G. A genetically determined lack of oral tolerance to ovalbumin is due to failure of the immune system to respond to intestinally derived tolerogen. Eur J Immunol. 1987 Nov;17(11):1673–1676. doi: 10.1002/eji.1830171126. [DOI] [PubMed] [Google Scholar]
  16. Osterhaus A., Weijer K., UytdeHaag F., Knell P., Jarrett O., Akerblom L., Morein B. Serological responses in cats vaccinated with FeLV ISCOM and an inactivated FeLV vaccine. Vaccine. 1989 Apr;7(2):137–141. doi: 10.1016/0264-410x(89)90053-4. [DOI] [PubMed] [Google Scholar]
  17. Osterhaus A., Weijer K., Uytdehaag F., Jarrett O., Sundquist B., Morein B. Induction of protective immune response in cats by vaccination with feline leukemia virus iscom. J Immunol. 1985 Jul;135(1):591–596. [PubMed] [Google Scholar]
  18. Sprent J., Webb S. R. Function and specificity of T cell subsets in the mouse. Adv Immunol. 1987;41:39–133. doi: 10.1016/s0065-2776(08)60030-9. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Trudel M., Boulay G., Séguin C., Nadon F., Lussier G. Control of infectious bovine rhinotracheitis in calves with a BHV-1 subunit-ISCOM vaccine. Vaccine. 1988 Dec;6(6):525–529. doi: 10.1016/0264-410x(88)90105-3. [DOI] [PubMed] [Google Scholar]
  22. Wraith D. C., Askonas B. A. Induction of influenza A virus cross-reactive cytotoxic T cells by a nucleoprotein/haemagglutinin preparation. J Gen Virol. 1985 Jun;66(Pt 6):1327–1331. doi: 10.1099/0022-1317-66-6-1327. [DOI] [PubMed] [Google Scholar]
  23. Yewdell J. W., Bennink J. R., Hosaka Y. Cells process exogenous proteins for recognition by cytotoxic T lymphocytes. Science. 1988 Feb 5;239(4840):637–640. doi: 10.1126/science.3257585. [DOI] [PubMed] [Google Scholar]
  24. de Vries P., van Binnendijk R. S., van der Marel P., van Wezel A. L., Voorma H. O., Sundquist B., Uytdehaag F. G., Osterhaus A. D. Measles virus fusion protein presented in an immune-stimulating complex (iscom) induces haemolysis-inhibiting and fusion-inhibiting antibodies, virus-specific T cells and protection in mice. J Gen Virol. 1988 Mar;69(Pt 3):549–559. doi: 10.1099/0022-1317-69-3-549. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES