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. 1990;68(Suppl):80–84.

Evidence implicating MHC genes in the immunological nonresponsiveness to the Plasmodium falciparum CS protein.

M F Good 1, S Kumar 1, A S De Groot 1, W R Weiss 1, I A Quakyi 1, F Dontfraid 1, G E Smith 1, M Cochran 1, J A Berzofsky 1, L H Miller 1
PMCID: PMC2393035  PMID: 1709836

Abstract

The circumsporozoite (CS) protein is a major candidate vaccine antigen for the sporozoite stage of malaria. Both cytotoxic T cells (CTL) and antibody specific for the CS protein are thought to be important in protection. By examining the immune response in mice and humans we have shown that genes mapping to the major histocompatibility complex (MHC) are important for immune responsiveness. F1 mice between high antibody responders and low antibody responders are high antibody responders, suggesting that in this model immune suppressor genes do not control the immune response. Using synthetic peptides to map epitopes for CTL and helper T cells (which are important for the antibody response) we have shown that the T-cell epitopes are located in the polymorphic region of the protein, and we hypothesize that T cells have indeed selected the variation observed in the CS protein. The success of subunit vaccines will depend on the pattern of variation in different geographical locations, the ability to construct multivalent vaccines containing different variant epitopes from this protein, and on the existence of other sporozoite and liver-stage proteins involved in protection.

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Selected References

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

  1. Ballou W. R., Hoffman S. L., Sherwood J. A., Hollingdale M. R., Neva F. A., Hockmeyer W. T., Gordon D. M., Schneider I., Wirtz R. A., Young J. F. Safety and efficacy of a recombinant DNA Plasmodium falciparum sporozoite vaccine. Lancet. 1987 Jun 6;1(8545):1277–1281. doi: 10.1016/s0140-6736(87)90540-x. [DOI] [PubMed] [Google Scholar]
  2. Bennink J. R., Yewdell J. W. Murine cytotoxic T lymphocyte recognition of individual influenza virus proteins. High frequency of nonresponder MHC class I alleles. J Exp Med. 1988 Nov 1;168(5):1935–1939. doi: 10.1084/jem.168.5.1935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen D. H., Tigelaar R. E., Weinbaum F. I. Immunity to sporozoite-induced malaria infeciton in mice. I. The effect of immunization of T and B cell-deficient mice. J Immunol. 1977 Apr;118(4):1322–1327. [PubMed] [Google Scholar]
  4. Clyde D. F., Most H., McCarthy V. C., Vanderberg J. P. Immunization of man against sporozite-induced falciparum malaria. Am J Med Sci. 1973 Sep;266(3):169–177. doi: 10.1097/00000441-197309000-00002. [DOI] [PubMed] [Google Scholar]
  5. Good M. F., Berzofsky J. A., Maloy W. L., Hayashi Y., Fujii N., Hockmeyer W. T., Miller L. H. Genetic control of the immune response in mice to a Plasmodium falciparum sporozoite vaccine. Widespread nonresponsiveness to single malaria T epitope in highly repetitive vaccine. J Exp Med. 1986 Aug 1;164(2):655–660. doi: 10.1084/jem.164.2.655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Good M. F., Kumar S., Miller L. H. The real difficulties for malaria sporozoite vaccine development: nonresponsiveness and antigenic variation. Immunol Today. 1988 Nov;9(11):351–355. doi: 10.1016/0167-5699(88)91336-9. [DOI] [PubMed] [Google Scholar]
  7. Good M. F., Maloy W. L., Lunde M. N., Margalit H., Cornette J. L., Smith G. L., Moss B., Miller L. H., Berzofsky J. A. Construction of synthetic immunogen: use of new T-helper epitope on malaria circumsporozoite protein. Science. 1987 Feb 27;235(4792):1059–1062. doi: 10.1126/science.2434994. [DOI] [PubMed] [Google Scholar]
  8. Good M. F., Miller L. H., Kumar S., Quakyi I. A., Keister D., Adams J. H., Moss B., Berzofsky J. A., Carter R. Limited immunological recognition of critical malaria vaccine candidate antigens. Science. 1988 Oct 28;242(4878):574–577. doi: 10.1126/science.2902690. [DOI] [PubMed] [Google Scholar]
  9. Good M. F., Pombo D., Quakyi I. A., Riley E. M., Houghten R. A., Menon A., Alling D. W., Berzofsky J. A., Miller L. H. Human T-cell recognition of the circumsporozoite protein of Plasmodium falciparum: immunodominant T-cell domains map to the polymorphic regions of the molecule. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1199–1203. doi: 10.1073/pnas.85.4.1199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hoffman S. L., Oster C. N., Plowe C. V., Woollett G. R., Beier J. C., Chulay J. D., Wirtz R. A., Hollingdale M. R., Mugambi M. Naturally acquired antibodies to sporozoites do not prevent malaria: vaccine development implications. Science. 1987 Aug 7;237(4815):639–642. doi: 10.1126/science.3299709. [DOI] [PubMed] [Google Scholar]
  11. Kumar S., Miller L. H., Quakyi I. A., Keister D. B., Houghten R. A., Maloy W. L., Moss B., Berzofsky J. A., Good M. F. Cytotoxic T cells specific for the circumsporozoite protein of Plasmodium falciparum. Nature. 1988 Jul 21;334(6179):258–260. doi: 10.1038/334258a0. [DOI] [PubMed] [Google Scholar]
  12. Potocnjak P., Yoshida N., Nussenzweig R. S., Nussenzweig V. Monovalent fragments (Fab) of monoclonal antibodies to a sporozoite surface antigen (Pb44) protect mice against malarial infection. J Exp Med. 1980 Jun 1;151(6):1504–1513. doi: 10.1084/jem.151.6.1504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Rothbard J. B., Taylor W. R. A sequence pattern common to T cell epitopes. EMBO J. 1988 Jan;7(1):93–100. doi: 10.1002/j.1460-2075.1988.tb02787.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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. Oral Salmonella typhimurium vaccine expressing circumsporozoite protein protects against malaria. Science. 1988 Apr 15;240(4850):336–338. doi: 10.1126/science.3281260. [DOI] [PubMed] [Google Scholar]
  15. Schofield L., Villaquiran J., Ferreira A., Schellekens H., Nussenzweig R., Nussenzweig V. Gamma interferon, CD8+ T cells and antibodies required for immunity to malaria sporozoites. Nature. 1987 Dec 17;330(6149):664–666. doi: 10.1038/330664a0. [DOI] [PubMed] [Google Scholar]
  16. de Groot A. S., Johnson A. H., Maloy W. L., Quakyi I. A., Riley E. M., Menon A., Banks S. M., Berzofsky J. A., Good M. F. Human T cell recognition of polymorphic epitopes from malaria circumsporozoite protein. J Immunol. 1989 Jun 1;142(11):4000–4005. [PubMed] [Google Scholar]
  17. de la Cruz V. F., Maloy W. L., Miller L. H., Lal A. A., Good M. F., McCutchan T. F. Lack of cross-reactivity between variant T cell determinants from malaria circumsporozoite protein. J Immunol. 1988 Oct 1;141(7):2456–2460. [PubMed] [Google Scholar]

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