Abstract
The design of a subunit vaccine against the malaria parasite relies on the epitopes recognized by T cells being identified and polymorphisms therein being defined. Here we present the analysis of a 354-bp fragment of the circumsporozoite (CS) protein encompassing defined proliferative and cytotoxic T-cell recognition regions. We reveal that the polymorphism of CS protein T-cell sites appears to be very limited among Plasmodium falciparum isolates prevalent in certain geographical regions, in particular Papua New Guinea. Furthermore, the more extensive polymorphism noted in other areas appears to be restricted. Although the extent of variation observed for the T-cell recognition domains suggests that any vaccine designed to stimulate this form of immunity will need to be polyvalent, this variation appears to be finite and the combination of peptides necessary for inclusion in a polyvalent vaccine may be small. If ways to increase immune responsiveness can be found, then a vaccine designed to stimulate CS protein-specific T-cell activity may prevent malaria.
Full text
PDF







Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anders R. F., Brown G. V., Edwards A. Characterization of an S antigen synthesized by several isolates of Plasmodium falciparum. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6652–6656. doi: 10.1073/pnas.80.21.6652. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Arnot D. Malaria and the major histocompatibility complex. Parasitol Today. 1989 May;5(5):138–142. doi: 10.1016/0169-4758(89)90077-x. [DOI] [PubMed] [Google Scholar]
- Burkot T. R., Williams J. L., Schneider I. Infectivity to mosquitoes of Plasmodium falciparum clones grown in vitro from the same isolate. Trans R Soc Trop Med Hyg. 1984;78(3):339–341. doi: 10.1016/0035-9203(84)90114-7. [DOI] [PubMed] [Google Scholar]
- Caspers P., Gentz R., Matile H., Pink J. R., Sinigaglia F. The circumsporozoite protein gene from NF54, a Plasmodium falciparum isolate used in malaria vaccine trials. Mol Biochem Parasitol. 1989 Jun 15;35(2):185–189. doi: 10.1016/0166-6851(89)90121-7. [DOI] [PubMed] [Google Scholar]
- Chang S. P., Kramer K. J., Yamaga K. M., Kato A., Case S. E., Siddiqui W. A. Plasmodium falciparum: gene structure and hydropathy profile of the major merozoite surface antigen (gp195) of the Uganda-Palo Alto isolate. Exp Parasitol. 1988 Oct;67(1):1–11. doi: 10.1016/0014-4894(88)90002-1. [DOI] [PubMed] [Google Scholar]
- Chen P., Lamont G., Elliott T., Kidson C., Brown G., Mitchell G., Stace J., Alpers M. Plasmodium falciparum strains from Papua New Guinea: culture characteristics and drug sensitivity. Southeast Asian J Trop Med Public Health. 1980 Dec;11(4):435–440. [PubMed] [Google Scholar]
- Dame J. B., Williams J. L., McCutchan T. F., Weber J. L., Wirtz R. A., Hockmeyer W. T., Maloy W. L., Haynes J. D., Schneider I., Roberts D. Structure of the gene encoding the immunodominant surface antigen on the sporozoite of the human malaria parasite Plasmodium falciparum. Science. 1984 Aug 10;225(4662):593–599. doi: 10.1126/science.6204383. [DOI] [PubMed] [Google Scholar]
- De La Cruz V. F., Maloy W. L., Miller L. H., Good M. F., McCutchan T. F. The immunologic significance of variation within malaria circumsporozoite protein sequences. J Immunol. 1989 May 15;142(10):3568–3575. [PubMed] [Google Scholar]
- Dontfraid F., Cochran M. A., Pombo D., Knell J. D., Quakyi I. A., Kumar S., Houghten R. A., Berzofsky J. A., Miller L. H., Good M. F. Human and murine CD4 T cell epitopes map to the same region of the malaria circumsporozoite protein: limited immunogenicity of sporozoites and circumsporozoite protein. Mol Biol Med. 1988 Dec;5(3):185–196. [PubMed] [Google Scholar]
- Doolan D. L., Houghten R. A., Good M. F. Location of human cytotoxic T cell epitopes within a polymorphic domain of the Plasmodium falciparum circumsporozoite protein. Int Immunol. 1991 Jun;3(6):511–516. doi: 10.1093/intimm/3.6.511. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Graves P. M., Carter R., Keystone J. S., Seeley D. C., Jr Drug sensitivity and isoenzyme type in cloned lines of Plasmodium falciparum. Am J Trop Med Hyg. 1984 Mar;33(2):212–219. doi: 10.4269/ajtmh.1984.33.212. [DOI] [PubMed] [Google Scholar]
- Guttinger M., Caspers P., Takacs B., Trzeciak A., Gillessen D., Pink J. R., Sinigaglia F. Human T cells recognize polymorphic and non-polymorphic regions of the Plasmodium falciparum circumsporozoite protein. EMBO J. 1988 Aug;7(8):2555–2558. doi: 10.1002/j.1460-2075.1988.tb03104.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gysin J., Hommel M., da Silva L. P. Experimental infection of the squirrel monkey (Saimiri sciureus) with Plasmodium falciparum. J Parasitol. 1980 Dec;66(6):1003–1009. [PubMed] [Google Scholar]
- Holder A. A., Freeman R. R. Biosynthesis and processing of a Plasmodium falciparum schizont antigen recognized by immune serum and a monoclonal antibody. J Exp Med. 1982 Nov 1;156(5):1528–1538. doi: 10.1084/jem.156.5.1528. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Limpaiboon T., Shirley M. W., Kemp D. J., Saul A. 7H8/6, a multicopy DNA probe for distinguishing isolates of Plasmodium falciparum. Mol Biochem Parasitol. 1991 Aug;47(2):197–206. doi: 10.1016/0166-6851(91)90179-a. [DOI] [PubMed] [Google Scholar]
- Lockyer M. J., Marsh K., Newbold C. I. Wild isolates of Plasmodium falciparum show extensive polymorphism in T cell epitopes of the circumsporozoite protein. Mol Biochem Parasitol. 1989 Dec;37(2):275–280. doi: 10.1016/0166-6851(89)90159-x. [DOI] [PubMed] [Google Scholar]
- Lockyer M. J., Schwarz R. T. Strain variation in the circumsporozoite protein gene of Plasmodium falciparum. Mol Biochem Parasitol. 1987 Jan 2;22(1):101–108. doi: 10.1016/0166-6851(87)90073-9. [DOI] [PubMed] [Google Scholar]
- Malik A., Egan J. E., Houghten R. A., Sadoff J. C., Hoffman S. L. Human cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3300–3304. doi: 10.1073/pnas.88.8.3300. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McBride J. S., Newbold C. I., Anand R. Polymorphism of a high molecular weight schizont antigen of the human malaria parasite Plasmodium falciparum. J Exp Med. 1985 Jan 1;161(1):160–180. doi: 10.1084/jem.161.1.160. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCutchan T. F., Waters A. P. Mutations with multiple independent origins in surface antigens mark the targets of biological selective pressure. Immunol Lett. 1990 Aug;25(1-3):23–26. doi: 10.1016/0165-2478(90)90085-5. [DOI] [PubMed] [Google Scholar]
- Peterson M. G., Coppel R. L., McIntyre P., Langford C. J., Woodrow G., Brown G. V., Anders R. F., Kemp D. J. Variation in the precursor to the major merozoite surface antigens of Plasmodium falciparum. Mol Biochem Parasitol. 1988 Jan 15;27(2-3):291–301. doi: 10.1016/0166-6851(88)90049-7. [DOI] [PubMed] [Google Scholar]
- Ponnudurai T., Meuwissen J. H., Leeuwenberg A. D., Verhave J. P., Lensen A. H. The production of mature gametocytes of Plasmodium falciparum in continuous cultures of different isolates infective to mosquitoes. Trans R Soc Trop Med Hyg. 1982;76(2):242–250. doi: 10.1016/0035-9203(82)90289-9. [DOI] [PubMed] [Google Scholar]
- Rodrigues M. M., Cordey A. S., Arreaza G., Corradin G., Romero P., Maryanski J. L., Nussenzweig R. S., Zavala F. CD8+ cytolytic T cell clones derived against the Plasmodium yoelii circumsporozoite protein protect against malaria. Int Immunol. 1991 Jun;3(6):579–585. doi: 10.1093/intimm/3.6.579. [DOI] [PubMed] [Google Scholar]
- Romero P., Maryanski J. L., Corradin G., Nussenzweig R. S., Nussenzweig V., Zavala F. Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria. Nature. 1989 Sep 28;341(6240):323–326. doi: 10.1038/341323a0. [DOI] [PubMed] [Google Scholar]
- Tanabe K., Mackay M., Goman M., Scaife J. G. Allelic dimorphism in a surface antigen gene of the malaria parasite Plasmodium falciparum. J Mol Biol. 1987 May 20;195(2):273–287. doi: 10.1016/0022-2836(87)90649-8. [DOI] [PubMed] [Google Scholar]
- Thaithong S., Beale G. H., Fenton B., McBride J., Rosario V., Walker A., Walliker D. Clonal diversity in a single isolate of the malaria parasite Plasmodium falciparum. Trans R Soc Trop Med Hyg. 1984;78(2):242–245. doi: 10.1016/0035-9203(84)90287-6. [DOI] [PubMed] [Google Scholar]
- Walliker D., Quakyi I. A., Wellems T. E., McCutchan T. F., Szarfman A., London W. T., Corcoran L. M., Burkot T. R., Carter R. Genetic analysis of the human malaria parasite Plasmodium falciparum. Science. 1987 Jun 26;236(4809):1661–1666. doi: 10.1126/science.3299700. [DOI] [PubMed] [Google Scholar]
- Weiss W. R., Mellouk S., Houghten R. A., Sedegah M., Kumar S., Good M. F., Berzofsky J. A., Miller L. H., Hoffman S. L. Cytotoxic T cells recognize a peptide from the circumsporozoite protein on malaria-infected hepatocytes. J Exp Med. 1990 Mar 1;171(3):763–773. doi: 10.1084/jem.171.3.763. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yoshida N., Di Santi S. M., Dutra A. P., Nussenzweig R. S., Nussenzweig V., Enea V. Plasmodium falciparum: restricted polymorphism of T cell epitopes of the circumsporozoite protein in Brazil. Exp Parasitol. 1990 Nov;71(4):386–392. doi: 10.1016/0014-4894(90)90064-j. [DOI] [PubMed] [Google Scholar]
- Zevering Y., Houghten R. A., Frazer I. H., Good M. F. Major population differences in T cell response to a malaria sporozoite vaccine candidate. Int Immunol. 1990;2(10):945–955. doi: 10.1093/intimm/2.10.945. [DOI] [PubMed] [Google Scholar]
- 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]
- de la Cruz V. F., Lal A. A., McCutchan T. F. Sequence variation in putative functional domains of the circumsporozoite protein of Plasmodium falciparum. Implications for vaccine development. J Biol Chem. 1987 Sep 5;262(25):11935–11939. [PubMed] [Google Scholar]
- 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]
- del Portillo H. A., Nussenzweig R. S., Enea V. Circumsporozoite gene of a Plasmodium falciparum strain from Thailand. Mol Biochem Parasitol. 1987 Jul;24(3):289–294. doi: 10.1016/0166-6851(87)90161-7. [DOI] [PubMed] [Google Scholar]