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Immunogenicity of a hybrid Plasmodium falciparum, malaria antigen

Published online by Cambridge University Press:  06 April 2009

M. J. Lockyer
Affiliation:
Department of Cell Biology, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3BS
H. Cooper
Affiliation:
Department of Cell Biology, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3BS
J. Tite
Affiliation:
Department of Cell Biology, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3BS
W. Rowan
Affiliation:
Department of Cell Biology, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3BS
J. S. Crowe
Affiliation:
Department of Cell Biology, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3BS

Summary

A recombinant baculovirus-expressed hybrid protein containing epitopes for the C-terminal fragment of the Plasmodium falciparum precursor to the major merozoite surface antigens (PMMSA) and the tetrapeptide repeats of the circumsporozoite protein (CSP) was assessed for its immunogenicity. Murine MHC-II restriction of the antibody response to the CSP repeats was not overcome by the PMMSA component, the response to which showed no restriction. In an adjuvant trial the highest antibody titres in rabbits to both components of the hybrid were obtained using Freund's adjuvant. Lack of a boosting antibody response to the CSP repeats appeared to be linked to the conformation of the PMMSA component. Formulation of the hybrid protein into Iscoms gave antibody titres of only short duration to both components.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1993

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References

REFERENCES

Allison, A. C. & Byars, N. E. (1986). An adjuvant formulation that selectively elicits the formation of antibodies of protective isotypes and of cell-mediated immunity. Journal of Immunological Methods 95, 157–68.CrossRefGoogle ScholarPubMed
Chang, S. P., Hui, G. S. N., Kato, A. & Siddiqui, W. A. (1989). Generalized immunological recognition of the major merozoite surface antigen (gp195) of Plasmodium falciparum. Proceedings of the National Academy of Sciences, USA 86, 6343–7.CrossRefGoogle ScholarPubMed
Crowe, J. S., Lamont, A., Barry, J. D. & Vickerman, K. (1984). Cytotoxicity of monoclonal antibodies to Trypanosoma brucei. Transactions of the Royal Society of Tropical Medicine and Hygiene 78, 508–13.CrossRefGoogle ScholarPubMed
Del Giudice, G., Cooper, J. A., Merino, J., Verdini, A. S., Pessi, A., Togna, A. R., Engers, H. D., Corradin, G. & Lambert, P.-H. (1986). The antibody response in mice to carrier-free synthetic polymers of Plasmodium falciparum circumsporozoite repetitive epitope is I-Ab restricted: implications for malaria vaccines. Journal of Immunology 137, 2952–5.CrossRefGoogle ScholarPubMed
Etlinger, H. M., Caspers, P., Matile, H., Schoenfeld, H. J., Stueber, D. & Takacs, B. (1991). Ability of recombinant or native proteins to protect monkeys against heterologous challenge with Plasmodium falciparum. Infection and Immunity 59, 3498–503.CrossRefGoogle ScholarPubMed
Good, M. F., Berzofsky, J. A., Maloy, W. L., Hayaski, Y., Fujii, N., Hockmeyer, W. T. & Miller, L. H. (1986). Genetic control of the immune response in mice to Plasmodium falciparum sporozoite vaccine. Widespread non-responsiveness to single malaria T epitope in highly repetitive vaccine. Journal of Experimental Medicine 164, 655–60.CrossRefGoogle 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. (1987). Construction of synthetic immunogen: use of new T-helper epitope on malaria circumsporozoite protein. Science 235, 1059–62.CrossRefGoogle ScholarPubMed
Holder, A. A., Lockyer, M. J. & Hardy, G. W. (1988). A hybrid gene to express protein epitopes from both sporozoite and merozoite surface antigens of Plasmodium falciparum. Parasitology 97, 373–82.CrossRefGoogle ScholarPubMed
Holder, A. A., Sandhu, J. S., Hillman, Y., Davey, L. S., Nicholls, S. C., Cooper, H. & Lockyer, M. J. (1987). Processing of the precursor to the major merozoite surface antigens of Plasmodium falciparum. Parasitology 94, 199208.CrossRefGoogle Scholar
Kearney, J. P., Radbruch, A., Liesegang, B. & Rajewsky, K. (1979). A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreted hybrid cell lines. Journal of Immunology 123, 1548–50.CrossRefGoogle Scholar
Lockyer, M. J., Marsh, K. & Newbold, C. J. (1989). Wild isolates of Plasmodium falciparum show extensive polymorphism in T-cell epitopes of the circumsporozoite protein. Molecular and Biochemical Parasitology 37, 275–80.CrossRefGoogle ScholarPubMed
Londono, J. A., Gras-Masse, H., Dubeaux, C., Tartar, A. & Druilhe, P. (1990). Secondary structure and immunogenicity of hybrid synthetic peptides derived from two Plasmodium falciparum pre-erythrocytic antigens. Journal of Immunology 145, 1557–63.CrossRefGoogle ScholarPubMed
Morein, B., Lovgren, K. & Hoglund, S. (1989). Immunostimulating complex (ISCOM). In Immunological Adjuvants and Vaccines, vol. 179 (ed. Gregoriadis, G., Allison, A. C. & Poste, G.), pp. 153161. New York and London: Plenum Press.CrossRefGoogle Scholar
Murphy, V. F., Rowan, W. C., Page, M. J. & Holder, A. A. (1990). Expression of hybrid malaria antigens in insect cells and their engineering for correct folding and secretion. Parasitology 100, 177–83.CrossRefGoogle ScholarPubMed
Patarroyo, M. E., Amador, P. J., Moreno, A., Guzman, F., Romero, P., Tascon, R., Franco, A., Murillo, L. A., Ponton, G. & Trujillo, G. (1988). A synthetic vaccine protects humans against challenge with asexual blood Stages of Plasmodium falciparum malaria. Nature, London 332, 158–61.CrossRefGoogle ScholarPubMed
Rodriguez, R., Moreno, A., Guzman, F., Calvo, M. & Patarroyo, M. E. (1990). Studies in owl monkeys leading to the development of a synthetic vaccine against the asexual blood stages of Plasmodium falciparum. American Journal of Tropical Medicine and Hygiene 43, 339–54.CrossRefGoogle Scholar
Ruebush, T. K., Campbell, G. H., Moreno, A., Patarroyo, M. E. & Collins, W. E. (1990). Immunization of owl monkeys with a combination of Plasmodium falciparum asexual blood-stage synthetic peptides. American Journal of Tropical Medicine and Hygiene 43, 355–66.CrossRefGoogle Scholar
Rzepczyk, C. M., Csurhes, P. A., Lord, R. & Matile, H. (1990). Synthetic peptide immunogens eliciting antibodies to Plasmodium falciparum sporozoite and merozoite surface antigens in H-2b and H-2k mice. Journal of Immunology 145, 2691–6.CrossRefGoogle ScholarPubMed
Summers, M. D. & Smith, G. E. (1987). A Manual of Methods for Baculovirus Vectors and Insect Cell Culture Procedures. Texas Agricultural Experimental Station Bulletin no. 1555.Google Scholar
Togna, A. R., Del Giudice, G., Verdini, A. S., Bonelli, F., Pessi, A., Engers, H. D. & Corradin, G. (1986). Synthetic Plasmodium falciparum circumsporozoite peptides elicit heterogeneous L3T4+ Tcell proliferative responses in 11–2b mice. Journal of Immunology 137, 2956–60.CrossRefGoogle Scholar