Abstract
The immune responses of sporozoite-immunized rodents and of human volunteers exposed to multiple bites of irradiated Plasmodium falciparum infected mosquitos have been investigated using a yeast-derived recombinant P. falciparum circumsporozoite (rPfCS) protein. The murine immune response to immunization with rPfCS was not genetically restricted. Nine different murine haplotypes, when immunized with rPfCS, developed high levels of antisporozoite antibodies detectable by IFA and RIA. In addition, injection of rPfCS induced a secondary antibody response in P. falciparum sporozoite-primed mice. Murine T-cell epitopes were mapped in the C terminus of the rPfCS protein using overlapping synthetic peptides. The human T-cell response was investigated using T-cell clones derived from peripheral blood lymphocytes (PBL) of a P. falciparum sporozoite-immunized volunteer. A total of 40 CD4+ T-cell clones were obtained. Stimulation indices ranged from 2.5 to 103.4 following challenge with rPfCS in the presence, but not in the absence, of antigen-presenting cells. The clones were specific for rPfCs and did not proliferate or secrete lymphokines when challenged with yeast-derived recombinant P. vivax or P. berghei CS protein or with a yeast-extract control. The clones also recognized the native CS protein in extracts of P. falciparum, but not P. berghei or P. cynomolgi, sporozoites.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Gillis S., Smith K. A. Long term culture of tumour-specific cytotoxic T cells. Nature. 1977 Jul 14;268(5616):154–156. doi: 10.1038/268154a0. [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]
- Sinigaglia F., Matile H., Pink J. R. Plasmodium falciparum-specific human T cell clones: evidence for helper and cytotoxic activities. Eur J Immunol. 1987 Feb;17(2):187–192. doi: 10.1002/eji.1830170206. [DOI] [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]
- 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]