Major population differences in T cell response to a malaria sporozoite vaccine candidate.
Using a complete series of overlapping peptides, we have identified the T cell epitopes of a malaria vaccine candidate, the circumsporozoite (CS) protein, that are recognized by sporozoite-exposed residents of a non-endemic country. This protein and subunits from it are being considered as malaria sporozoite vaccine candidates, as CS-specific antibodies and cytotoxic T lymphocytes have been shown to have a role in protection. The rationale for developing an antibody-based vaccine is that in Plasmodium falciparum the immunodominant B cell epitope of the protein, (Asn-Ala-Asn-Pro)n [(NANP)n], is invariant. However, the ideal vaccine must contain CS protein-derived T cell antigenic epitopes to allow natural boosting of the antibody response following sporozoite exposure. Here, we show that major differences occur between the CS-specific T cell responses of non-endemic Caucasians and an endemic African population. HLA differences between the populations are, in part, responsible. Subunit malaria vaccines for one population may be ineffective in a different population.
Zevering
Y
Y
Tropical Health Program, Queensland Institute of Medical Research, Herston, Bisbane, Australia.
Houghten
R A
RA
Frazer
I H
IH
Good
M F
MF
D000818:Animals; D006801:Humans; D000595:Amino Acid Sequence; D000953:Antigens, Protozoan / Q000737:chemistry; D000939:Epitopes / Q000737:chemistry; D006680:HLA Antigens; D008213:Lymphocyte Activation; D008288:Malaria / Q000276:immunology / Q000517:prevention & control; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology; D016052:Protozoan Vaccines / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D044465:White People
D000953:Antigens, Protozoan; C041595:circumsporozoite protein, Protozoan; D000939:Epitopes; D006680:HLA Antigens; D010455:Peptides; D015800:Protozoan Proteins; D016052:Protozoan Vaccines