Identification of T-cell determinants in natural immune responses to the Plasmodium falciparum apical membrane antigen (AMA-1) in an adult population exposed to malaria.
AMA-1 of Plasmodium falciparum is a promising candidate antigen in malaria vaccine development. In this study, we have mapped the immunodominant T-cell determinants in this antigen by using synthetic peptides. From the amphipathic scores, 17 putative T-cell determinants were identified. Nine of the 17 peptides complementary to the putative T-cell determinants induced proliferation of peripheral blood mononuclear cells (PBMC) from Kenyan residents who had lifelong exposure to malaria; none of these peptides induced proliferation of PBMC from donors who were not previously exposed to malaria. This indicates that AMA-1 peptides were stimulating T cells that were previously primed by prior exposure to P. falciparum. Many positive responders showed reactivity to more than one peptide, and some of the potent proliferative T epitopes were found to be localized in the highly conserved regions of AMA-1, suggesting that it may be possible to induce T-cell memory that can recognize different variant forms of the parasite. This information on the natural immune responses against the AMA-1 vaccine antigen in clinically immune adults will be helpful in the development of an AMA-1 antigen-based malaria vaccine and may also guide testing of AMA-1-based vaccine formulations.
Lal
A A
AA
Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, U. S. Department of Health and Human Services, Atlanta, Georgia 30341-3717, USA
Hughes
M A
MA
Oliveira
D A
DA
Nelson
C
C
Bloland
P B
PB
Oloo
A J
AJ
Hawley
W E
WE
Hightower
A W
AW
Nahlen
B L
BL
Udhayakumar
V
V
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D000939:Epitopes; D006801:Humans; D007113:Immunity, Innate; D008213:Lymphocyte Activation; D008288:Malaria / Q000276:immunology*; D017780:Malaria Vaccines / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000953:Antigens, Protozoan; D000939:Epitopes; D017780:Malaria Vaccines; D008565:Membrane Proteins; D010446:Peptide Fragments; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium