Cytotoxic T-lymphocyte epitopes for HLA-B53 and other HLA types in the malaria vaccine candidate liver-stage antigen 3.
The development of an effective preerythrocytic vaccine against Plasmodium falciparum malaria is likely to require inclusion of components from several preerythrocytic antigens. The association of HLA-B53 with resistance to severe malaria in West Africa provided evidence that HLA class I-restricted CD8(+) T-cell responses play a role in protective immunity in African children, supporting data from rodent models of malaria. Previously, a single epitope from liver-stage-specific antigen 1 (LSA-1) has been shown to be recognized by HLA-B53-specific cytotoxic T lymphocytes (CTL), but HLA-B53 epitopes were not found in four other antigens. In this study we measured CTL responses to peptides from the recently sequenced antigen liver-stage antigen 3 (LSA-3) and identified in it a new epitope restricted by HLA-B53. Several CTL epitopes restricted by other class I types were also identified within LSA-3 in studies in The Gambia and Tanzania. CTL were also identified to an additional P. falciparum antigen, exported protein 1 (Exp-1), the homologue of which is a protective antigen in a rodent model of malaria. These findings emphasize the diversity of P. falciparum antigens recognized by CD8(+) T cells in humans and support the inclusion of components from several antigens in new CTL-inducing vaccines against malaria.
Aidoo
M
M
Molecular Immunology Group, Institute of Molecular Medicine, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom. Mha3@cdc.gov
Lalvani
A
A
Gilbert
S C
SC
Hu
J T
JT
Daubersies
P
P
Hurt
N
N
Whittle
H C
HC
Druihle
P
P
Hill
A V
AV
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D015795:HLA-B8 Antigen / Q000276:immunology; D006801:Humans; D008099:Liver / Q000469:parasitology; D008288:Malaria / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000953:Antigens, Protozoan; D017931:DNA Primers; D000939:Epitopes; D006680:HLA Antigens; D015789:HLA-A2 Antigen; C078438:HLA-B53 antigen; D015795:HLA-B8 Antigen; D017780:Malaria Vaccines; C067302:liver stage-specific antigen, Plasmodium