Cytotoxic T-Lymphocyte Epitopes for HLA-B53 and Other HLA Types in the Malaria Vaccine Candidate Liver-Stage Antigen 3
Aidoo M., Lalvani A., Gilbert SC., Hu JT., Daubersies P., Hurt N., Whittle HC., Druihle P., Hill AVS.
ABSTRACT The development of an effective preerythrocytic vaccine againstPlasmodium 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.