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Antigenic polymorphism and HLA restriction may limit the immunogenicity of a subunit vaccine against liver-stage Plasmodium falciparum. We examined 59 clinical isolates and five laboratory clones of P. falciparum for polymorphism in the N- and C-terminal regions of LSA-1, evaluated binding of the corresponding peptides to selected HLA class I alleles, and measured IFN-gamma responses in residents of a malaria-endemic area of Papua New Guinea where HLA-A*1101, -24, -B13, and -B40 are the most common class I alleles. LSA-1 polymorphism was limited to a single non-synonymous mutation encoding serine (S), proline (P), or threonine (T) at amino acid 85. Nine-mer 84-92 peptides with S, T, or P at the primary anchor position bound differentially to HLA-A11, -A2, and -B7. IFN-gamma ELISPOT responses increased with age in malaria-exposed subjects: 14-16% and 30-36% of 2-5- and 6-54-year-olds, respectively, had > or =10 IFN-gamma-secreting cells/106 peripheral blood mononuclear cells when stimulated with at least one peptide variant (P<0.05). IFN-gamma responses to all three peptides were also greater for older than younger individuals. No children < 3 years old had lymphocytes that responded to all three 84-92 peptides, whereas 45% of adults (mean age 48 years) had aggregated IFN-gamma responses. These data support the notion that age-related cumulative exposure to P. falciparum increases the frequency of IFN-gamma responses to polymorphic epitopes of liver-stage antigens such as LSA-1.

Original publication

DOI

10.1046/j.1365-2249.2000.01346.x

Type

Journal

Clinical and experimental immunology

Publication Date

10/2000

Volume

122

Pages

94 - 100

Addresses

Division of Geographic Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4983, USA.

Keywords

Animals, Humans, Plasmodium falciparum, Malaria, Falciparum, Peptides, Antigens, Protozoan, HLA-A Antigens, HLA-A2 Antigen, HLA-B Antigens, Epitopes, T-Lymphocyte, Histocompatibility Testing, Antigenic Variation, Aging, Alleles, Adolescent, Adult, Middle Aged, Child, Child, Preschool, Papua New Guinea, Interferon-gamma, HLA-A11 Antigen