Influence of age and HLA type on interferon‐gamma (IFN‐γ) responses to a naturally occurring polymorphic epitope of Plasmodium falciparum liver stage antigen‐1 (LSA‐1)

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‐γ 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‐γ ELISPOT responses increased with age in malaria‐exposed subjects: 14–16% and 30–36% of 2–5‐ and 6–54‐year‐olds, respectively, had ≥ 10 IFN‐γ‐secreting cells/106 peripheral blood mononuclear cells when stimulated with at least one peptide variant (P