The efficacy of a
malaria peptide vaccine would be enhanced by the inclusion of a parasite-derived universal
T cell epitope to ensure that all vaccinees develop parasite-specific cellular and humoral immunity. Two circumsporozoite (CS)
protein T cell epitopes, previously identified by CD4+ T cell clones derived from Plasmodium falciparum sporozoite-immunized volunteers, were studied to determine their HLA class II binding potential. One
epitope, located in
amino acid (aa) 326-345 of the P. falciparum (NF54 strain) CS
protein, was "universal" in that it could bind to multiple DR and DQ molecules in vitro. In contrast, the second
epitope, T1, which is located in the CS repeat region, was recognized by T cells in the context of DQ6 (DQB1*0603) and did not bind with high affinity to any of the class II molecules tested in the
peptide binding assays. The in vitro patterns of
peptide/HLA interactions correlated with immunogenicity in vivo. A multiple
antigen peptide (MAP) containing the aa 326-345
epitope elicited responses in eight inbred strains (H-2(a,b,d,k,p,q,r,s)), while the T1 MAP was recognized by only a single haplotype, H-2b. The combination of the universal aa 326-345
T cell epitope and the T1 repeat in a di-
epitope MAP overcame the genetic restriction to the P. falciparum CS repeat region and elicited antisporozoite Ab responses in all of the MAP-immunized mice. Synthetic
peptide malaria vaccines containing the aa 326-345 universal
T cell epitope would be expected to elicit parasite-specific immune responses in both sporozoite-primed and naive individuals of diverse genetic backgrounds.