Peptide vaccines containing minimal
epitopes of protective Ags provide the advantages of low cost, safety, and stability while focusing host responses on relevant targets of protective immunity. However, the limited complexity of
malaria peptide vaccines raises questions regarding their equivalence to immune responses elicited by the irradiated sporozoite
vaccine, the "gold standard" for protective immunity. A panel of CD4+ T cell clones was derived from volunteers immunized with a
peptide vaccine containing minimal T and
B cell epitopes of the Plasmodium falciparum circumsporozoite
protein to compare these with previously defined CD4+ T cell clones from volunteers immunized with irradiated P. falciparum sporozoites. As found following sporozoite immunization, the majority of clones from the
peptide-immunized volunteers recognized the T*
epitope, a predicted universal
T cell epitope, in the context of multiple
HLA DR and DQ molecules.
Peptide-induced T cell clones were of the Th0 subset, secreting high levels of IFN-gamma as well as variable levels of Th2-type
cytokines (IL-4, IL-6). The T*
epitope overlaps a polymorphic region of the circumsporozoite
protein and strain cross-reactivity of the
peptide-induced clones correlated with recognition of core
epitopes overlapping the conserved regions of the T*
epitope. Importantly, as found following sporozoite immunization, long-lived CD4+ memory cells specific for the T*
epitope were detectable 10 mo after
peptide immunization. These studies demonstrate that
malaria peptides containing minimal
epitopes can elicit human CD4+ T cells with fine specificity and potential effector function comparable to those elicited by attenuated P. falciparum sporozoites.