Peptide immunization can elicit malaria protein-specific memory helper but not proliferative T cells

We have studied the proliferative and helper T cell responses in mice to a malaria sporozoite vaccine candidate currently undergoing human trials. Following immunization of B10 (I-Ab) mice with the purified recombinant baculovirus-expressed Plasmodium falciparum circumsporozoite protein, draining lymph node cells were challenged in vitro with a series of overlapping synthetic peptides which span the construct. Surprisingly, only a single peptide from the protein was immunodominant in that it could reproducibly elicit a significant proliferative response from the immunized lymph node cells. This epitope, (NANP)n, is also the repetitive immunodominant B cell epitope of the protein. However, immunization of mice with synthetic peptides revealed at least 3 cryptic proliferative epitopes--epitopes not revealed by protein immunization--two of which represent conserved regions of the protein. While cryptic peptide-immunization did not elicit protein-specific proliferative T cells, it did reveal protein-specific helper T cells, as shown by an in vivo assay. Identification of "cryptic" epitopes not only for malaria but for other infectious diseases may aid vaccine design, especially in situations where subunit vaccines are sought.