NATURAL ANTIBODY-RESPONSES AGAINST THE NON-REPEAT-SEQUENCE-BASED B-CELL EPITOPES OF THE PLASMODIUM-FALCIPARUM CIRCUMSPOROZOITE PROTEIN

Synthetic peptides and human serum or plasma samples from regions of B razil, Papua New Guinea, and Kenya in which malaria is endemic were us ed to identify B-cell epitopes localized outside the repeat region of the circumsporozoite (CS) protein of the human malaria parasite Plasmo dium falciparum. In agreement with recent observations, our results co nfirm the presence of two non-repeat-region-based B-cell epitopes of t he CS protein. Of these two epitopes, only the region I epitope (KPKHK KLKQPGDGNP) was previously shown to be recognized by human sera. In th is study, we show that human immune sera from malarious regions recogn ize another B-cell epitope, ENANANNAV, that resides carboxyl to the re peat region. The present study reveals that (i) the repeat-sequence (N ANP)-based B-cell epitope of the CS protein is an immunogenic but not immunodominant epitope; (ii) the natural expression of antibody respon ses to the two non-repeat-region-based B-cell epitopes of the CS prote in varies in different populations in which malaria is endemic; (iii) although the host immune responses to the non-repeat-region-based B-ce ll epitopes increase as a function of host age, this increase is not s tatistically significant for the region I epitope but is significant f or the other epitope; and (iv) the Th1R T-cell site but not the Th2R o r Th3R T-cell site induces an antibody response in the human host. Thi s study confirms the immunogenic potential of non-repeat-region-based B-cell epitopes and suggests that antibody pressures may also contribu te to the maintenance of the antigenic diversity of the CS protein.