RTS,S/AS02A/1B induces antibodies to a novel Plasmodium falciparum circumsporozoite protein epitope with sequence similarities to the junctional region

Abstract

Background: Plasmodium falciparum circumsporozoite protein (CSP) is the target of multiple vaccines in development. New promising monoclonal antibodies target the CSP junctional region, which is not contained in the RTS,S vaccine. Methods: We compared CSP antibody responses on a diversity-reflecting peptide array between adults receiving a full-length CSP (rCSP) vaccine and unprotected after controlled human malaria infection (CHMI), adults receiving RTS,S and protected after CHMI, and adults receiving RTS,S and unprotected after CHMI. Results: Overall, the rCSP group had lower anti-CSP antibody responses compared to the RTS,S-protected group. An epitope of interest in the C-terminal region was identified for both RTS,S groups that had sequence similarities to junctional region epitopes, and the RTS,S-protected group responded to more diverse peptides at this epitope than the RTS,S-unprotected group. Conclusions: Sequence similarities between the identified C-terminal epitope and junctional region epitopes warrant further investigation into whether these are cross-reactive antibodies driving protective responses.