Circumsporozoite protein as a potential target for antimalarials

Since the discovery of circumsporozoite protein (CSP), a major sporozoite surface antigen, by Ruth Nussenzweig and Victor Nussenzweig in the early 1980s, the role of CSP in protection against malaria has been extensively investigated. Several monoclonal antibodies against CSP have been generated to date, with some of them mediating antimalarial protection upon passive transfer into animals. Genetically engineered transgenic mosquitoes producing the anti-CSP antibody have recently been generated to reduce malarial transmission. A monoclonal anti-CSP antibody was produced in mice by adeno-associated virus vector, which protected them from malaria. Phase III trials with RTS, S vaccine that targets CSP of Plasmodium falciparum have shown modest efficacy. Polyclonal anti-CSP antibodies derived from children who received the RTS, S vaccine failed to block malarial transmission through mosquitoes, but passive transfer of monoclonal antibodies raised from RTS, S-vaccinated recipient conferred protection against malaria in mice. Taken together, these findings may imply CSP as an antimalarial target.