RTS,S: the first malaria vaccine
Fidel Zavala
Abstract
After more than four decades of basic research and clinical trials, the World Health Organization (WHO) has recommended the malaria vaccine RTS,S for widespread use among children living in malaria endemic areas. Pioneering studies using rodent malaria models directed by Ruth S. Nussenzweig at the New York University School of Medicine demonstrated in the late 1960s that immunization with attenuated sporozoites -the infective stage of Plasmodium -induces immune responses that protect against parasite infection (1). These studies also identified the circumsporozoite protein (CSP), the sporozoite-specific molecule recognized by the protective immune responses that is the antigen incorporated in the RTS,S vaccine (2). The CSP is expressed on the surface of sporozoites of different Plasmodium species and contains a central domain of tandem repeats that represent approximately 30% of the entire sequence. Extensive experimental evidence indicates that binding of antibodies to these repeats immobilizes the sporozoites, preventing infection of hepatocytes, an obligatory stage of this infection (Figure The RTS,S vaccine is a hepatitis B virus-like particle that contains a genetically fused portion of the repeat domain and the C-terminal region of the P. falciparum CSP (3).