ABSTRACT
The march of drug-resistant parasite strains [1], the spread of insecticideresistant mosquito vectors [2], and the recognition that global morbidity and mortality due to malaria equals that of HIV/AIDS [3] have made malaria vaccine development a global imperative [4]. In broad terms, there are three possible goals for a malaria vaccine. Each goal requires a specific vaccine development strategy targeted against specific parasite stages. A malaria vaccine intended to confer sterile immunity would target pre-erythrocytic stages of the malaria parasite, i.e., the sporozoite, liver stages, or hepatic merozoites prior to initial red cell invasion. A vaccine designed to prevent severe disease or death, but not necessarily preventing parasitemia, should aim immune responses against asexual blood stages or toxins. Lastly, a vaccine designed to prevent transmission of malaria from host to vector to host would direct immune responses against sexual stage antigens present in either the host or the mosquito vector. A long-term goal of researchers in this field has been to develop and license a multistage, multiantigen vaccine against Plasmodium falciparum that protects malaria-naïve children and adults against infection, limits morbidity in those who develop infection, and is effective for at least 12 months. This goal may require the inclusion of multiple parasite antigens including antigens from more than one stage of the parasite’s life cycle. Since the mid 1980s, our efforts have focused upon the development of a safe, well-tolerated, and effective pre-erythrocytic vaccine. This chapter emphasizes recent progress in our co-development with GlaxoSmithKline Biologicals of the sporozoite-based RTS, S/AS02A vaccine and reviews
other protein-based pre-erythrocytic malaria vaccines currently in clinical development.
