Malaria has a tremendous impact on human health, killing millions annually and the disease is a major impediment for social and economic development of nations in malaria-endemic areas, particularly in sub-Saharan Africa (Sachs & Malaney (2002) Nature 415:680-85). Malaria is a mosquito-borne disease that is transmitted by inoculation of the Plasmodium parasite sporozoite stage. Sporozoites invade hepatocytes (Kappe et al. (2003) Trends Parasitol. 19:135-43), transform into liver stages, and subsequent liver stage development ultimately results in release of pathogenic merozoites that initiate the blood stage cycle of infection (Shortt & Garnham (1948) Nature 161:126).
Protection against blood stage malaria can be passively transferred by antibodies. Effectiveness of passive transfer of IgG between adults and children living in different geographic regions indicate that the antigens that are targeted by antibodies that protect against blood stage malaria are conserved (see Duffy et al. (2005) Vaccine 23 (17-18):2235-42). The best evidence that naturally occurring immunity against blood stage malaria targets the IRBC surface comes from studies of pregnancy malaria. In areas of stable malaria transmission, adults enjoy immunity that limits parasitemia and prevents disease. Women become more susceptible during pregnancy, and previously this was ascribed to pregnancy-related immunomodulation that develops to prevent rejection of the fetal allograft. However, susceptibility is greatest in primigravid women and diminishes over successive pregnancies, suggesting an acquired immune response to an antigenically distinct microbe. Placental isolates of P. falciparum commonly bind to chondroitin sulfate A (CSA) expressed on the surface of the syncytiotrophoblast (the cells lining the maternal vascular space in the placenta), and this phenotype is uncommon among isolates obtained from non-pregnant individuals (Fried & Duffy (1996) Science 272:1502-4). The distinct binding phenotype renders pregnant women naïve to this parasite population during their first pregnancy (primigravidas). Women with multiple pregnancies (multigravidas) residing in areas of stable malaria transmission develop antibodies that inhibit parasite adhesion to CSA (Fried et al. (1998) Nature 395:851-2). These anti-adhesion antibodies are associated with a reduced mass of parasites in the placenta, and substantial improvements in fetal development (Duffy & Fried (2003) Infect. Immun. 71:6620-3). Because CSA-binding parasites cross-react with sera donated by mothers throughout Asia and Africa, the antigen targeted by protective antibodies is presumed to have conserved features or limited diversity.
There is a need in the art for vaccines that protect against malaria infection and disease. There is also a need in the art for diagnostic markers for malaria. The present invention addresses these needs and others.