Antibodies targeting blood stage antigens of Plasmodium falciparum are associated with resistance to malaria infection and disease

BACKGROUND: Current licensed malaria vaccines are modestly protective against severe Plasmodium falciparum malaria but do not contain components which control blood stage infection. We evaluated the impact of antibodies to three blood stage candidate antigens (PfGARP, PfSEA-1, and PfGBP130) on P. falciparum infection and disease in a longitudinal cohort of children living in a holoendemic region of Western Kenya. METHODS: We enrolled and followed 266 children aged 2 to 7 years living in Western Kenya. Over the course of a 3-year follow-up period, we actively assessed their health status weekly, collected blood samples monthly to assess P. falciparum infection incidence and intensity, and measure IgG antibody levels to blood stage vaccine candidate antigens. RESULTS: Children with high levels of IgG antibodies to PfGBP130 or PfGARP, but not PfSEA-1, experienced 3.4- and 1.9- fold lower parasite densities respectively compared to those with low antibody levels (both P < 0.002). In addition, children with high levels of both anti-PfGBP130 and anti-PfGARP had significantly lower risk of clinical malaria compared to children with low antibody levels (HR: 0.58, 95% CI: 0.85-0.40). Over the 3-year follow-up period, individuals with elevated anti-PfGBP130 and anti-PfGARP antibody levels experienced an average of 4.51 cases of clinical malaria while those with lower levels experienced an average of 7.11 cases of clinical malaria (P = 0.005). CONCLUSIONS: Higher antibody levels to PfGBP130 and PfGARP predict significantly lower parasite densities and lower risks of clinical malaria among 2- to 7-year-old children residing in a holoendemic area of Kenya.