Abstract
Background: RTS,S/AS01 E, the most advanced malaria vaccine confers partial immunity. The vaccine-induced pre-erythrocytic immunity reduces exposure to blood-stage parasites, delaying acquisition of antibodies to blood-stage antigens. However, the duration of this effect is unknown. Methods: We measured, by enzyme-linked immunosorbent assay, IgG-antibodies to 4 Plasmodium falciparum blood-stage antigens (AMA1, MSP1 42, EBA175, and MSP3) on 314 children randomized to receive RTS,S/AS01 E or Rabies vaccine at 5 - 17 months of age in a phase 2b trial in Kenya, and thereafter participated in a 7-year study of the duration of vaccine immunity. Results: Antibody levels to MSP1 42, AMA1 and EBA175 were slightly lower among the RTS,S/AS01 E recipients, relative to the Rabies-control vaccinees, during the first 48 months of surveillance. Irrespective of vaccine arm, antibody levels to merozoite antigens were positively associated with the risk for malaria. However, this was only apparent at high levels for EBA175 and AMA1 and was not evident after adjusting for heterogeneity in malaria-exposure. Among children with asymptomatic parasitaemia, antibody levels were associated with reduced clinical malaria. Conclusions: The reduction in levels of antibodies to blood-stage antigens induced by vaccination with RTS,S/AS01 E can last for several years. In absence of asymptomatic infection, anti-merozoite antibody levels were unreliable correlates of clinical immunity.
Highlights
Despite the recent gains in malaria control, the disease remains a major public health risk, with 216 million cases and 445,000 deaths associated with malaria in 20161
Antibody levels for AMA1, EBA175 and MSP1 diverged after vaccination, with levels being higher among the Rabies control vaccinees than the RTS,S/AS01 vacE
The divergence was temporal for AMA1 and EBA175, as the differences in the median antibody levels reduced with time and were similar by 48 months of the third dose of vaccination
Summary
Despite the recent gains in malaria control, the disease remains a major public health risk, with 216 million cases and 445,000 deaths associated with malaria in 20161. The vaccine-induced pre-erythrocytic immunity reduces exposure to blood-stage parasites, delaying acquisition of antibodies to blood-stage antigens. Methods: We measured, by enzyme-linked immunosorbent assay, IgG-antibodies to 4 Plasmodium falciparum blood-stage antigens (AMA1, MSP142, EBA175, and MSP3) on 314 children randomized to receive RTS,S/AS01 E or Rabies vaccine at 5 – 17 months of age in a phase 2b trial in Kenya, and thereafter participated in a 7-year study of the duration of vaccine immunity. Irrespective of vaccine arm, antibody levels to merozoite antigens were positively associated with the risk for malaria. This was only apparent at high levels for EBA175 and AMA1 and was not evident after adjusting for heterogeneity in malaria-exposure. In absence of asymptomatic infection, anti-merozoite antibody levels were unreliable correlates of clinical immunity
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