Open Peer Review Any reports and responses or comments on the article can be found at the end of the article. RESEARCH ARTICLE A seven-year study on the effect of the pre-erythrocytic malaria vaccine candidate RTS,S/AS01 on blood stage immunity in young Kenyan children [version 1; referees: awaiting peer review] Francis M. Ndungu , Jedida Mwacharo , Juliana Wambua , Patricia Njuguna , Kevin Marsh , Chris Drakeley , Philip Bejon 2 Department of Biosciences, KEMRI/Wellcome Trust Research Programme, Kilifi, 80108, Kenya Infection & Immunity Department, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK Abstract : RTS,S/AS01 , the most advanced malaria vaccine confers Background 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. We measured, by enzyme-linked immunosorbent assay, Methods: IgG-antibodies to 4 blood-stage antigens (AMA1, Plasmodium falciparum MSP1 , EBA175, and MSP3) on 314 children randomized to receive RTS,S/AS01 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. : Antibody levels to MSP1 , AMA1 and EBA175 were slightly lower Results among the RTS,S/AS01 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. : The reduction in levels of antibodies to blood-stage antigens Conclusions induced by vaccination with RTS,S/AS01 can last for several years. In absence of asymptomatic infection, anti-merozoite antibody levels were unreliable correlates of clinical immunity. Keywords Plasmodium falciparum, malaria, RTS, S/AS01 E, Vaccines, immunity, pre-erythrocytic, blood stages E 1 1 1 1 1 2 2 1 2 Referee Status: AWAITING PEER REVIEW 05 Mar 2019, :42 ( First published: 4 ) https://doi.org/10.12688/wellcomeopenres.15002.1 05 Mar 2019, :42 ( Latest published: 4 ) https://doi.org/10.12688/wellcomeopenres.15002.1 v1 E 42 E 42 E E Page 1 of 8 Wellcome Open Research 2019, 4:42 Last updated: 05 MAR 2019