Immunogenicity of the RTS,S/AS01 malaria vaccine and implications for duration of vaccine efficacy: secondary analysis of data from a phase 3 randomised controlled trial  Dr Michael T White, PhD, Robert Verity, PhD, Jamie T Griffin, PhD, Kwaku Poku Asante, MD, Seth Owusu-Agyei, PhD, Prof Brian Greenwood, MD, Prof Chris Drakeley, PhD, Samwel Gesase, MD, John Lusingu, MD, Daniel Ansong, MBChB, Samuel Adjei, MBChB, Tsiri Agbenyega, PhD, Bernhards Ogutu, MD, Lucas Otieno, MD, Walter Otieno, MD, Selidji T Agnandji, MD, Bertrand Lell, MD, Prof Peter Kremsner, MD, Prof Irving Hoffman, MPH, Francis Martinson, PhD, Portia Kamthunzu, MD, Halidou Tinto, PhD, Innocent Valea, PhD, Hermann Sorgho, PhD, Martina Oneko, MD, Kephas Otieno, MD, Mary J Hamel, MD, Nahya Salim, PhD, Ali Mtoro, MD, Salim Abdulla, MD, Pedro Aide, PhD, Jahit Sacarlal, PhD, John J Aponte, PhD, Patricia Njuguna, MMed, Prof Kevin Marsh, MD, Prof Philip Bejon, PhD, Prof Eleanor M Riley, PhD, Prof Azra C Ghani, PhD  The Lancet Infectious Diseases  Volume 15, Issue 12, Pages 1450-1458 (December 2015) DOI: 10.1016/S1473-3099(15)00239-X Copyright © 2015 White et al. Open Access article distributed under the terms of CC BY Terms and Conditions

Figure 1 Anti-circumsporozoite antibody dynamics and association with efficacy against infection (A–D) Anti-circumsporozoite antibody dynamics after a primary schedule of RTS,S/AS01 with or without booster. The black bars denote the median and 95% ranges (2·5–97·5 percentile). The solid and dashed curves denote the median of the model predicted antibody titres. The dark and light shaded regions represent 50% and 95% of the model predicted variation in antibody titres. (E) Estimated dose–response relationship for the association between anti-CS antibody titre and efficacy against infection. (F) Estimated vaccine efficacy profile for infection based on waning antibody titres. CS=circumsporozoite. R3C=three doses of RTS,S/AS01 and a booster with a comparator vaccine. R3R=three doses of RTS,S/AS01 and a booster with RTS,S/AS01. The Lancet Infectious Diseases 2015 15, 1450-1458DOI: (10.1016/S1473-3099(15)00239-X) Copyright © 2015 White et al. Open Access article distributed under the terms of CC BY Terms and Conditions

Figure 2 Vaccine efficacy profile for clinical malaria in children aged 6–12 weeks Data are point estimates of efficacy with 95% CIs, presented in 6 month and 3 month windows in low and high transmission sites, respectively. Kilifi, Korogwe, Bagamoyo, Lambarene, Manhica, and Lilongwe are low transmission sites. Agogo, Kombewa, Kintampo, Siaya, and Nanoro are high transmission sites. Cases of malaria are based on the primary case definition in the per-protocol population from 2·5 months to study end. The posterior median estimates of efficacy against clinical malaria predicted by the antibody dynamics model are presented in red. R3C=three doses of RTS,S/AS01 and a booster with a comparator vaccine. R3R=three doses of RTS,S/AS01 and a booster with RTS,S/AS01. The Lancet Infectious Diseases 2015 15, 1450-1458DOI: (10.1016/S1473-3099(15)00239-X) Copyright © 2015 White et al. Open Access article distributed under the terms of CC BY Terms and Conditions

Figure 3 Vaccine efficacy profile for clinical malaria in children aged 5–17 months Data are point estimates of efficacy with 95% CIs, presented in 6 month and 3 month windows in low and high transmission sites, respectively. Kilifi, Korogwe, Bagamoyo, Lambarene, and Lilongwe are low transmission sites. Agogo, Kombewa, Kintampo, Siaya, and Nanoro are high transmission sites. There were no data for infants aged 5–17 months Manhica in the per-protocol cohort. Cases of malaria are based on the primary case definition in the per-protocol population from 2·5 months to study end. The posterior median estimates of efficacy against clinical malaria predicted by the antibody dynamics model are presented in red. R3C=three doses of RTS,S/AS01 and a booster with a comparator vaccine. R3R=three doses of RTS,S/AS01 and a booster with RTS,S/AS01. The Lancet Infectious Diseases 2015 15, 1450-1458DOI: (10.1016/S1473-3099(15)00239-X) Copyright © 2015 White et al. Open Access article distributed under the terms of CC BY Terms and Conditions