White et al. BMC Medicine 2014, 12:117 http://www.biomedcentral.com/1741-7015/12/117
Medicine for Global Health
RESEARCH ARTICLE
Open Access
A combined analysis of immunogenicity, antibody kinetics and vaccine efficacy from phase 2 trials of the RTS,S malaria vaccine Michael T White1*, Philip Bejon2,3, Ally Olotu2, Jamie T Griffin1, Kalifa Bojang4, John Lusingu5, Nahya Salim6, Salim Abdulla6, Nekoye Otsyula7, Selidji T Agnandji8,9, Bertrand Lell8,9, Kwaku Poku Asante10, Seth Owusu-Agyei10, Emmanuel Mahama10, Tsiri Agbenyega11, Daniel Ansong11, Jahit Sacarlal12,13, John J Aponte12,14 and Azra C Ghani1
Abstract Background: The RTS,S malaria vaccine is currently undergoing phase 3 trials. High vaccine-induced antibody titres to the circumsporozoite protein (CSP) antigen have been associated with protection from infection and episodes of clinical malaria. Methods: Using data from 5,144 participants in nine phase 2 trials, we explore predictors of vaccine immunogenicity (anti-CSP antibody titres), decay in antibody titres, and the association between antibody titres and clinical outcomes. We use empirically-observed relationships between these factors to predict vaccine efficacy in a range of scenarios. Results: Vaccine-induced anti-CSP antibody titres were significantly associated with age (P = 0.04), adjuvant (P 3 months and
Medicine for Global Health
RESEARCH ARTICLE
Open Access
A combined analysis of immunogenicity, antibody kinetics and vaccine efficacy from phase 2 trials of the RTS,S malaria vaccine Michael T White1*, Philip Bejon2,3, Ally Olotu2, Jamie T Griffin1, Kalifa Bojang4, John Lusingu5, Nahya Salim6, Salim Abdulla6, Nekoye Otsyula7, Selidji T Agnandji8,9, Bertrand Lell8,9, Kwaku Poku Asante10, Seth Owusu-Agyei10, Emmanuel Mahama10, Tsiri Agbenyega11, Daniel Ansong11, Jahit Sacarlal12,13, John J Aponte12,14 and Azra C Ghani1
Abstract Background: The RTS,S malaria vaccine is currently undergoing phase 3 trials. High vaccine-induced antibody titres to the circumsporozoite protein (CSP) antigen have been associated with protection from infection and episodes of clinical malaria. Methods: Using data from 5,144 participants in nine phase 2 trials, we explore predictors of vaccine immunogenicity (anti-CSP antibody titres), decay in antibody titres, and the association between antibody titres and clinical outcomes. We use empirically-observed relationships between these factors to predict vaccine efficacy in a range of scenarios. Results: Vaccine-induced anti-CSP antibody titres were significantly associated with age (P = 0.04), adjuvant (P 3 months and
