BibTex format
@article{White:2014:10.1186/s12916-014-0117-2,
author = {White, MT and Bejon, P and Olotu, A and Griffin, JT and Bojang, K and Lusingu, J and Salim, N and Abdulla, S and Otsyula, N and Agnandji, ST and Lell, B and Asante, KP and Owusu-Agyei, S and Mahama, E and Agbenyega, T and Ansong, D and Sacarlal, J and Aponte, JJ and Ghani, AC},
doi = {10.1186/s12916-014-0117-2},
journal = {BMC Medicine},
title = {A combined analysis of immunogenicity, antibody kinetics and vaccine efficacy from phase 2 trials of the RTS,S malaria vaccine},
url = {http://dx.doi.org/10.1186/s12916-014-0117-2},
volume = {12},
year = {2014}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Background: The RTS,S malaria vaccine is currently undergoing phase 3 trials. High vaccine-induced antibody titresto the circumsporozoite protein (CSP) antigen have been associated with protection from infection and episodes ofclinical 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 <0.001),pre-vaccination anti-hepatitis B surface antigen titres (P = 0.005) and pre-vaccination anti-CSP titres (P <0.001).Co-administration with other vaccines reduced anti-CSP antibody titres although not significantly (P = 0.095).Antibody titres showed a bi-phasic decay over time with an initial rapid decay in the first three months and asecond slower decay over the next three to four years. Antibody titres were significantly associated with protection,with a titre of 51 (95% Credible Interval (CrI): 29 to 85) ELISA units/ml (EU/mL) predicted to prevent 50% of infections inchildren. Vaccine efficacy was predicted to decline to zero over four years in a setting with entomological inoculationrate (EIR) = 20 infectious bites per year (ibpy). Over a five-year follow-up period at an EIR = 20 ibpy, we predict RTS,S willavert 1,782 cases per 1,000 vaccinated children, 1,452 cases per 1,000 vaccinated infants, and 887 cases per 1,000 infantswhen co-administered with expanded programme on immunisation (EPI) vaccines. Our main study limitations includean absence of vaccine-induced cellular immune responses and short duration of follow-up in some individuals.Conclusions: Vaccine-induced anti-CSP antibody titres and transmission intensity can explain variations in observedva
AU - White,MT
AU - Bejon,P
AU - Olotu,A
AU - Griffin,JT
AU - Bojang,K
AU - Lusingu,J
AU - Salim,N
AU - Abdulla,S
AU - Otsyula,N
AU - Agnandji,ST
AU - Lell,B
AU - Asante,KP
AU - Owusu-Agyei,S
AU - Mahama,E
AU - Agbenyega,T
AU - Ansong,D
AU - Sacarlal,J
AU - Aponte,JJ
AU - Ghani,AC
DO - 10.1186/s12916-014-0117-2
PY - 2014///
SN - 1741-7015
TI - A combined analysis of immunogenicity, antibody kinetics and vaccine efficacy from phase 2 trials of the RTS,S malaria vaccine
T2 - BMC Medicine
UR - http://dx.doi.org/10.1186/s12916-014-0117-2
UR - http://hdl.handle.net/10044/1/28331
VL - 12
ER -