dc.contributor.author | Michael T White, Robert Verity, Jamie T Griffin, Kwaku Poku Asante, Seth Owusu-Agyei, Brian Greenwood, Chris Drakeley, Samwel Gesase, John Lusingu, Daniel Ansong, Samuel Adjei, Tsiri Agbenyega, Bernhards Ogutu, Lucas Otieno, Walter Otieno, Selidji T Agnandji, Bertrand Lell, Peter Kremsner, Irving Hoffman, Francis Martinson, Portia Kamthunzu, Halidou Tinto, Innocent Valea, Hermann Sorgho, Martina Oneko, Kephas Otieno, Mary J Hamel, Nahya Salim, Ali Mtoro, Salim Abdulla, Pedro Aide, Jahit Sacarlal, John J Aponte, Patricia Njuguna, Kevin Marsh, Philip Bejon, Eleanor M Riley, Azra C Ghani | |
dc.description.abstract | Background The RTS,S/AS01 malaria vaccine targets the circumsporozoite protein, inducing antibodies associated
with the prevention of Plasmodium falciparum infection. We assessed the association between anti-circumsporozoite
antibody titres and the magnitude and duration of vaccine effi cacy using data from a phase 3 trial done between 2009
and 2014.
Methods Using data from 8922 African children aged 5–17 months and 6537 African infants aged 6–12 weeks at fi rst
vaccination, we analysed the determinants of immunogenicity after RTS,S/AS01 vaccination with or without a
booster dose. We assessed the association between the incidence of clinical malaria and anti-circumsporozoite
antibody titres using a model of anti-circumsporozoite antibody dynamics and the natural acquisition of protective
immunity over time.
Findings RTS,S/AS01-induced anti-circumsporozoite antibody titres were greater in children aged 5–17 months than
in those aged 6–12 weeks. Pre-vaccination anti-circumsporozoite titres were associated with lower immunogenicity in
children aged 6–12 weeks and higher immunogenicity in those aged 5–17 months. The immunogenicity of the
booster dose was strongly associated with immunogenicity after primary vaccination. Anti-circumsporozoite titres
wane according to a biphasic exponential distribution. In participants aged 5–17 months, the half-life of the shortlived component of the antibody response was 45 days (95% credible interval 42–48) and that of the long-lived
component was 591 days (557–632). After primary vaccination 12% (11–13) of the response was estimated to be longlived, rising to 30% (28–32%) after a booster dose. An anti-circumsporozoite antibody titre of 121 EU/mL (98–153) was
estimated to prevent 50% of infections. Waning anti-circumsporozoite antibody titres predict the duration of effi cacy
against clinical malaria across diff erent age categories and transmission intensities, and effi cacy wanes more rapidly
at higher transmission intensity.
Interpretation Anti-circumsporozoite antibody titres are a surrogate of protection for the magnitude and duration of
RTS,S/AS01 effi cacy, with or without a booster dose, providing a valuable surrogate of eff ectiveness for new RTS,S
formulations in the age groups considered. | en_US |