# name
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

# metadata.dc.description.abstract[].value
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 efficacy 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 first 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 short-lived
                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 long-lived, 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 efficacy against clinical malaria across different
                age categories and transmission intensities, and efficacy 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
                efficacy, with or without a booster dose, providing a valuable
                surrogate of effectiveness for new RTS,S formulations in the age
                groups considered. FUNDING: UK Medical Research Council.

# metadata.dc.source[].value
Articles publicats en revistes (ISGlobal)

# metadata.dc.title[].value
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