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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
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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.
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WHITE, Michael t., VERITY, Robert, GRIFFIN, Jamie t., ASANTE, Kwaku poku, OWUSU-AGYEI, Seth, GREENWOOD, Brian, DRAKELEY, Chris, GESASE, Samwel, LUSINGU, John, ANSONG, Daniel, ADJEI, Samuel, AGBENYEGA, Tsiri, OGUTU, Bernhards, OTIENO, Lucas, OTIENO, Walter, AGNANDJI, Selidji todagbe, LELL, Bertrand, KREMSNER, Peter g., HOFFMAN, Irving, MARTINSON, Francis, KAMTHUNZI, Portia, TINTO, Halidou, VALÉA, Innocent, SORGHO, Hermann, ONEKO, Martina, OTIENO, Kephas, HAMEL, Mary j., SALIM, Nahya, MTORO, Ali takadir, ABDULLA, Salim, AIDE, Pedro carlos paulino, SACARLAL, Jahit, APONTE, John j., NJUGUNA, Patricia, MARSH, Kevin, BEJON, Philip, RILEY, Eleanor m., GHANI, Azra c.. 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. _The Lancet. Infectious Diseases_. 2015. Vol. 15, núm. 12, pàgs. 1450-1458. [consulta: 23 de gener de 2026]. ISSN: 1473-3099. [Disponible a: https://hdl.handle.net/2445/69263]