Autor/a:
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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; Kamthunzu, Portia; Tinto, Halidou; Valéa, Innocent; Sorgho, Hermann; Oneko, Martina; Otieno, Kephas; Hamel, Mary J.; Salim, Nahya; Mtoro, Ali; Abdulla, Salim; Aide, Pedro Carlos Paulino; Sacarlal, Jahit; Aponte, John J.; Njuguna, Patricia; Marsh, Kevin; Bejon, Philip; Riley, Eleanor M.; Ghani, Azra C.
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Abstract:
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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. |