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Title: 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
Author: 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.
Keywords: Vacuna de la malària
Plasmodium falciparum
Assaigs clínics
Malaria vaccine
Plasmodium falciparum
Clinical trials
Issue Date: 2-Sep-2015
Publisher: Elsevier Ltd.
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 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.
Note: Reproducció del document publicat a:
It is part of: The Lancet. Infectious Diseases, 2015, vol. 15, num. 12, p. 1450-1458
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ISSN: 1473-3099
Appears in Collections:Articles publicats en revistes (ISGlobal)

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