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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

White, M. T., Verity, R., Griffin, J. T., Greenwood, B., Drakeley, C., Ansong, D., Adjei, S., Agbenyega, T., Ogutu, B., Otieno, L., Otieno, W., Agnandji, S. T., Lell, B., Kremsner, P., Hoffman, I., Martinson, F., Kamthunzu, P., Tinto, H., Valea, I., Sorgho, H., Oneko, M., Otieno, K., Hame, M. J., Salim, N., Mtoro, A., Abdulla, S., Aide, P., Sacarlal,, J., Aponte, J. J., Njuguna, P., Marsh, K., Bejon, P., Riley, E. M. and Ghani, A. C. (2015) 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. Lancet Infectious Diseases. ISSN 1473-3099

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Abstract

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. Using data from 8922 African children aged 5 1317 months and 6537 African infants aged 6 1312 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. RTS,S/AS01-induced anti-circumsporozoite antibody titres were greater in children aged 5 1317 months than in those aged 6 1312 weeks. Pre-vaccination anti-circumsporozoite titres were associated with lower immunogenicity in children aged 6 1312 weeks and higher immunogenicity in those aged 5 1317 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 1317 months, the half-life of the shortlived component of the antibody response was 45 days (95% credible interval 42 1348) and that of the long-lived component was 591 days (557 13632). After primary vaccination 12% (11 1313) of the response was estimated to be longlived, rising to 30% (28 1332%) after a booster dose. An anti-circumsporozoite antibody titre of 121 EU/mL (98 13153) 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 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.

Item Type: Article
Keywords: RTS,S/AS01, Malaria, Vaccine, Plasmodium falciparum, Immunization
Subjects: Malaria > Vaccines
Divisions: Ifakara Health Institute > Biomedical
Depositing User: Mr Joseph Madata
Date Deposited: 09 Sep 2015 06:18
Last Modified: 09 Sep 2015 06:18
URI: http://ihi.eprints.org/id/eprint/3342

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