ehealth digital library

Digital library of
the Tanzania

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., Asante, K. P., Owusu-Agyei, S., Greenwood, B., Drakeley, C., Gesase, S., Lusingu, J., 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., Hamel, 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. The Lancet. Infectious diseases. ISSN 1474-4457

Michael_T_White.pdf - Published Version
Available under License Creative Commons Attribution Non-commercial.

Download (591kB)


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. 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. 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. 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.

Item Type: Article
Keywords: Immunogenicity, RTS,S/AS01, Malaria Vaccine, Plasmodium Falciparum Infection
Subjects: Malaria > Vaccines
Divisions: Ifakara Health Institute > Biomedical
Depositing User: Mr Joseph Madata
Date Deposited: 27 Jun 2016 05:48
Last Modified: 27 Jun 2016 05:48

Actions (login required)

Edit Item Edit Item


Downloads per month over past year

View more statistics