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, MT; Verity, R; Griffin, JT; Asante, KP; Owusu-Agyei, S; Greenwood, B; Drakeley, C; Gesase, S; Lusingu, J; Ansong, D; Adjei, S; Agbenyega, T; Ogutu, B; Otieno, L; Otieno, W; Agnandji, ST; Lell, B; Kremsner, P; Hoffman, I; Martinson, F; Kamthunzu, P; Tinto, H; Valea, I; Sorgho, H; Oneko, M; Otieno, K; Hamel, MJ; Salim, N; Mtoro, A; Abdulla, S; Aide, P; Sacarlal, J; Aponte, JJ; Njuguna, P; Marsh, K; Bejon, P; Riley, EM; Ghani, AC; (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, 15 (12). pp. 1450-1458. ISSN 1473-3099 DOI: 10.1016/s1473-3099(15)00239-x

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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.

Item Type: Article
Keywords: PLASMODIUM-FALCIPARUM INFECTION, PREERYTHROCYTIC IMMUNITY, AFRICAN, CHILDREN, HUMORAL IMMUNITY, PROTECTION, ANTIBODY, IMMUNIZATION, MECHANISMS, EXPOSURE, INFANTS
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Disease Control
Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Malaria Centre
Vaccine Centre
PubMed ID: 26342424
Web of Science ID: 365144800031
URI: http://researchonline.lshtm.ac.uk/id/eprint/2531030

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