A combined analysis of immunogenicity, antibody kinetics and vaccine efficacy from phase 2 trials of the RTS,S malaria vaccine

BMC Medicine

Azra C Ghani⁷  John J Aponte⁹  Jahit Sacarlal⁵  Daniel Ansong^1,11  Tsiri Agbenyega^1,11  Emmanuel Mahama¹  Seth Owusu-Agyei¹  Kwaku Poku Asante¹  Bertrand Lell⁴  Selidji T Agnandji⁴  Nekoye Otsyula^1,12  Salim Abdulla³  Nahya Salim³  John Lusingu⁶  Kalifa Bojang^1,10  Jamie T Griffin⁷  Ally Olotu²  Philip Bejon⁸  Michael T White⁷ 

[1] Kintampo Health Research Centre, Kintampo, Ghana;KEMRI-Wellcome Trust Research Programme, Kenya Medical Research Institute, Kilifi, Kenya;Ifakara Health Institute, Bagamoyo, Tanzania;Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany;Faculdade de Medicina, Universidade Eduardo Mondlane, Avenida do Zimbabwe, Maputo, Mozambique;National Institute for Medical Research, Tanga Centre, Tanga, Tanzania;MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London W2 1PG, UK;Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, UK;Barcelona Centre for International Health Research (CRESIB), Universitat de Barcelona, Barcelona, Spain;Medical Research Council Unit, Fajara, The Gambia;School of Medical Sciences, Kumasi, Ghana;Kenya Medical Research Institute, and US Army Medical Research Unit–Kenya, Nairobi, Kenya

关键词: Clinical immunity;    Mathematical model;    Phase 2 clinical trials;    RTS,S;    Antibody;    Circumsporozoite protein;    Vaccine;    Malaria;   

Others  :  1125498
DOI  :  10.1186/s12916-014-0117-2

 received in 2014-03-14, accepted in 2014-06-19,  发布年份 2014

【 摘 要 】

Background

The RTS,S malaria vaccine is currently undergoing phase 3 trials. High vaccine-induced antibody titres to the circumsporozoite protein (CSP) antigen have been associated with protection from infection and episodes of clinical malaria.

Methods

Using data from 5,144 participants in nine phase 2 trials, we explore predictors of vaccine immunogenicity (anti-CSP antibody titres), decay in antibody titres, and the association between antibody titres and clinical outcomes. We use empirically-observed relationships between these factors to predict vaccine efficacy in a range of scenarios.

Results

Vaccine-induced anti-CSP antibody titres were significantly associated with age (P = 0.04), adjuvant (P <0.001), pre-vaccination anti-hepatitis B surface antigen titres (P = 0.005) and pre-vaccination anti-CSP titres (P <0.001). Co-administration with other vaccines reduced anti-CSP antibody titres although not significantly (P = 0.095). Antibody titres showed a bi-phasic decay over time with an initial rapid decay in the first three months and a second slower decay over the next three to four years. Antibody titres were significantly associated with protection, with a titre of 51 (95% Credible Interval (CrI): 29 to 85) ELISA units/ml (EU/mL) predicted to prevent 50% of infections in children. Vaccine efficacy was predicted to decline to zero over four years in a setting with entomological inoculation rate (EIR) = 20 infectious bites per year (ibpy). Over a five-year follow-up period at an EIR = 20 ibpy, we predict RTS,S will avert 1,782 cases per 1,000 vaccinated children, 1,452 cases per 1,000 vaccinated infants, and 887 cases per 1,000 infants when co-administered with expanded programme on immunisation (EPI) vaccines. Our main study limitations include an absence of vaccine-induced cellular immune responses and short duration of follow-up in some individuals.

Conclusions

Vaccine-induced anti-CSP antibody titres and transmission intensity can explain variations in observed vaccine efficacy.

【 授权许可】

   
2014 White et al.; licensee BioMed Central Ltd.

【 图 表 】

Fig. 3.

Figure 2.

Figure 3.

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