ArticleThe Lancet. Infectious diseases2013
Efficacy of RTS,S malaria vaccines: individual-participant pooled analysis of phase 2 data.
Article in The Lancet. Infectious diseases, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 57 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 112 citations in OpenAlex.
- A systematic review on malaria and Tuberculosis (TB) vaccine challenges in sub-Saharan African clinical trials.PloS one · 2025Pooled it
- Peripheral blood monocyte-to-lymphocyte ratio at study enrollment predicts efficacy of the RTS,S malaria vaccine: analysis of pooled phase II clinical trial data.BMC medicine · 2013Pooled it
- Safety and High Level Efficacy of the Combination Malaria Vaccine Regimen of RTS,S/AS01B With Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara Vectored Vaccines Expressing ME-TRAP.The Journal of infectious diseases · 2016Trial
- 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 · 2015Trial
- Prime-boost vaccination with chimpanzee adenovirus and modified vaccinia Ankara encoding TRAP provides partial protection against Plasmodium falciparum infection in Kenyan adults.Science translational medicine · 2015Trial
- Impact of malaria preexposure on antiparasite cellular and humoral immune responses after controlled human malaria infection.Infection and immunity · 2015Trial
- Evaluation of the efficacy of ChAd63-MVA vectored vaccines expressing circumsporozoite protein and ME-TRAP against controlled human malaria infection in malaria-naive individuals.The Journal of infectious diseases · 2015Trial
- Memory B-cell and antibody responses induced by Plasmodium falciparum sporozoite immunization.The Journal of infectious diseases · 2014Trial
- Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination: a phase 3 randomized, controlled trial in children and young infants at 11 African sites.PLoS medicine · 2014Trial
- CXCR6+ CD127- Tr1 cells balance immunity and persistence in Plasmodium falciparum infection.The Journal of clinical investigation · 2026Article
- A functional crosstalk between circulating follicular helper 2 T cells and memory B cells drives anti-Plasmodium vivax antibodies.PLoS neglected tropical diseases · 2026Article
- Public health impact of catch-up vaccination or additional booster doses with pre-erythrocytic malaria vaccine R21/Matrix-M: a modelling study.BMC medicine · 2026Article
- A Plasmodium-derived nanoparticle vaccine elicits sterile protection against malaria in mice.Nature microbiology · 2026Article
- CXCR6bioRxiv : the preprint server for biology · 2025Article
- Epitope and HLA specificity of human TCRs against Plasmodium falciparum circumsporozoite protein.The Journal of experimental medicine · 2025Article
- Heterogeneity of the human immune response to malaria infection and vaccination driven by latent cytomegalovirus infection.EBioMedicine · 2024Article
- Malaria vaccine efficacy, safety, and community perception in Africa: a scoping review of recent empirical studies.Infection · 2024Article
- Monoclonal antibodies to the circumsporozoite proteins as an emerging tool for malaria prevention.Nature immunology · 2024Review
- Poly I:C elicits broader and stronger humoral and cellular responses to aFrontiers in immunology · 2024Article
- Immunogenicity, Efficacy, and Safety of a Novel Synthetic Microparticle Pre-Erythrocytic Malaria Vaccine in Multiple Host Species.Vaccines · 2023Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
12 authors at 8 institutions in 7 countries.
Funding
Abstract
backgroundThe efficacy of RTS,S/AS01 as a vaccine for malaria is being tested in a phase 3 clinical trial. Early results show significant, albeit partial, protection against clinical malaria and severe malaria. To ascertain variations in vaccine efficacy according to covariates such as transmission intensity, choice of adjuvant, age at vaccination, and bednet use, we did an individual-participant pooled analysis of phase 2 clinical data.
methodsWe analysed data from 11 different sites in Africa, including 4453 participants. We measured heterogeneity in vaccine efficacy by estimating the interactions between covariates and vaccination in pooled multivariable Cox regression and Poisson regression analyses. Endpoints for measurement of vaccine efficacy were infection, clinical malaria, severe malaria, and death. We defined transmission intensity levels according to the estimated local parasite prevalence in children aged 2-10 years (PrP₂₋₁₀), ranging from 5% to 80%. Choice of adjuvant was either AS01 or AS02.
findingsVaccine efficacy against all episodes of clinical malaria varied by transmission intensity (p=0·001). At low transmission (PrP₂₋₁₀ 10%) vaccine efficacy was 60% (95% CI 54 to 67), at moderate transmission (PrP₂₋₁₀ 20%) it was 41% (21 to 57), and at high transmission (PrP₂₋₁₀ 70%) the efficacy was 4% (-10 to 22). Vaccine efficacy also varied by adjuvant choice (p<0·0001)--eg, at low transmission (PrP₂₋₁₀ 10%), efficacy varied from 60% (95% CI 54 to 67) for AS01 to 47% (14 to 75) for AS02. Variations in efficacy by age at vaccination were of borderline significance (p=0·038), and bednet use and sex were not significant covariates. Vaccine efficacy (pooled across adjuvant choice and transmission intensity) varied significantly (p<0·0001) according to time since vaccination, from 36% efficacy (95% CI 24 to 45) at time of vaccination to 0% (-38 to 38) after 3 years.
interpretationVaccine efficacy against clinical disease was of limited duration and was not detectable 3 years after vaccination. Furthermore, efficacy fell with increasing transmission intensity. Outcomes after vaccination cannot be gauged accurately on the basis of one pooled efficacy figure. However, predictions of public-health outcomes of vaccination will need to take account of variations in efficacy by transmission intensity and by time since vaccination.
fundingMedical Research Council (UK); Bill & Melinda Gates Foundation Vaccine Modelling Initiative; Wellcome Trust.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.