Trial reportPloS one2011
Circumsporozoite-specific T cell responses in children vaccinated with RTS,S/AS01E and protection against P falciparum clinical malaria.
Trial report in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00380393 (A Study of the Efficacy Against Episodes of Clinical Malaria Due to P. Falciparum Infection of GSK Biologicals Candidate Vaccine RTS,S/AS01, Administered According to a 0,1,2-months Schedule in Children Aged 5 to 17 Months Living in Tanzania & Kenya), which is not on this map. Cited by 62 papers, 1 of them a synthesis 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.
A Study of the Efficacy Against Episodes of Clinical Malaria Due to P. Falciparum Infection of GSK Biologicals Candidate Vaccine RTS,S/AS01, Administered According to a 0,1,2-months Schedule in Children Aged 5 to 17 Months Living in Tanzania & Kenya
Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- 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
- The Anti-Circumsporozoite Antibody Response of Children to Seasonal Vaccination With the RTS,S/AS01E Malaria Vaccine.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Trial
- Multifunctional Antibodies Are Induced by the RTS,S Malaria Vaccine and Associated With Protection in a Phase 1/2a Trial.The Journal of infectious diseases · 2021Trial
- Distinct Helper T Cell Type 1 and 2 Responses Associated With Malaria Protection and Risk in RTS,S/AS01E Vaccinees.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2017Trial
- Effective Antimalarial Chemoprevention in Childhood Enhances the Quality of CD4+ T Cells and Limits Their Production of Immunoregulatory Interleukin 10.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
- IFNγ Responses to Pre-erythrocytic and Blood-stage Malaria Antigens Exhibit Differential Associations With Past Exposure and Subsequent Protection.The Journal of infectious diseases · 2015Trial
- Ad35.CS.01-RTS,S/AS01 Heterologous Prime Boost Vaccine Efficacy against Sporozoite Challenge in Healthy Malaria-Naïve Adults.PloS one · 2015Trial
- Avidity of anti-circumsporozoite antibodies following vaccination with RTS,S/AS01E in young children.PloS one · 2014Trial
- IFNγ/IL-10 co-producing cells dominate the CD4 response to malaria in highly exposed children.PLoS pathogens · 2014Trial
- Evaluation of the immune response to RTS,S/AS01 and RTS,S/AS02 adjuvanted vaccines: randomized, double-blind study in malaria-naïve adults.Human vaccines & immunotherapeutics · 2014Trial
- Randomized, placebo-controlled trial to assess the safety and immunogenicity of an adenovirus type 35-based circumsporozoite malaria vaccine in healthy adults.Human vaccines & immunotherapeutics · 2013Trial
- Trial
- TEpiNom: A computational framework integrating population data to prioritize Plasmodium falciparum T cell epitopes.Vaccine · 2026Article
- Engineering strategies and decision frameworks for virus-like particle-based vaccines against infectious diseases.Frontiers in microbiology · 2026Review
- CD4 T cell phenotype after AS01-adjuvanted immunization is shaped by prior antigen or pathogen exposure.Frontiers in immunology · 2026Article
- The anti-circumsporozoite antibody response to repeated, seasonal booster doses of the malaria vaccine RTS,S/AS01NPJ vaccines · 2025Article
- Effect of RTS,S/AS01NPJ vaccines · 2024Article
- Malaria vaccines: the 60-year journey of hope and final success-lessons learned and future prospects.Tropical medicine and health · 2023Review
- Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 4 countries.
Funding
Abstract
backgroundRTS,S/AS01(E) is the lead candidate pre-erythrocytic malaria vaccine. In Phase IIb field trials the safety profile was acceptable and the efficacy was 53% (95%CI 31%-72%) for protecting children against clinical malaria caused by P. falciparum. We studied CS-specific T cell responses in order to identify correlates of protection. METHODS AND
findingsWe used intracellular cytokine staining (for IL2, IFNγ, and TNFα), ex-vivo ELISPOTs (IFNγ and IL2) and IFNγ cultured ELISPOT assays to characterize the CS-specific cellular responses in 407 children (5-17 months of age) in a phase IIb randomized controlled trial of RTS,S/AS01(E) (NCT00380393). RTS,S/ AS01(E) vaccinees had higher frequencies of CS-specific CD4+ T cells producing IFNγ, TNFα or IL2 compared to control vaccinees. In a multivariable analysis TNFα(+) CD4(+) T cells were independently associated with a reduced risk for clinical malaria among RTS,S/AS01(E) vaccinees (HR = 0.64, 95%CI 0.49-0.86, p = 0.002). There was a non-significant tendency towards reduced risk among control vaccinees (HR = 0.80, 95%CI 0.62-1.03, p = 0.084), albeit with lower CS-specific T cell frequencies and higher rates of clinical malaria. When data from both RTS,S/AS01(E) vaccinees and control vaccinees were combined (with adjusting for vaccination group), the HR was 0.74 (95%CI 0.62-0.89, p = 0.001). After a Bonferroni correction for multiple comparisons (n-18), the finding was still significant at p = 0.018. There was no significant correlation between cultured or ex vivo ELISPOT data and protection from clinical malaria. The combination of TNFα(+) CD4(+) T cells and anti-CS antibody statistically accounted for the protective effect of vaccination in a Cox regression model.
conclusionsRTS,S/AS01(E) induces CS-specific Th1 T cell responses in young children living in a malaria endemic area. The combination of anti-CS antibody concentrations titers and CS-specific TNFα(+) CD4(+) T cells could account for the level of protection conferred by RTS,S/AS01(E). The correlation between CS-specific TNFα(+) CD4(+) T cells and protection needs confirmation in other datasets.
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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.