Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2017
Distinct Helper T Cell Type 1 and 2 Responses Associated With Malaria Protection and Risk in RTS,S/AS01E Vaccinees.
Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Duration and association with protection of NANP-repeat-specific and C-terminus-specific anti-circumsporozoite protein IgG responses following RTS,S/AS01The Lancet. Infectious diseases · 2026Trial
- Trial
- Differential Patterns of IgG Subclass Responses toFrontiers in immunology · 2019Trial
- Baseline exposure, antibody subclass, and hepatitis B response differentially affect malaria protective immunity following RTS,S/AS01E vaccination in African children.BMC medicine · 2018Trial
- Predictive signatures of immune response to vaccination and implications of the immune setpoint remodeling.mSphere · 2025Review
- Effect of RTS,S/AS01NPJ vaccines · 2024Article
- Article
- Immunological factors linked to geographical variation in vaccine responses.Nature reviews. Immunology · 2024Review
- Background malaria incidence and parasitemia during the three-dose RTS,S/AS01 vaccination series do not reduce magnitude of antibody response nor efficacy against the first case of malaria.BMC infectious diseases · 2023Article
- Cellular and antibody response in GMZ2-vaccinated Gabonese volunteers in a controlled human malaria infection trial.Malaria journal · 2022Article
- Review
- Article
- RTS,S/AS01 malaria vaccine (MosquirixDrugs & therapy perspectives : for rational drug selection and use · 2022Review
- Immune responses to malaria pre-erythrocytic stages: Implications for vaccine development.Parasite immunology · 2021Review
- Impacts of Ecology, Parasite Antigenic Variation, and Human Genetics on RTS,S/AS01e Malaria Vaccine Efficacy.Current epidemiology reports · 2021Review
- RTS,S/AS01 vaccine (Mosquirix™): an overview.Human vaccines & immunotherapeutics · 2020Article
- Modulation of innate immune responses at birth by prenatal malaria exposure and association with malaria risk during the first year of life.BMC medicine · 2018Article
- Article
- RTS,S/AS01E Malaria Vaccine Induces Memory and Polyfunctional T Cell Responses in a Pediatric African Phase III Trial.Frontiers in immunology · 2017Article
Corrections and comments
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Authors and funding
22 authors at 9 institutions in 7 countries.
Funding
Abstract
backgroundThe RTS,S/AS01E malaria vaccine has moderate efficacy, lower in infants than children. Current efforts to enhance RTS,S/AS01E efficacy would benefit from learning about the vaccine-induced immunity and identifying correlates of malaria protection, which could, for instance, inform the choice of adjuvants. Here, we sought cellular immunity-based correlates of malaria protection and risk associated with RTS,S/AS01E vaccination.
methodsWe performed a matched case-control study nested within the multicenter African RTS,S/AS01E phase 3 trial. Children and infant samples from 57 clinical malaria cases (32 RTS,S/25 comparator vaccinees) and 152 controls without malaria (106 RTS,S/46 comparator vaccinees) were analyzed. We measured 30 markers by Luminex following RTS,S/AS01E antigen stimulation of cells 1 month postimmunization. Crude concentrations and ratios of antigen to background control were analyzed.
resultsInterleukin (IL) 2 and IL-5 ratios were associated with RTS,S/AS01E vaccination (adjusted P ≤ .01). IL-5 circumsporozoite protein (CSP) ratios, a helper T cell type 2 cytokine, correlated with higher odds of malaria in RTS,S/AS01E vaccinees (odds ratio, 1.17 per 10% increases of CSP ratios; P value adjusted for multiple testing = .03). In multimarker analysis, the helper T cell type 1 (TH1)-related markers interferon-γ, IL-15, and granulocyte-macrophage colony-stimulating factor protected from subsequent malaria, in contrast to IL-5 and RANTES, which increased the odds of malaria.
conclusionsRTS,S/AS01E-induced IL-5 may be a surrogate of lack of protection, whereas TH1-related responses may be involved in protective mechanisms. Efforts to develop second-generation vaccine candidates may concentrate on adjuvants that modulate the immune system to support enhanced TH1 responses and decreased IL-5 responses.
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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.