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Effect of RTS,S/AS01E vaccine booster dose on cellular immune responses in African infants and children
Robert A Mitchell1,2, Dídac Macià1,2,3, Chenjerai Jairoce1,2,4
1ISGlobal, Barcelona, Catalonia, Spain.
Insights
The RTS,S/AS01E malaria vaccine booster dose elicits moderate cell-mediated immune responses. These responses, particularly IL-2, correlate with reduced malaria risk and sustained antibody levels, supporting vaccine efficacy.
Area of Science:
- Immunology
- Vaccinology
- Infectious Diseases
Background:
- The RTS,S/AS01E malaria vaccine showed moderate efficacy in Phase 3 trials.
- Previous studies assessed cell-mediated immune (CMI) responses after primary immunization.
- Understanding responses to booster doses is crucial for long-term vaccine effectiveness.
Purpose of the Study:
- To evaluate CMI responses following an 18-month-delayed booster dose of the RTS,S/AS01E malaria vaccine.
- To assess the association of these CMI responses with malaria risk and antibody levels post-booster.
Main Methods:
- Peripheral blood mononuclear cells from 709 children and infants were stimulated with RTS,S/AS01E antigen.
- Thirty CMI markers were quantified using Luminex assays.
- Associations with malaria incidence and anti-circumsporozoite protein (CSP) IgG levels were analyzed.
Main Results:
- RTS,S/AS01E booster vaccination was associated with increased levels of IL-2, IFN-γ, IL-17, IL-5, and IL-13.
- IL-2 responses to CSP remained elevated one year post-booster.
- Higher IL-2 levels correlated with reduced malaria risk at one site, while IL-10 was linked to increased risk in infants.
Conclusions:
- The RTS,S/AS01E booster dose induces a moderate CMI response.
- Sustained IL-2 responses and their association with reduced malaria risk suggest a role in maintaining vaccine-induced protection.
- These findings align with the partial recovery of RTS,S/AS01E vaccine efficacy observed previously.
Abstract:
RTS,S/AS01E, the first approved malaria vaccine, demonstrated moderate efficacy during the phase 3 pediatric trial. We previously investigated cell-mediated immune (CMI) responses following the primary 3-dose immunization and now report responses to the booster dose given 18 months later. Thirty CMI markers were measured by Luminex in supernatants of peripheral blood mononuclear cells from 709 children and infants after RTS,S/AS01E antigen stimulation, and their associations with malaria risk and antibodies one month post-booster and one year later were assessed. IL-2, IFN-γ, IL-17, IL-5, and IL-13 were associated with RTS,S/AS01E booster vaccination, and IL-2 responses to the circumsporozoite protein (CSP) remained higher after one year. IL-2 was associated with reduced malaria risk in one site, and IL-10 was associated with increased risk in infants. Anti-CSP IgG and IL-2 were moderately correlated one year after booster. This study highlights the moderate cell-mediated immunogenicity of the RTS,S/AS01E booster dose that aligns with partial recovery of RTS,S/AS01E vaccine efficacy.
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