Clinical efficacy, immunogenicity and safety of Malaria vaccines in children: a systematic review and meta-analysis
1
Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, Rome, Italy
Popul. Med. 2026;8(Supplement Supplement 1):
ABSTRACT
BACKGROUND:
Malaria remains a major global health emergency, with nearly 610.000 deaths reported in 2024 across 83 countries, with children under five accounting for 75% of mortality. Despite increased research on pediatric malaria vaccines, comprehensive evidence syntheses are limited. We aimed to assess the efficacy and safety of currently available malaria vaccines in children.
METHODS:
Following PRISMA, we included Phase IIb–IV and post-marketing studies from PubMed, SCOPUS, WoS, ClinicalTrials.gov, ISRCTN, EUCTR, CTIS, and PACTR. Licensed and candidate vaccines administered to individuals <18 years were compared with controls or seasonal malaria chemoprevention. Outcomes included seroconversion, incidence of clinical malaria, and serious adverse events (SAEs). Meta-analyses were performed for the intention-to-treat cohorts, with subgroup analyses by vaccine type and follow-up (PROSPERO registration: CRD420251032609).
RESULTS:
56 trials were included (134.424 participants). The proportional meta-analysis revealed an overall SAE rate of 16%, higher for RTS,S/AS02 (29%) and lower for R21-MM (3%). In comparative analyses, vaccination reduced SAEs risk by 9% versus controls (RR=0.91; 95% CI 0.86–0.96). Overall vaccine efficacy (VE) was 31% (IRR=0.69), higher for RTS,S/AS02 (47%) and RTS,S/AS01 (32%). R21/Matrix-M demonstrated the highest VE (72%, single trial). Efficacy declined with time: 33% within 12 months, 35% at 12–36 months, and 11% beyond 36 months. The combination of vaccination and chemoprevention showed 65% efficacy. Cumulative seroconversion rate was 0.99 (95% CI 0.98–1.00). Comparative seroconversion analysis was not feasible due to absent control data. No study was rated as low quality by RoB2.
CONCLUSIONS:
Malaria vaccines in children show a favorable safety profile and provide meaningful, although time-limited, protection against clinical malaria. RTS,S and R21 vaccines achieve the highest efficacy, particularly when combined with seasonal chemoprevention. Malaria vaccination should be integrated into childhood malaria control strategies, emphasizing the need for booster strategies and long-term effectiveness monitoring in endemic settings.
Malaria remains a major global health emergency, with nearly 610.000 deaths reported in 2024 across 83 countries, with children under five accounting for 75% of mortality. Despite increased research on pediatric malaria vaccines, comprehensive evidence syntheses are limited. We aimed to assess the efficacy and safety of currently available malaria vaccines in children.
METHODS:
Following PRISMA, we included Phase IIb–IV and post-marketing studies from PubMed, SCOPUS, WoS, ClinicalTrials.gov, ISRCTN, EUCTR, CTIS, and PACTR. Licensed and candidate vaccines administered to individuals <18 years were compared with controls or seasonal malaria chemoprevention. Outcomes included seroconversion, incidence of clinical malaria, and serious adverse events (SAEs). Meta-analyses were performed for the intention-to-treat cohorts, with subgroup analyses by vaccine type and follow-up (PROSPERO registration: CRD420251032609).
RESULTS:
56 trials were included (134.424 participants). The proportional meta-analysis revealed an overall SAE rate of 16%, higher for RTS,S/AS02 (29%) and lower for R21-MM (3%). In comparative analyses, vaccination reduced SAEs risk by 9% versus controls (RR=0.91; 95% CI 0.86–0.96). Overall vaccine efficacy (VE) was 31% (IRR=0.69), higher for RTS,S/AS02 (47%) and RTS,S/AS01 (32%). R21/Matrix-M demonstrated the highest VE (72%, single trial). Efficacy declined with time: 33% within 12 months, 35% at 12–36 months, and 11% beyond 36 months. The combination of vaccination and chemoprevention showed 65% efficacy. Cumulative seroconversion rate was 0.99 (95% CI 0.98–1.00). Comparative seroconversion analysis was not feasible due to absent control data. No study was rated as low quality by RoB2.
CONCLUSIONS:
Malaria vaccines in children show a favorable safety profile and provide meaningful, although time-limited, protection against clinical malaria. RTS,S and R21 vaccines achieve the highest efficacy, particularly when combined with seasonal chemoprevention. Malaria vaccination should be integrated into childhood malaria control strategies, emphasizing the need for booster strategies and long-term effectiveness monitoring in endemic settings.
| eISSN: | 2654-1459 |
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