Diphtheria / Tetanus / Pertussis (acellular component) vaccine (adsorbed, reduced antigen(s) content) suspension for injection 0.5ml pre-filled syringes

ObjectiveTo systematically review and critically appraise human evidence on potential health effects of aluminium adjuvanted vaccines.DesignSystematic review following PRISMA (preferred reporting items for systematic review and meta-analysis) 2020 guidelines.Data sourcesSix databases and trial registries were searched from inception to 3 March 2023 then updated to 27 November 2025. Reference lists of eligible studies were also screened.Eligibility criteria for selecting studiesHuman studies assessing health outcomes after aluminium adjuvanted vaccination, including randomised controlled trials, cohort studies, case series, and ecological studies. Investigational vaccines, case reports, and review articles were excluded.Data extraction and synthesisTwo reviewers screened studies (with AI assistance for the 2023-25 update), extracted data, and assessed risk of bias (using RoB 2.0, ROBINS-I, or an adapted tool for case series). Certainty of evidence was rated using GRADE (Grading of Recommendations Assessment, Development, and Evaluation).ResultsThe review included 59 studies (37 case series, 11 randomised controlled trials, nine cohort studies, two ecological studies). High quality evidence from randomised controlled trials and large cohorts consistently showed no association between aluminium adjuvanted vaccines and serious or long term health outcomes, such as asthma, autism spectrum disorders, or other chronic conditions. Studies on macrophagic myofasciitis were generally small and methodologically limited, and did not provide credible evidence of a causal association (very low certainty). Localised persistent nodules or granulomas were observed infrequently after diphtheria-tetanus-pertussis vaccines, consistent with delayed type hypersensitivity (ConclusionsCurrent evidence does not support causal associations between aluminium adjuvanted vaccines and serious or long term health outcomes. The most consistently documented reactions were persistent nodules or granulomas that are uncommon, local, and self-limited hypersensitivity reactions. These findings are broadly consistent with post-licensure surveillance findings. The predominance of methodologically limited studies for some outcomes highlights the need for higher quality research.Systematic review registrationPROSPERO CRD42023462831.

Abstract licence: CC BY-NC

BackgroundAcute lymphoblastic leukemia is the most prevalent childhood cancer and the leading cause of cancer mortality before the age of 20. Although therapeutic advances have significantly improved survival, children and adolescents treated for acute lymphoblastic leukemia remain vulnerable to infections, largely preventable by vaccination, due to humoral and cellular immune dysfunction induced by disease and treatment.Materials and methodsThis systematic review, based on electronic databases, aims to evaluate antibody levels associated with potential protective immunity against vaccine antigens for diphtheria, pertussis, tetanus, poliomyelitis, Haemophilus influenzae type b, measles, mumps, rubella, influenza, varicella-zoster virus, yellow fever, pneumococcal, and meningococcal diseases in children and adolescents treated for acute lymphoblastic leukemia after completion of chemotherapy.ResultsA total of twenty-four studies published between 1981 and 2023 were included, comprising 1110 children and adolescents. Protective antibody levels ranged from 11% to 97% for diphtheria, 0% to 90% for pertussis, 20% to 100% for tetanus, and 11% to 95% for poliomyelitis. Haemophilus influenzae type b, protection ranged from 16.7% to 100%. Viral vaccines also showed heterogeneous responses, with protection rates of 25-79% for mumps, 16-86% for measles, 35-98% for rubella, and 23-75% for varicella-zoster virus. Antibody responses to pneumococcal and meningococcal vaccines were consistently low, with protection rates of 5-38% for pneumococcal studies and 12% in a single meningococcal study.ConclusionsThis review found a consistent and clinically relevant loss of vaccine-induced immunity in children and adolescents treated for acute lymphoblastic leukemia. The recommendation of vaccine booster doses for this vulnerable population, irrespective of serological status, may represent a more practical approach to ensuring adequate post-chemotherapy treatment protection.

Abstract licence: CC BY