A systematic review and meta-analysis on the safety of newly adjuvanted vaccines among children |
| |
| Affiliation: | 1. Department of Pediatrics, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA;2. Departments of Microbiology & Immunology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA;3. Department of Biostatistics, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA;4. Department of Medicine, Emory University School of Medicine, 1648 Pierce Drive NE, Atlanta, GA 30307, USA;1. Karolinska Institutet, Department of Medicine, Unit of Infectious Diseases, Karolinska Solna, Stockholm, Sweden;2. Department of Communicable Disease Control and Prevention, Stockholm County Council, Box 175 33, SE-118 91 Stockholm, Sweden;3. Astrid Lindgren Children''s Hospital, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden;4. Sachs’ Children and Youth Hospital, Stockholm South General Hospital, Sjukhusbacken 10, SE-118 83 Stockholm, Sweden;5. Astrid Lindgren Children''s Hospital, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden;1. LiteVax BV, Oss, The Netherlands;2. Biomedical Primate Research Centre, Rijswijk, The Netherlands;3. Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands;4. Viroclinics Biosciences BV, Rotterdam, The Netherlands;1. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA;2. Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA;3. Institute for Biomedical Sciences, George Washington University, Washington, DC, USA;4. Institute for Asthma and Allergy, Chevy Chase, MD, USA;5. Commissioned Corps, US Public Health Service, Rockville, MD, USA |
| |
| Abstract: | IntroductionNew adjuvants such as the AS- or the MF59-adjuvants improve vaccine efficacy and facilitate dose-sparing. Their use in influenza and malaria vaccines has resulted in a large body of evidence on their clinical safety in children.MethodsWe carried out a systematic search for safety data from published clinical trials on newly adjuvanted vaccines in children ≤10 years of age. Serious adverse events (SAEs), solicited AEs, unsolicited AEs and AEs of special interest were evaluated for four new adjuvants: the immuno-stimulants containing adjuvant systems AS01 and AS02, and the squalene containing oil-in-water emulsions AS03 and MF59. Relative risks (RR) were calculated, comparing children receiving newly adjuvanted vaccines to children receiving other vaccines with a variety of antigens, both adjuvanted and unadjuvanted.ResultsTwenty-nine trials were included in the meta-analysis, encompassing 25,056 children who received at least one dose of the newly adjuvanted vaccines. SAEs did not occur more frequently in adjuvanted groups (RR 0.85, 95%CI 0.75–0.96). Our meta-analyses showed higher reactogenicity following administration of newly adjuvanted vaccines, however, no consistent pattern of solicited AEs was observed across adjuvant systems. Pain was the most prevalent AE, but often mild and of short duration. No increased risks were found for unsolicited AEs, febrile convulsions, potential immune mediated diseases and new onset of chronic diseases.ConclusionsOur meta-analysis did not show any safety concerns in clinical trials of the newly adjuvanted vaccines in children ≤10 years of age. An unexplained increase of meningitis in one Phase III AS01-adjuvanted malaria trial and the link between narcolepsy and the AS03-adjuvanted pandemic vaccine illustrate that continued safety monitoring is warranted. |
| |
| Keywords: | Vaccine Adjuvants Safety Children |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
