Jorgen Stassijns1, Kaatje Bollaerts1, Marc Baay1, Thomas Verstraeten2. 1. P-95, Epidemiology and Pharmacovigilance Consulting and Services, Koning Leopold III Laan 1, 3001 Heverlee, Belgium. 2. P-95, Epidemiology and Pharmacovigilance Consulting and Services, Koning Leopold III Laan 1, 3001 Heverlee, Belgium. Electronic address: Thomas.Verstraeten@P-95.com.
Abstract
INTRODUCTION: New 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. METHODS: We 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. RESULTS: Twenty-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. CONCLUSIONS: Our 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.
INTRODUCTION: New 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. METHODS: We 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. RESULTS: Twenty-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. CONCLUSIONS: Our 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.
Authors: Adriana Bastidas; Javier de la Serna; Mohamed El Idrissi; Lidia Oostvogels; Philippe Quittet; Javier López-Jiménez; Filiz Vural; David Pohlreich; Tsila Zuckerman; Nicolas C Issa; Gianluca Gaidano; Je-Jung Lee; Sunil Abhyankar; Carlos Solano; Jaime Perez de Oteyza; Michael J Satlin; Stefan Schwartz; Magda Campins; Alberto Rocci; Carlos Vallejo Llamas; Dong-Gun Lee; Sen Mui Tan; Anna M Johnston; Andrew Grigg; Michael J Boeckh; Laura Campora; Marta Lopez-Fauqued; Thomas C Heineman; Edward A Stadtmauer; Keith M Sullivan Journal: JAMA Date: 2019-07-09 Impact factor: 56.272
Authors: Stephen C Dreskin; Neal A Halsey; John M Kelso; Robert A Wood; Donna S Hummell; Kathryn M Edwards; Jean-Christoph Caubet; Renata J M Engler; Michael S Gold; Claude Ponvert; Pascal Demoly; Mario Sanchez-Borges; Antonella Muraro; James T Li; Menachem Rottem; Lanny J Rosenwasser Journal: World Allergy Organ J Date: 2016-09-16 Impact factor: 4.084
Authors: Amanda L Wilkins; Dmitri Kazmin; Giorgio Napolitani; Elizabeth A Clutterbuck; Bali Pulendran; Claire-Anne Siegrist; Andrew J Pollard Journal: Front Immunol Date: 2017-12-13 Impact factor: 7.561