title: The safety evaluation of adjuvants during vaccine development: the AS04 experience.
abstract: Novel adjuvants that contain immunoenhancer molecules are now present in human vaccines either registered or in clinical trials. These adjuvants have the potential to provide clear benefits in improving the magnitude and duration of various aspects of the adaptive immune response. However, the use of immunoenhancers in vaccine formulations may be perceived as introducing theoretical safety risks that need to be addressed during the course of vaccine development. In addition to classical clinical safety evaluation, the licensing authorities recommend that novel adjuvants should be evaluated in non-clinical toxicology studies, both as separate entities and as part of the final vaccine formulation. We present here our approach for the safety evaluation of adjuvanted vaccines using AS04-adjuvanted vaccines as example. This evaluation consists of three tiers: non-clinical toxicology, adjuvant mode-of-action investigations and clinical safety assessment in controlled clinical trials and post-marketing surveillance. We also discuss how the knowledge of adjuvant mode of action can support the current practice of safety evaluation.
authors.affiliation: GlaxoSmithKline Biologicals, Avenue Fleming, 20, 1300 Wavre, Belgium. nathalie.garcon@gskbio.com
authors.forename: Nathalie
authors.initials: N
authors.lastname: Garçon
authors.forename: Lawrence
authors.initials: L
authors.lastname: Segal
authors.forename: Fernanda
authors.initials: F
authors.lastname: Tavares
authors.forename: Marcelle
authors.initials: M
authors.lastname: Van Mechelen
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D000818:Animals; D001327:Autoimmune Diseases / Q000453:epidemiology* / Q000209:etiology; D002648:Child; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D008050:Lipid A / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D011817:Rabbits; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D055815:Young Adult
chemical_list: C532963:ASO4 mixture; D000276:Adjuvants, Immunologic; D008050:Lipid A; D014765:Viral Vaccines; D000536:Aluminum Hydroxide