ABSTRACT
With the exception of alum, emulsion-based vaccine adjuvants have been administered to far more people than any other adjuvant, especially since the 2009 H1N1 influenza pandemic. The number of clinical safety and immunogenicity evaluations of vaccines containing emulsion adjuvants has correspondingly mushroomed. In this review, the authors introduce emulsion adjuvant composition and history before detailing the most recent findings from clinical and postmarketing data regarding the effects of emulsion adjuvants on vaccine immunogenicity and safety, with emphasis on the most widely distributed emulsion adjuvants, MF59® and AS03. The authors also present a summary of other emulsion adjuvants in clinical development and indicate promising avenues for future emulsion-based adjuvant development. Overall, emulsion adjuvants have demonstrated potent adjuvant activity across a number of disease indications along with acceptable safety profiles.
Subject(s)
Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/adverse effects , Emulsions/administration & dosage , Emulsions/adverse effects , Vaccines/adverse effects , Vaccines/immunology , Adjuvants, Immunologic/chemistry , Adjuvants, Immunologic/history , Clinical Trials as Topic , Drug Combinations , Emulsions/chemistry , Emulsions/history , History, 20th Century , History, 21st Century , Humans , Polysorbates/administration & dosage , Polysorbates/adverse effects , Polysorbates/chemistry , Polysorbates/history , Product Surveillance, Postmarketing , Squalene/administration & dosage , Squalene/adverse effects , Squalene/chemistry , Squalene/history , Vaccines/administration & dosage , alpha-Tocopherol/administration & dosage , alpha-Tocopherol/adverse effects , alpha-Tocopherol/chemistry , alpha-Tocopherol/historyABSTRACT
The first clinical trial of an MF59(®)-adjuvanted influenza vaccine (Novartis) was conducted 20 years ago in 1992. The product that emerged (Fluad(®), Novartis) was licensed first in Italy in 1997 and is now licensed worldwide in 30 countries. US licensure is expected in the coming years. By contrast, many alternative adjuvanted vaccines have failed to progress. The key decisions that allowed MF59 to succeed in such a challenging environment are highlighted here and the lessons that were learned along the way are discussed. MF59 was connected to vaccines that did not succeed and was perceived as a 'failure' before it was a success. Importantly, it never failed for safety reasons and was always well tolerated. Even when safety issues have emerged for alternative adjuvants, careful analysis of the substantial safety database for MF59 have shown that there are no significant concerns with widespread use, even in more 'sensitive' populations.
