The history of MF59^® adjuvant: a phoenix that arose from the ashes

Abstract

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.

Keywords::

• emulsion
• influenza vaccine
• MF59®
• pandemic influenza vaccine
• vaccine adjuvant

Acknowledgements

The authors are grateful to the many collaborators and colleagues who have worked with them over the years and who have contributed significantly to the success of MF59. Most notably, the authors are grateful to the exceptional work of A Podda who led the clinical development of Fluad^® (Novartis). The authors are grateful for the insight and advice of T Tsai in writing this review. DT O’Hagan is also grateful for the initial suggestion of E Pronker to write this history, so that others may learn. The authors are grateful to K Karklins for formatting and submission.

Financial & competing interests disclosure

DT O’Hagan, G Del Guidice and R Rappouli are employees of Novartis Vaccines. GS Ott and G Van Nest are former employees of Chiron Vaccines and now of Dynavax and MedImmune, respectively. G Van Nest and GS Ott have no affliation or financial interest (including stock ownership) with Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.