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Vaccination against influenza represents our most effective form of prevention. Historical approaches toward vaccine creation and production have yielded highly effective vaccines that are safe and immunogenic. Despite their effectiveness, these historical approaches do not allow for the incorporation of changes into the vaccine in a timely manner. In 2013, a recombinant protein-based vaccine that induces immunity toward the influenza virus hemagglutinin was approved for use in the USA. This vaccine represents the first approved vaccine formulation that does not require an influenza virus intermediate for production. This review presents a brief history of influenza vaccines, with insight into the potential future application of vaccines generated using recombinant technology.

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.

Aging is associated with a decline in immune function (immunosenescence) that leads to progressive deterioration in both innate and adaptive immune functions. These changes contribute to the subsequent increased risk for infectious diseases and their sequelae. Vaccination is the most effective and inexpensive public health strategy for prevention of infection, despite the decreased efficacy of vaccines in older adults due to immunosenescence. The rapid rise in the older adult population globally represents a great challenge for vaccination programs. This article first addresses the status of innate and adaptive immune functions in aging and then focuses on influenza vaccine. The development history of influenza vaccines, current status, and potential strategies to improve the immunogenicity and vaccine effectiveness in older adults are discussed.