Influenza virus is a member of the Orthomyxoviridae family. There are three subtypes of influenza viruses designated A, B, and C that infect humans.
Seasonal epidemics of influenza can spread around the world quickly and inflict a significant economic burden in terms of hospital and other healthcare costs and lost productivity. The World Health Organization estimates that in annual influenza epidemics there are between three and five million cases of severe illness and approximately 250,000 and 500,000 deaths every year around the world.
An influenza pandemic occurs when a new influenza strain emerges in the population with high pathogenicity and antigenic novelty. Global pandemics can afflict between 20% and 40% of the world's population in a single year. The pandemic of 1918-19, for example, affected 200 million people, killing over 30 million worldwide. Although healthcare has dramatically improved since that time, with vaccines and antiviral therapies being developed, it is estimated that a pandemic today would result in two to seven million deaths globally.
In the event that an influenza pandemic were to occur, one problem that could arise is that it might be difficult to manufacture sufficient quantities of the influenza antigens required for use in vaccines in the required timescale. Another problem that could arise is that an influenza vaccines can take several weeks to confer immunity, which may not be quick enough to prevent or reduce the spread of a highly infection strain.
There is therefore a need for influenza antigens with increased immunogenicity, which could be used in smaller quantities and/or confer immunity more quickly than existing antigens.
WO 2011/121301, WO 2011/121306 and WO 2013/050780 are concerned with the use of particular excipients, including dialkylglycines and trialkylglycines such as dimethylglycine (DMG), for stabilising viral particles and/or polypeptides. WO 2011/121305 is concerned with the use of similar excipients for stabilising aluminium salt adjuvant during freezing or drying. None of these references are concerned with increasing the immunogenicity of influenza antigens.
Journal of Laboratory and Clinical Medicine (1990), 115(4), 481-6 by Reap et at describes the immunomodulating capabilities of dimethylglycine (DMG) in a rabbit model. The rabbits were force fed DMG prior to and after inoculation with an influenza antigen. Reap et at does not describe freezing, freeze-drying or heating the influenza antigen in the presence of DMG prior to administration to the rabbits.
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