Influenza A viruses all originate from aquatic birds, which are their natural reservoir. From this vast, ever-present and global source they are able to cross the species barrier and infect a variety of hosts, including humans. Progressive viral adaptation of avian-origin viruses to novel hosts including domesticated birds, pigs, horses, dogs, or humans may result in widespread viral circulation and in the establishment of endemic viruses in a given population. In humans, influenza A infections usually are caused by endemic seasonal viruses and much less frequently by animal influenza viruses that cross the species barrier. A few times each century, some of the animal viruses also gain the capacity to sustain transmission among human populations, resulting in a pandemic. By definition, any emerging pandemic virus will be different antigenically from both human vaccine virus strains and contemporary human viruses, and so the human population will be immunologically naıve to a significant degree to the new virus before it spreads widely. To date, only viruses of the H1, H2, and H3 subtypes are known to have caused pandemics and establish subsequent global circulation.

It has been shown that all pandemic viruses emerging in the 20th century have had an avian influenza progenitor virus donating at least the haemagglutinin gene [1]. Since 1997, most scientific studies have focused on avian H5, and to a minor extent avian H7 and H9 subtype viruses, because these viruses have caused repeated zoonotic human infections and have spread widely in poultry over the past 10 years or more. So far, animal H1, H2, and H3 subtype viruses have been excluded from international research aiming at the development of pandemic vaccine candidates. The rationale for this is that the human population is considered sufficiently immune to H1 and H3 viruses due to exposure or vaccination against seasonal influenza viruses. In addition, the population over 40 years of age is largely immune to the H2 subtype viruses that circulated between 1957 and 1968.