In subunit vaccines, HA and NA have been further purified by removal of other viral components. In split virus vaccines, the virus has been disrupted by a detergent. There are three types of inactivated vaccines, the whole virus vaccines, split virus vaccines, and subunit vaccines. Two types of influenza vaccine are available, an inactivated (killed) preparation that is injected and an attenuated influenza vaccine normally delivered nasally. Due to the need to rapidly manufacture new vaccines in response to the likely strains that are identified, a unique set of regulatory requirements must be applied to the development, testing, and batch release of both seasonal and pandemic response influenza vaccines. The virus is grown in chick embryos or cell cultures for the production of vaccines. Reassortant strains for vaccine production have the surface glycoproteins (HA and NA) of the circulating epidemic virus but the internal proteins of a standardized production strain, eliminating much of the risks associated with handling pathogenic strains. It is now common practice to use reassortant strains for production that give high yields of the appropriate surface antigens. However, monovalent vaccines have been produced against candidate pandemic strains. In general, seasonal influenza vaccines are trivalent, containing a mixture of influenza A and B strains thought most likely to circulate in the coming season.

The World Health Organization reviews the world epidemiological situation twice annually and if necessary recommends new vaccine strain(s) in accordance with the available evidence. However, due to antigenic drift and antigenic shift, the protective effect of antibody induced by one strain may be reduced or lost as a function of time, resulting in individuals being relatively or completely unprotected against the new strains in circulation. HA is the major antigenic target of neutralizing antibodies. Protection against clinical disease is mainly conferred by serum antibodies, whereas mucosal IgA antibodies contribute to resistance against infection. An influenza pandemic is a rare but recurrent event. Secondary bacterial pneumonia is a frequent complication of influenza infection, particularly in elderly people and individuals with certain chronic diseases, resulting in a significant level of morbidity and mortality. Influenza is associated with considerable economic burden arising from health-care costs, lost days of work or education, and general social disruption across all age groups. Influenza occurs all over the world, with an annual global attack rate estimated at 5 – 10% in adults and 20 – 30% in children. Influenza virus is transmitted primarily by droplets or respiratory secretions of infected persons. Only type A and B cause human disease of any concern. Influenza B and C viruses mainly affect humans, whereas influenza A viruses infect a range of mammalian and avian species. Major changes in the influenza type A HA antigen ('antigenic shift') are caused by reassortment from different influenza A subtypes, such as between animal and human subtypes, and in rare events, such shifted viruses can result in strains capable of causing large regional or global pandemic outbreaks. Minor changes in the protein structure in influenza A strains ('antigenic drift') occur frequently, enabling the virus to cause repetitive influenza outbreaks by evading immune recognition.

Characteristic of many RNA genome viruses, influenza virus undergoes high mutation rates and frequent genetic reassortment (combination and rearrangement of genetic material) leading to variability in HA and NA antigens. Type A viruses are further subdivided according to their envelope glycoproteins with haemagglutinin (HA) or neuraminidase (NA) activity. The influenza viruses are classified into types A, B, and C on the basis of their core proteins. Influenza viruses belong to the family Orthomyxoviridae and have a single-stranded segmented RNA genome.

Antigenic shift