Current status and progress of prepandemic and pandemic influenza vaccine development

H5N1 viruses are widely considered to be a probable cause of the next influenza pandemic. Influenza vaccines are considered to form the main prophylactic measure against pandemic influenza. The world's population is expected to have no pre-existing immunity against the pandemic virus strain and will need two vaccine doses to acquire protective immunity. A pandemic outbreak will spread much faster than it will take for pandemic vaccines to be produced and distributed. Therefore, increasing efforts are being made to develop prepandemic vaccines that can induce broad cross-protective responses and that can be administered as soon as a pandemic is declared or even before, in order to successfully prime the immune system and allow for a rapid and protective antibody response with one dose of the pandemic vaccine. Several vaccine manufacturers have developed candidate pandemic and prepandemic vaccines, predominantly based on reverse-genetics reference strains and have improved the immunogenicity by formulating these vaccines with different adjuvants. Clinical studies with inactivated split-virion or whole-virion vaccines based on H5N1 indicate that two immunizations appear necessary to elicit the level of immunity required to meet licensure criteria. A detailed overview is given of the most successful candidate vaccines developed by seven vaccine manufacturers.