The initial H5N1 vaccines were produced using the same manufacturing methods and regulatory approval criteria as seasonal influenza vaccines, which involves production of a virus seed stock optimised for growth in chicken eggs and inactivation. The inactivated H5N1 vaccines are poorly immunogenic and are inefficiently produced. New vaccine technologies are under research, which will maximise antigen activity and expedite vaccine supply. New egg-independent vaccine antigens that appear effective in human clinical trials include cell-based virus production, recombinant protein and virus-like particles. Vaccine adjuvants augment adaptive immunity and are being used to broaden antibody responses against different strains of virus and to improve vaccine dose-sparing. 

Several H5N1 influenza vaccines have been registered for use in interpandemic period, such as the following:

1. GlaxoSmithKline’s vaccine Prepandrix® approved by the European Union in May 2008.
2. CSL Limited’s vaccine Panvax® approved by Australia in June 2008.
3. Sanofi Pasteur’s vaccine approved by the United States in April 2017.

The use of the vaccines during in interpandemic period should be based on risk assessment:

• Vaccination with licensed H5N1 vaccine is strongly recommended for laboratory workers involved in the following activities:
  » large-scale production or manipulation of HPAI H5N1 virus;
  » working with the virus over a long period;
  » working with HPAI H5N1 virus strains that are resistant to licensed antiviral compounds;
  » working with virus strains with the potential for increased transmissibility in mammalian species.

For laboratory personnel working with H5N1 virus, but not involved in these activities, the risks and benefits associated with H5N1 vaccination should be evaluated.

• Vaccine may be made available to HCWs in countries where avian H5N1 virus is enzootic and where human cases may continue to emerge and pose the threat of exposure for HCWs.

• Vaccination is recommended for HCWs who evaluate or manage suspected or confirmed H5N1 patients in designated outpatient or inpatient referral facilities.
• Vaccination is recommended for workers involved in a first response to possible H5N1 outbreaks in animals or humans, depending on the assumed risk of exposure and type of activities.
• Vaccine may be made available as a preventive measure to the relatively few persons in contact with poultry in confirmed active outbreak areas, depending on the level of enzooticity, risk of exposure and effectiveness of other prevention measures in place.
• The risk of infection in the general public remains very low. Since one cannot exclude a risk, albeit low, of vaccine-related serious adverse events, and at the present low level of risk of infection, H5N1 vaccination is not recommended currently in the general population.

Vaccines are critical for preventing influenza disease, but significant scientific and economic challenges remain in providing universal coverage of a pandemic influenza vaccine on a global scale. Vaccine development is challenged by the unpredictability of the emerging strain of virus, the fact that humans will likely not be immune to the virus, and that manufacturing capacity will be insufficient to meet worldwide demand. Better, faster and more efficient ways are under study in vaccines development. There is a need for new recombinant-based vaccines and adjuvants that can maximise immunogenicity, shorten production cycles and satisfy global demand. All available technologies will be needed in order to produce a world supply of vaccine within 6 months of a pandemic outbreak. A careful risk assessment is required for H5N1 vaccination during interpandemic period.