Avian influenza causes two forms of disease in poultry, one common and mild, the other rare but highly lethal. While 16 HA and 9 NA virus subtypes infect birds, the highly pathogenic viruses (HPAI) are typically H5 and H7 subtypes. Avian influenza viruses are normally species specific, but five strains (H5N1, H7N3, H7N7, H7N9 and H9N2) have infected humans. H5N1 virus can cause severe disease and death in humans, and has appeared in more than 60 countries across Asia, Europe and Africa. H5N1 spreads rapidly in bird populations worldwide and there is great concern that this virus will begin to transmit between humans and cause a global pandemic. However, no information is available on the likelihood of occurrence of an H5N1 pandemic and the severity of such a pandemic.
Based on limited epidemiological data, the overall risk of HPAI H5N1 virus transmission to humans following exposure to the virus appears to be very low. The key factors are the intensity of exposure to the virus, potentially modifiable factors such as behaviour or use of protective equipment, and possibly other unknown host factors.
Vaccines are the cornerstone strategy for combating avian influenza. However, there are challenges for pandemic preparedness including the unpredictability of the vaccine target, the potential production capacity for pandemic vaccine, manufacturing requirement for rapid deployment, as well as expiry of stockpiled vaccines during interpandemic period.
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:
- GlaxoSmithKline’s vaccine Prepandrix® approved by the European Union in May 2008.
- CSL Limited’s vaccine Panvax® approved by Australia in June 2008.
- 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.
Clegg, C. H., Rininger, J. A., & Baldwin, S. L. (2013). Clinical vaccine development for H5N1 influenza. Expert review of vaccines, 12(7), 767–777. https://doi.org/10.1586/14760584.2013.811178
- Steel J. (2011). New strategies for the development of H5N1 subtype influenza vaccines: progress and challenges. BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 25(5), 285–298. https://doi.org/10.1007/BF03256169
- Strategic Advisory Group of Experts. (2009). Report of the H5N1 SAGE Working Group to the April 2009 meeting. Use of licensed H5N1 influenza vaccines in the interpandemic period. Available at https://www.who.int/immunization/sage/SAGE_ H5N1_26Mayb.pdf. Accessed April 2019.