In a response to a request by the European Food Safety Agency, a panel on Animal Health and Welfare in conjunction with the European Union Reference Laboratory for Avian Influenza prepared a report on available vaccines and vaccination strategies against highly pathogenic avian influenza.  The terms of reference for the report published on Oct 10^th * considered:

• The range of available vaccines

• Specific approaches to vaccination given available data from the Netherlands, Italy and France.

At the outset it is noted that most of the published studies dealt with chickens although France acquired data on waterfowl with all three nations reporting information on vaccine efficacy and post-vaccination transmission.

The report outlined the characteristics of both inactivated adjuvanted oil emulsion vaccines, and vector vaccines that are both commercially available. More advanced nucleic acid products are currently under development. 

Vaccine efficiency was determined using a logistic regression model.  The study recognized that there is inadequate information on the duration of protection.  Generally, immunity in a flock is attained two weeks following primary administration but HVT-vectored vaccines required four weeks for durable protection.  Successive vaccinations using inactivated vaccine are required to protect domestic waterfowl. 

The model to determine that a vaccine would prevent sustained transmission showed a 0.82 probability of achieving 90 percent protection. This strongly suggests that most vaccines evaluated would reduce transmission of H5Nx clade 2.3.4.4b in chickens under experimental conditions.  Vaccine efficiency is dependent on antigenic match between vaccine strain and circulating field virus.  In evaluating serologic response, the report determined an association between HI titers and protection against transmission especially in chickens immunized with an inactivated vaccine.  This finding is consistent with the experience recently gained in Mexico where inactivated vaccines administered to flocks of laying hens was effective in decreasing the incidence rate of outbreaks. Subsequent reintroduction of virus into previously affected areas by migratory waterfowl was recently detected through surveillance. It will be interesting to ascertain whether previously immunized flocks are protected from inevitable field challenge.

Vaccine efficiency is influenced by host specific factors. In some situations inadequate flock immunity may lead to persistence of HPAI virus. Inadequate surveillance will allow undetected circulation of virus. 

The report concluded that there is no single vaccine that is applicable to all situations.  An additional complication is that most of the data used to prepare the report was based on laboratory and experimental studies that may presumably deviate from the situation in the field. Confounding factors under practical conditions included proximity of farms, distance of farms from wetlands that attract a high density of migratory waterfowl coupled with the population of commercial poultry on farms in an area.

With respect to vaccine strategy, the report considered:

• Emergency suppressive vaccination. This potential approach could be applied in the event of an outbreak on a specific farm in the absence of a program mandating depopulation with indemnity.  In the context of the U.S. and most commercial industries, rapid depopulation would be considered before immunization given the virulence of H5N1 and the need to prevent dissemination of virus from an affected farm to surrounding commercial poultry populations.  The report noted public concern over mass depopulation.  This is especially the case with ventilation shutdown that is engendering opposition even extending to proposed legislation to ban this method of euthanasia. This approach although faster and less labor intensive than using kill-carts flushed with carbon dioxide, is effectively inducing death by hyperthermia and respiratory alkalosis and requiring hours in large caged or aviary-housed flocks.

• Emergency protective vaccination. This approach would be carried out to protect non-exposed flocks following introduction of virus and to limit spread in the event of an outbreak in an area with a high density of poultry.

• Preventive vaccination in advance of introduction of infection. This would prevent spread of HPAI in an immunized population and hopefully maintain freedom from disease.  Preventive vaccination was evaluated in the context of the three E.U. nations and with special reference to areas in France with a history of recurring HPAI outbreaks.  It was determined that for all three nations, culling of infected farms resulted in the highest number of incident outbreaks and the longest duration of epornitics.  The application of preventive vaccination resulted in the lowest number of infected farms and the shortest duration based on available case studies.

The conclusions from the comprehensive study of available laboratory and field data showed:

• Although vaccines against avian influenza have been developed only a few are applied under commercial conditions suggesting the need for more comprehensive and expedited registration based on standards of efficacy and safety.

• The need for homogeneity among vaccines and circulating strains is an important consideration for programs applying inactivated vaccines.

• Preventive vaccination should be considered in high-risk areas to minimize outbreaks and epidemic duration. 

• The report demonstrated the potential for ring immunization over a two-mile radius around an index farm as a potentially effective method to establish immunity among flocks in an area and to limit the need for depopulation.
•  

Clearly conclusions from the EFSA Report are confirmed by the results from the traditional ‘whack-a-mole” approach by USDA-APHIS during the 2015 and 2022 epornitics. The disease was neither controlled nor eradicated. Incident cases ceased only when migration and hence shedding by waterfowl ended. Over 45 million egg producing hens were depopulated with 95 percent of this number on only 22 large complexes holding more than 0.5 million hens. The total number of infected commercial premises amounted to 41 locations in 11 states under all three migratory flyways. Mortality occurred in two waves coinciding with migration of waterfowl and with some collateral infection of non-migratory birds and mammals scavenging on dead waterfowl. 

Preventive vaccination is indicated in the U.S. in areas with a history of recurring infection among laying hens.  The dissemination of virus from complexes with upwards of two million hens in specific counties in Iowa, Colorado, Nebraska, Wisconsin and potentially in the future in Ohio and Indiana suggests the need for preventive vaccination as an adjunct to biosecurity. The imperative for preventive vaccination becomes even more obvious if H5N1 virus can be introduced onto farms by the aerosol route. Accepting this presumption based on anecdotal reports from cases in 2022 and the results of studies conducted during the Essex, U.K. 1972 Newcastle disease epornitic, even the most stringent structural and operational biosecurity will provide inadequate protection.

It appears that the fall-winter 2023 epornitic has commenced following the twelve outbreaks among turkey farms in four states. It is earnestly hoped that the October cases on commercial farms and in backyard flocks do not presage a repeat of 2022.  Given that migratory waterfowl and marine birds are both reservoirs and disseminators of avian influenza, the disease cannot be controlled or ever be eradicated simply by identifying and depleting infected flocks.

Previous editorials in EGG-NEWS have pointed to the futility of the current approach by APHIS in response to seasonal and regional outbreaks of HPAI. The costs to the public sector  and producers was probably in the region of $2 billion and consumers of eggs were obliged to pay an incremental $15 billion in 2022.  We are aware of the importance of the broiler export market valued at $5 billion in 2022 although this figure might be overstated if and when limited preventive vaccination of turkeys and egg production flocks is implemented. In the face of H5N1 infection that is effectively a panornitic since HPAI is present now on seven continents, acceptance of regional vaccination of specific types of poultry must be considered.  Neither Congress nor the public will continue to accept annual or recurring expenditures in attempts to suppress avian influenza with no reasonable prospect of eradication. The basic inhumanity of having to either depopulate or to countenance the potential depopulation of upwards of 50 million commercial poultry in each reoccurring epornitic is self-evident. Institutional and parochial intransigence against vaccination in the face of reality will soon become a more significant issue among consumers and in Congress hopefully leading to more effective structured strategies of prevention and control.

*Nielsen, S. et al. Vaccination of poultry against highly pathogenic avian influenza. Oct.10 2023, doi.org/10.2903/j.efsa.2023.8271