With millions of commercially raised birds affected by avian influenza in thousands of facilities in major poultry-producing countries worldwide, the call for a truly effective solution is growing stronger, and vaccination is becoming the most likely scenario. So far, governments have been hesitant to launch vaccination programs, primarily due to the potential impact it could have on poultry trade. However, France has now launched a tender for 80 million doses of avian influenza vaccines as the country prepares to start a vaccination program this autumn. This is the first EU member to initiate such a scheme, as reported by Reuters, which analyzed the evolving situation of avian influenza.

Adopting a preventive vaccination strategy

Many countries in Europe have been affected by avian influenza. However, as noted by Poultry World in August 2022, among the poultry outbreaks up to that point, the country most severely affected was France, accounting for 68% of recent cases. The country has remained the hardest hit by avian influenza among all EU member states, with over 21 million birds culled.

Currently, the pre-order, which will be confirmed if the final test results are positive, focuses only on vaccinating ducks. France has mandated two companies, Animal Health and Boehringher Ingelheim from Germany, to develop avian influenza vaccines. Both vaccines have proven effective in protecting birds against the virus itself and, more importantly, preventing the shedding of the virus by the birds.

"Health crises caused by avian influenza have been repeated and have increased in magnitude, which means that preventive measures on poultry farms need to be strengthened," said the French health and safety agency, ANSES. The agency emphasized that vaccination should be seen as a measure complementing the biosecurity preventive measures implemented in the field.

ANSES, entrusted with presenting a series of vaccination strategies, cautioned against emergency vaccination. Caroline Boudergue, Deputy Head of the ANSES Unit for Risk Assessment Associated with Animal and Vector Health, Welfare, and Nutrition, stated, "We did not choose the option of emergency vaccination due to the long period between vaccinating an animal and its protection against the virus. It takes approximately 3-4 weeks for this immunity to be acquired. Moreover, vaccinating animals in the midst of an animal epidemic tends to increase human traffic on farms and, therefore, the risk of biosecurity breaches."

Vaccination Scenarios

ANSES has proposed three scenarios regarding the risk of introduction and spread of highly pathogenic avian influenza, based on a graded approach using available vaccination means:

Scenario 1: Vaccinate animals present in nucleus and multiplier farms across all sectors. This step has the advantage of requiring a limited number of vaccine doses. Additionally, vaccination can protect the poultry sectors from the impact of a new animal epidemic by preserving the genetic potential and the capacity to reintroduce animals into production farms once the epidemic has ended.

Scenario 2: In production farms, vaccinate waterfowl ready for foie gras production (ducks and geese), other free-range waterfowl, free-range turkeys, and pre-adult pullets destined for free-range rearing. The objective is to limit the scale of outbreaks by targeting the production sectors where the virus is most likely to be introduced and spread. This scenario requires vaccines to be more widely available than in Scenario 1.

Scenario 3: If sufficient vaccines are available, vaccinate waterfowl raised for meat production, isolated-reared turkeys (in buildings), free-range Galliformes meat chickens other than those listed for Scenario 2, and free-range laying hens.

In turn, IEC and IPC have issued a joint statement to persuade the industry, international organizations, and governments to allow vaccination while reducing the risk of trade barriers.

Ensuring the effectiveness of avian influenza vaccination

The effectiveness of the proposed scenarios will depend on numerous hypotheses and conditions, notes ANSES:

• The epidemiological context in autumn 2023 will be the same as observed today (H5N1 viral strain similar to the one circulating in the 2022-2023 season). • The available vaccine supply will allow vaccination of each species and induce collective immunity. • The vaccination strategy will be in line with the time required to acquire immunity after vaccine administration and the duration of vaccine protection. • The vaccination strategy will be compatible with agricultural practices, particularly in terms of logistics and economics.

The agency also mentioned that if vaccination is implemented, it will require a consolidated surveillance protocol for vaccinated farms "so that those animals that are still infected can be identified and culled as quickly as possible."

Reuters emphasizes that none of the scenarios involve vaccinating broiler chickens, which it says constitute the majority of poultry, and the government tends to at least partially follow ANSES' recommendations.

Damage and Unexplained Consequences

With millions of commercially raised birds affected by avian influenza in thousands of facilities across major poultry-producing countries, the call for vaccination is growing stronger. So much so that the International Egg Commission (IEC) and International Poultry Council (IPC) have issued a joint statement to convince the industry, international organizations, and governments to allow vaccination, while reducing the risk of trade barriers.

Since the beginning of spring 2022, more and more alarm signals have been sounding as the poultry sector and beyond realized that the avian influenza virus was not behaving as expected. Of course, the devastating disease is not new—it is an unfortunate event that repeats annually. "We have already seen a change in disease patterns over the past two years," says veterinary epidemiologist Dr. Arjan Stegeman.

As a member of the International Egg Commission's global expert group on avian influenza, Stegeman has witnessed the disease evolving from a very rare event until 2004 to an annual occurrence since 2014. "Normally, the virus would peak in December and then gradually disappear. In 2022, that did not happen, and the virus remained present throughout the year, even during the summer when we expected it to diminish in dry and warm conditions."

His findings are corroborated by the European Food Safety Authority (EFSA). The European Centre for Disease Prevention and Control and the EU Reference Laboratories reported an unprecedented number of highly pathogenic avian influenza (HPAI) virus variants detected in both wild and domestic birds from June to September in Europe.

In previous years, either no cases were confirmed or only a few during the summer period. The general 2021-2022 HPAI season produced the largest epidemic recorded in Europe thus far. The ongoing HPAI season has been extremely damaging, with a total of 2,467 outbreaks in poultry and 47.5 million birds culled in affected units.

Crossing the Atlantic

Furthermore, the HPAI A(H5N1) virus has crossed the Atlantic Ocean for the first time in the autumn of 2021, spreading from Europe to North America through migration routes, causing a severe epidemic in poultry in several Canadian provinces and US states, affecting 40 million birds and counting.

"It is time to no longer consider avian influenza and vaccination as a taboo and to react with a sense of urgency."

EFSA recommends the rapid implementation of appropriate and sustainable strategies to mitigate HPAI, including adequate biosecurity measures and surveillance strategies for early detection. Medium and long-term prevention strategies should be considered in densely populated areas and in poultry production systems highly susceptible to avian influenza exposure.

"With the virus ubiquitous in wild birds, leading to unique introductions into commercial operations time and time again, the current strategy no longer eliminates the virus. If we do not change how we deal with this disease, the poultry industry is seriously at risk," notes Stegeman.

Avian Influenza Vaccination

Controlling the virus is necessary for several reasons. The most pressing for the poultry industry itself is limiting the direct damages caused by the disease, for business continuity, and, no less importantly, for the support of governments that shoulder part of the burden by compensating for the direct and indirect costs of culling measures.

"But there is more," says Ben Dellaert, President of the IEC Avian Influenza Expert Group. "In the current situation, free-range farming becomes almost impossible from a disease perspective. At the same time, our industry knows that our license to produce – consumer acceptance – requires the use of alternative housing systems.

But with avian influenza, we are in a difficult situation. It will become increasingly challenging to explain to consumers that we produce valuable animal proteins at the expense of millions of birds dying from a disease. This requires new solutions."

As with many poultry diseases, Newcastle disease being just one example, vaccination is the most obvious tool to combat avian influenza. And that is precisely what Dellaert's avian influenza expert group is working on.

"We want to make vaccination possible and acceptable. For this, we have drafted a joint position held by both the International Egg Commission and the International Poultry Council, urging international animal health organizations and all our member nations to persuade national veterinary authorities to approve vaccination."

As Dellaert points out, there are several hurdles before vaccination can be implemented. "Of course, there are technical questions. Which vaccine, for which virus strains? Can we differentiate between vaccinated and infected birds? What guidelines should our avian influenza surveillance program provide?

That being said, technical issues can be overcome as a lot of research is underway. The real challenge to be overcome before moving forward is trade restrictions. If vaccination leads to trade barriers, it will be difficult to implement a new avian influenza strategy for exporting countries."

Trade implications

Bird flu has often been used and misused to close borders for fear of infection and to protect local markets. Despite the fact that the virus has become a global threat to poultry production, these reflexes are still a threat. Vaccination is currently in the toolbox of some non-exporting countries.

Exporting countries are hesitant because of the possible consequences, as Chad Gregory, president of the United Egg Producers of the US, said. "All of our egg producers support a vaccination strategy going forward because they bore the brunt of the flu outbreak. To be honest, layer operations are affected to death in this roulette game.

However, in my opinion, it is highly unlikely that our US poultry producers will see vaccination as an option. Their fear is that they will have a big impact on exports, worth  3-4 billion USD annually. And vaccination is too valuable a tool not to use."

From his European perspective, Stegeman warns that the broiler industry is by no means immune to infection, as farms with traditional production systems (closed houses) have already been hit in Europe. He adds: "Avian flu has to be stopped because there is a public health side to it as well. The current strain of the virus is not dangerous to humans, but we are seeing mutations and have even recently witnessed cross-species infections in mammals."

"Even if we don't have a perfect vaccine, it can still be valuable. Over the years, various animal diseases have been controlled by imperfect vaccines. Newcastle disease, foot-and-mouth disease and Aujeszky's disease are all good examples of this."

Three tests, three vaccines

Before the end of 2022, three research facilities hoped to see the first results of a small-scale vaccine trial. In France, Italy and the Netherlands, several vaccines are being tested indoors to get an idea of how well they protect and whether there is any shedding of the virus. Although promising so far, controlled trials in the field must follow, pushing the horizon for effective vaccination years into the future.

In the Netherlands, a pharmaceutical company is testing vaccines against current H5 viruses in laying hens. "More information is needed about potential avian flu vaccines before they can be applied in the field," explains avian flu researcher Dr. Nancy Beerens in Poultry World's sister publication Boerderij.

The research is carried out under the auspices of the Dutch Ministry of Agriculture, Nature and Food Quality. This first vaccine trial is being conducted in animal units in the high isolation unit of the WBVR.

Modern vaccines have been developed by “different pharmaceutical companies, Ceva (which already has vaccines registered in the US and elsewhere), a new vaccine from Huvepharma, and a third vaccine, also new, which, at the request of the manufacturer WBVR, did not provide any information.

Tested vaccines are based on different technologies. "At this stage we are testing the effect of the vaccines on the clinical signs of the disease. The effectiveness of the vaccines against the spread of the virus is another important parameter in the study," says Beerens. "We expect that the new types of vaccines we are testing in this study will provide better protection against the spread of the virus than previous vaccines."

It is also possible to distinguish between vaccinated and infected animals using specific diagnostic tests. However, several European countries have started vaccination studies. The results of these studies are very important for the future European agricultural policy, which could allow the vaccination of poultry.

Until the vaccine, there's more!

WBVR's avian influenza vaccination research is the first step in research aimed at combating avian influenza through vaccination. The information obtained from this research will be used for future research such as a field study.

Unfortunately, farm birds will not be able to vaccinate against the virus in the short term. "We're not there with just one attempt, even if it's a success," emphasizes Beerens. A field trial is likely to follow in January, which will then last a year to see if the vaccines offer long-term protection and how the vaccination works in day-to-day poultry farming practice.

In addition, new vaccines (including the three in the study) will first need to be registered by the manufacturer for approval. Beerens said it was not possible in practice to vaccinate in the 2022-23 flu season, adding that he doubted everything would be ready to start vaccinating next season (starting in October 2023).

Moving in the right direction, but at a low speed

As for new technology avian flu vaccines, vaccine manufacturer Ceva Animal Health has extensive experience in controlling the disease. Time for Poultry World to sit down with their experts, Sylvain Comte, Christophe Cazaban, Bertrand le Tallec and Mustafa Seçkin Sandikli. Veterinarians are optimistic about the role a vaccine can play in mitigating bird flu damage.

"If last season's bird flu outbreaks taught us one thing, it's that the old elimination solution won't help us anymore," said Comte. He emphasized that this is not just the conclusion of one vaccine manufacturer: "Industry and animal health representatives recently gathered at the HPAI meeting of the International Alliance for Biological Standardization (IABS) in Paris. Here we witnessed an important shift in the discussion of bird flu.

Previously, every conversation about vaccination always ended with someone summarizing the impossibilities due to potential trade restrictions. However, in the recent meeting it was established that the commercial argument is no longer a prerequisite for taking steps forward."

However, even without the fear of trade barriers, experts say there are still many steps ahead. "There are many misconceptions about the old killed vaccines, which we have to take," says Ceva's scientific director, Christophe Cazaban. He continued:

"Our experiences with the vaccine in several countries have taught us that we can protect against several virus strains, reduce shedding and distinguish between vaccinated and infected birds (DIVA). The challenge now is that we are moving from countries with an endemic bird flu situation with low surveillance to a highly controlled region where we have and want to maintain strict surveillance. This requires research, additional assurance and local scientific evidence and documentation. That's what's going on right now."

"It's time to stop considering bird flu and vaccination as a taboo and react with a sense of urgency," says Mustafa Seçkin Sandikli.