Wageningen World: Bird Flu Vaccines Are Put To The Test

Until recently, vaccination against bird flu was not permitted in Europe, but with new EU rules and favourable research results, vaccinating poultry is now becoming a serious option. Wageningen Bioveterinary Research is studying how effectively bird flu vaccines protect chickens.

The animal ambulances in the Netherlands can barely keep up with the reports they are getting of sick birds and carcasses that need removing. This spring, a particularly large number of black-headed gulls are being found dead; last year, the bird flu virus decimated entire breeding colonies of great terns. Both blackheaded gulls and terns live in colonies and build their nests close together, which enables the virus to spread at lightning speed. Infection spells the end for many wild birds, as neurological damage eventually leads to death.

The avian flu virus is conquering the world. For a long time, South America was spared, but even there, the highly pathogenic H5N1 virus has killed thousands of birds and even sea lions in the past six months. The virus can spread quite easily between different bird species as well as to other animal groups. In Europe, otters, foxes and seals have already died of the virus. For this reason, gloves and protective clothing are worn for handling and disposing of dead birds.

Outdoor Ban
Many bird species found in the Netherlands such as geese, ducks and terns hibernate or breed elsewhere and can pick up an infection there or during migration. That means the virus can reach the country during the au[1]tumn migration and then infect poultry. For this reason, it is compulsory to keep poultry indoors and to shield birds in locations such as zoos. An outbreak of bird flu among poultry automatically means a cull by the Dutch Food and Consumer Product Safety Authority (NVWA). Between October 2022 and April 2023, hundreds of thousands of chickens, turkeys and ducks were culled on more than 20 farms. In 2022, the losses due to culling came to about 44 million euros.

In view of the impossibility of preventing all infections by keeping poultry indoors, and continued presence of the virus among wild birds, there has been a growing interest in recent years in the option of vaccinating poultry against bird flu. With a new generation of vaccines, it is now possible to distinguish between vaccinated birds and those infected with bird flu using a laboratory test. This procedure (known as ‘DIVA’ – Differentiating Infected from Vaccinated Animals) is a key prerequisite for controls in international trade. So the new vaccines remove a major objection to vaccination. Veterinarian and veterinary microbiologist Evelien Germeraad of Wageningen Bioveterinary Research in Lelystad recently conducted research on four bird flu vaccines. She talks here about the vaccination options.

Why is there no vaccination against bird flu in the Netherlands yet?
Throughout Europe, Avian flu is now present year-round in the wild bird population, posing a continuous threat to poultry farmers. They now have to keep their flocks indoors as no other measures against the virus are available yet. Until recently, vaccination against bird flu was not allowed in the EU. In March 2023, European legislation was amended so that vaccination is now allowed if certain conditions are met, such as the use of DIVA vaccines.’

What do these rules mean for poultry farmers who would like to vaccinate in future?
‘The crucial thing is surveillance: you must continue to closely monitor the farm where vaccination has been carried out. The reason for this is that you don’t want the bird flu virus to spread undetected. Because after vaccinating a flock, there is a risk that you won’t see any signs of disease even though the animals are actually undergoing a mild infection. Without vaccination, you notice straightaway if chickens are infected with bird flu, alerted by their symptoms, reduced feed consumption and deaths. As soon as a farmer sees these things, he must report it to the NVWA and they start testing.’

So vaccination cannot completely block the bird flu virus?
‘You can achieve two things by vaccinating against bird flu. Firstly, you inhibit the spread of the virus. Since the Covid-19 pandemic, everyone knows that it helps if vaccination reduces the number of virus particles you spread and therefore your risk of infecting others. Secondly, by vaccinating them, you can ensure that animals that get infected won’t fall ill or die. But that advantage also makes you less likely to notice virus infections. So you have to keep on checking whether the virus is circulating: a vet should visit regularly and animals that die should be checked for the virus.’

You tested several bird flu vaccines recently. What did you want to find out?
‘We selected four vaccines that are at an advanced stage of development, or have already been registered. And some are already in use outside Europe. The aim of our experiment was to see whether they are effective against the H5N1 virus that has been causing outbreaks in recent years, as we didn’t know that yet. And for most vaccines, not enough research had been done on how they affect the spread of the virus, i.e. the effect on virus transmission between vaccinated birds in the same coop.’

How do you find out which vaccines work best?
‘We drew up a number of requirements beforehand. The main requirement is that after vaccination, the reproduction number, the R value, should be below 1, which is a measure of the inhibition of the spread of the virus. Without vaccination, the reproduction number for bird flu in our experiment was higher than 1. As well as that, you want vaccination to provide protection against symptoms and to reduce or prevent mortality in animals that pick up an infection. Also, you need to be able to distinguish vaccinated chickens from unvaccinated chickens with avian flu using a test. If a vaccine meets all these criteria, we pronounce it effective.’

How does this kind of vaccine experiment work?
‘In our trials, five vaccinated chickens were infected with the H5N1 bird flu virus, and were then placed in a coop with five more vaccinated chickens. In the subsequent weeks, we monitored the number of virus particles in the chicken’s throat and cloaca. With that data, you can track the development and spread of the virus, and calculate the R value. The two HVT-H5 vaccines turned out to work the most efficiently, with an estimated R value of under 1. None of the animals that had those vaccines developed symptoms after they were infected.’

How are these types of vaccines administered?
‘Vaccinating against bird flu can be done both in the egg and just after hatching. The least labour-intensive method is to inject the vaccine into a fertilized egg, and that is how it is currently done. There are vaccinations against other viruses and bacteria too. Vaccination against the virus causing Newcastle Disease, for example, is compulsory. The poultry sector already has a lot of the knowledge and infrastructure it needs for vaccination.’

Do these avian flu vaccines also work in turkeys and ducks?
‘That will have to be studied separately. More than 90 per cent of Dutch poultry birds are laying hens and broilers. Other European countries have much larger turkey or duck sectors, so they do research on those birds. Later on, the results of the studies on other poultry species and breeds will be of use here too.’

How long does an avian flu vaccine provide protection; will boosters be needed?
‘That is one of the things we want to look at in a follow-up study. That trial will run for longer, to see if the protection lasts beyond eight weeks. Broilers only live for six to eight weeks, but layers live much longer. There are some indications that these avian flu vaccines provide longer-term protection too, because they not only generate antibodies but also stimulate the T-cells of the immune system, so that it recognizes the virus again later. We’re going to do further research on that.’

Will a new vaccine be needed if a new virus variant emerges?
‘These bird flu vaccines were developed by pharmaceutical companies with the aim of providing broad protection. If an H5N1 virus mutates in a few places around the world, it shouldn’t make much difference. But if, say, an H7 virus emerges a year from now, as happened in 2003, the current H5 vaccines won’t offer as much protection against it. But it’s been H5 viruses that we’ve been dealing with since 2014, and that’s also the variant we have found most often in wild birds in recent years.’

Do we have enough knowledge now to make a decision about bird flu vaccination in the Netherlands?
‘Our study was small-scale and was conducted under laboratory conditions. In the follow-up study, chickens will be vaccinated on a pilot farm, just as is usually done with other vaccines. We want to examine some of those vaccinated chickens in the laboratory in Lelystad at different moments to analyse how well they are protected. That way you can see whether the vaccine is just as effective under everyday conditions. That project will take quite a long time because we also want to study the long-term protection offered by the vaccine.

‘We will pass our results on to the Ministry of Agriculture, Nature and Food Quality, which will develop policy in consultation with the poultry industry. Will bird flu vaccination soon become compulsory? Will it be the farmer’s choice, or a regional decision? These are questions that policymakers have yet to answer.’