Teshome, you’ve been researching avian influenza for more than two decades. What is so special about this disease?
Teshome: Avian influenza is special in many ways. First, there are many different versions of avian influenza, and we see a constant genetic drift and shift which results in new strains of the virus. So basically, nature feeds us new viruses all the time. These new viruses spread amongst aquatic and wild birds, and due to the movement of these animals the disease spreads globally. Avian influenza, or bird flu, can infect a broad variety of mammals, such as cats, minks or seals. This multiplies the spread of the virus. 

You just mentioned that avian influenza has been spreading across the globe. But why is the situation today different from the past?
Teshome: In the past, we had an outbreak, it died out and the same thing happened the next season. Nowadays, the virus stays, particularly clades derived from the highly pathogenic avian influenza viruses of the A/goose/Guangdong/1/1996 lineage H5 continue to have a devastating effect on domestic and wild birds. Especially in Europe, it is becoming a year-round occurrence. There are different explanations for that: Some genetic mutations have increased the viruses' ability to replicate, making them spread more efficiently than before. Or the mutations have also enabled the virus to infect a wider range of bird species compared to previous strains. As a result, the virus can now be transmitted and maintained by more species, leading to a longer duration of infection.

The strains of the avian influenza viruses are classified into two categories – low pathogenic avian influenza (LPAI) and highly pathogenic avian influenza (HPAI). Do we only need to focus on highly pathogenic avian influenza?
Teshome: The short answer is no. Both are important in the overall picture of avian influenza control. Low pathogenic strains result in a mild infection compared to a very high morbidity caused by highly pathogenic avian influenza. However, some low pathogenic subtypes like H9N2 can cause significant losses to the poultry industry through dropping egg production or low hatchability. And some genetic segments of the low pathogenic avian influenza may also lead to the generation of new highly pathogenic strains. 

Any disease outbreak is devastating for the poultry producers which leads to the next question: How can outbreaks of avian influenza be prevented? 
Teshome: Strict biosecurity measures and good hygiene practices are essential to prevent avian influenza outbreaks. However, relying solely on those measures is no longer sufficient to prevent an outbreak, as the disease has become endemic in many regions. This situation requires the implementation of additional control measures, such as vaccination. Several countries are interested and willing to consider vaccination as an additional measure to prevent avian influenza.

How does vaccination help limit the impact of avian influenza?
Teshome: We need to take a holistic approach and follow a comprehensive disease control strategy. Vaccination alone is not enough. Biosecurity measures are essential, this includes control in movement of birds and keeping wild birds and rodents away from poultry farms. In addition to those, we can vaccinate the poultry flocks. Vaccination not only helps block the transmission of the virus, but also reduce the size of the outbreak and limit the impact on animal welfare and sustainability. 

Once a bird has been infected with avian influenza, is it possible to treat the disease?
Teshome: Highly pathogenic avian influenza is a severe viral disease and there is no treatment available. In humans, antivirals can be used, but they are usually not an option in chickens. So, there is no treatment available, once the birds start showing clinical signs. 

What we learnt while dealing with avian influenza for a while now is that there are many subtypes and constantly evolving virus strains and clades. What does this mean for current vaccines and vaccine development?
Teshome: An influenza strain is a genetic variant or subtype of the influenza virus. An influenza clade or group is a subdivision of influenza viruses, beyond subtypes or lineages, based on the similarity of their haemagglutinin gene sequences. One way flu viruses change is called “antigenic drift.” Drift consists of small changes or mutations in the genes of influenza viruses that can lead to changes in the surface proteins of the virus. Another type of change is called “antigenic shift.” A shift is an abrupt, major change in a virus, resulting in new viruses that may infect humans or other animals. Therefore, the biggest challenge in vaccine development is the constant genetic change resulting from antigenic drift or shift. For this reason, the holy grail of avian influenza vaccinology is developing a “universal vaccine” that helps against a wide range of virus subtypes and strains. Innovative strategies and the use of improved vaccine platforms are currently being explored.

The situation with avian influenza differs from region to region. France is now starting a vaccination campaign with our VOLVAC B.E.S.T. AI+ND vaccine as the first country in Europe. Do other European countries test our vaccines as well? What about countries outside Europe?
Teshome: Within Europe, the Netherlands has just started a controlled field study test with our vaccines in chickens. The set-up of the experiment is quite interesting: They have a group of animals that receive our Vaxxitek H5 and another group that will first receive our Vaxxitek H5 and then three months later a booster dose of the Volvac B.E.S.T. AI+ND to analyze whether that will show a superior protection or important advantage. This is also very useful data for us to see how long-lived birds can better be protected. Italy is another country that is currently testing our vaccines in turkeys in different conditions. Outside Europe, the United States is currently testing our vaccines.  

Avian influenza is a zoonotic disease, meaning that it can also infect mammals, such as pigs, cats, dogs, and even humans. How often do these infections occur and how severe can they be? 
Teshome: We are seeing a rising concern among authorities across the globe. The good thing is that most of the influenza viruses circulating in birds are not zoonotic. However, we have some HPAI strains that can infect a variety of other mammals, including humans, which can pose a threat to the public. Now as the disease becomes more and more endemic, the exposure to various species increases. One of the scenarios is that the virus might adapt and trigger a pandemic, though now, we are not seeing many human infections.

How optimistic are you that the number of large outbreaks will decrease in the coming years?
Teshome: Whether we like it or not, avian influenza is going to stay with us. I look into the future quite optimistically, because with vaccination we now have an additional control measure. This will not only have a positive impact on mortality rates, but also reduce the size of the outbreaks, because they block transmission. Additionally, the openness towards vaccination stimulates further research in this area. Governments, authorities, and companies will invest in further innovation to find more effective and more broad-spectrum vaccines.

Teshome Mebatsion is a veterinarian and holds a Ph.D. in Molecular Virology from the University of Giessen, Germany. He is currently working for Boehringer Ingelheim as Head of Viral Diseases Research Animal Health within Global Innovation. His career encompasses academic and commercial spheres with over 25 years of experience in animal health vaccine research. He is a recognized leader in the field of recombinant vaccine technology with translational research leading to CVB (USDA) or EMA licensed animal health vaccine products, numerous peer-reviewed scientific publications and more than a dozen patents.