Published on 28 May 2025

Marion Stettler’s blog – Avian influenza

“We have successfully tested an avian influenza vaccine in 24 different bird species at Bern Animal Park and Basel Zoo”

Use of a vector vaccine against H5N1 avian influenza in zoo birds – a successful veterinary doctoral thesis

Avian influenza caused by highly pathogenic avian influenza viruses (HPAIV) of the H5N1 subtype has killed millions of wild birds and domestic poultry in recent years. This has had not only significant economic consequences but also far-reaching effects on species conservation. In a local example dating from 2022, Bern Animal Park recorded a fatal case of H5N1 in its pelican enclosure on the Aare river. The Dalmatian pelican involved was thought to have been infected by a free-living grey heron. Due to the tense epidemiological situation, all zoo birds had to be kept in avian influenza-proof housing in both 2022 and 2023. However, various bird species show increased susceptibility to stress- and husbandry-related diseases when kept in confinement for extended periods. The associated restrictions significantly impair animal welfare and render it impossible to keep many species under species-appropriate conditions in the long term.

This is a problem not only in terms of animal welfare but also because it poses a risk for conservation, especially in the case of endangered species.

Interview with Marion Stettler

• What was the aim of your dissertation?

  To protect birds against this highly contagious disease in future and to avoid the adverse effects associated with long-term confinement, a joint vaccination project was launched involving Bern Animal Park, Basel Zoo and the Institute of Virology and Immunology (IVI). The vaccine used in this study was developed at the IVI and is based on vesicular stomatitis virus (VSV), a virus that does not occur naturally in birds. To create the vaccine, the original surface protein of VSV – the “G protein” – was removed and replaced by the H5 protein of avian influenza virus. Thanks to this targeted adaptation, the vaccine (called VSVΔG(H5)) is directly aimed at the avian influenza virus currently in circulation and is also no longer capable of replication, guaranteeing excellent safety.
  
  The project set out to understand whether vaccination confers effective protection against HPAI H5N1 under natural conditions in different bird species, whether there are any species-specific differences in the strength and duration of the antibody response to the HA antigen, whether any adverse effects occur following vaccination and whether the vaccine is excreted into the environment.

• What are the main findings of your dissertation?

  A total of 317 birds from 24 different species were immunised intramuscularly at three time points. Over a 400-day period, we collected multiple blood samples for analysis in order to study the immune response.
  
  The study results are very promising: vaccinated birds showed high concentrations of H5Nx-neutralising antibodies. A year after the first vaccination, we were still detecting high levels of neutralising antibodies, indicating long-lasting immunity. No vaccine-related adverse effects were observed and analysis of water and faecal samples showed no excretion of the vaccine into the environment. Finally, the vaccine also enabled us to differentiate vaccinated animals from infected animals using a simple serological test (DIVA).
  
  To sum up, VSVΔG(H5) is a very safe and effective DIVA vaccine for protecting various bird species against highly pathogenic H5N1 influenza viruses. This vaccine could therefore become an effective weapon in combating the current H5N1 panzootic.
  
  Interestingly, we detected antibodies not only after vaccination; we also found antibodies against avian influenza viruses in some birds even before the first vaccination. This was particularly pronounced in the flamingos, indicating prior or possibly ongoing contact with these viruses and raising the question of how widespread such antibodies are in other flamingo flocks in Switzerland. We therefore launched a second project in which we are testing sera from flamingos from five Swiss zoos for antibodies against various influenza subtypes. Initial results show that such antibodies are present in each flock, although with varying degrees of prevalence. We are still evaluating this follow-up project but we plan to publish the data at a later stage and hope our findings can help to improve the protection of these animals in the future.

• To what extent will your findings help to advance research?

  We have successfully tested a vaccine against H5N1 avian influenza in 24 different bird species. However, the vaccine vector used in this case can also be used for the development of similar vaccines. What is crucial now is that the project should not end here. At present we are actively seeking investors to progress the licensing of the vaccine..

• What aspect of this work are you especially proud of?

  I am especially proud of how well the project went and of playing an active part in it. It is an excellent example of successful cooperation between different institutions – the IVI, Bern Animal Park and Basel Zoo. As a doctoral student, I was working actively at all three institutions so could act as a link between them and the local teams on the ground. The project demanded huge effort in terms of organisation, but the results made that effort worthwhile. I would like to thank everyone involved – without commitment all-round, we could never have completed this project in this form.

• What did you especially like about your dissertation?

  While writing it, besides working on the project and analysing samples in the lab, I also worked as an assistant veterinarian at Bern Animal Park. I really enjoyed having that variety. It was also challenging, of course, to combine both areas and maintain an overview. But that’s precisely what made the time so exciting: I learned an incredible amount, gained valuable insights I’d probably never have had otherwise, and also met some wonderful people from a wide range of disciplines!
  
  And last but not least: we hope to be able to use the knowledge we have gained to make a valuable contribution to protecting these animals in the future.

• How was your time at the IVI?

  At first it was challenging to find my feet as I had little experience of lab work, coming from the field of veterinary medicine. But during my time at the IVI I had the opportunity to meet many dedicated and talented people who supported me enormously. I was able to talk to the researchers in depth about their projects, and our conversations and discussions were always stimulating and informative, yielding new ideas for my own project.

• What are your plans now, what are you going to do next?

  My dissertation has already given me valuable insights into zoo and wild animal medicine, which has always fascinated me due to its diversity and the associated variety and challenges. I would like to continue training in this direction and expand my knowledge and skills. Although my actual path remains undecided, the direction is clear.

Publication
Preprint - bioRxiv. Jan. 2025
Immunization with a novel RNA replicon vaccine confers long-lasting protection against H5N1 avian influenza virus in 24 bird species 

Authors
Stettler M, Hoby S, Wenker C, Wyss F, Heiderich E, Butticaz L, Ruggli N, Darpel K, Zimmer G.

Project information
Research project: vaccination of zoo birds against highly pathogenic avian influenza