Published on 26 November 2024

Blog Robin Avanthay – Influenza

«The goal was to develop a novel mucosal vaccine against influenza A virus and assess its efficacity in the pig model».

Virus Influenza A : How a novel vaccine platform could help to limit virus infection and transmission in pigs and humans

Influenza or «flu» is a seasonal disease caused by the influenza virus, especially type A viruses. The World Health Organization (WHO) estimates that over a billion people contract the disease each season, leading to around 650,000 deaths. Wild birds, and specifically waterfowl, are known to be a natural reservoir of influenza A viruses, but other species can also become infected may serve as intermediate hosts. This is the case with pigs, which serve as hosts for swine, avian and human influenza viruses and, following adaptation and exchange of gene segments, can be the source of new influenza A viruses with pandemic potential. Vaccination of both pigs and humans can limit the severity of the symptoms and the spread of the virus.

Due to the role of domestic pigs as an intermediate host in the evolution of pandemic influenza A viruses, the IVI is working on the development of nasally administered vaccines to induce an immune response in the mucosal tissue of the upper respiratory tract which may prevent transmission of the virus from one animal to another.

Interview with Dr Robin Avanthay

• What was the aim of your doctoral thesis?

  The goal was to develop a novel mucosal vaccine against influenza A virus (IAV) and assess its efficacity in the pig model.

• What are the main findings of your dissertation?

  Throughout my thesis, with the combined efforts of Artur Summerfield and Obdulio Garcia-Nicolas from the Immunology department and Gert Zimmer from the Virology department, we identified a live-attenuated influenza vaccine (LAIV) candidate encoding modified viral proteins (NS1 and PA-X) that are involved in shut-off of the host response. By using a novel bronchiolar epithelial cell line, we showed that this vaccine candidate is attenuated due to an increased innate immune response by the infected cells and reduced virus-induced cell death, leading to impaired release of new viral particles (Link to the publication). However, intranasal immunization of this LAIV in the pig model revealed that it replicated for too long time to be considered as safe. We therefore developed a novel vaccination protocol consisting of an initial intramuscular immunization using a non-spreading vector expressing the hemagglutinin antigen of IAV, followed by an intranasal boost using the LAIV. We showed that this protocol considerably increased the safety of the vaccine by reducing LAIV replication and inducing a robust systemic and local immune response, providing sterile immunity upon homologous challenge infection.

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

  The elimination of IAV before it starts replicating in the host (sterile immunity) is the only way to prevent initial infection and transmission of IAV, subsequently limiting the probability of pandemics. The vaccine we developed allowed such sterile immunity to be achieved in pigs and is therefore a promising approach that should be further investigated for possible translation to humans.

• What are you most proud of in this work?

  Overall, I am delighted with how the project turned out. As I was part of two teams (the groups led by Artur Summerfield and Gert Zimmer), the suggestions as to how the project should continue were sometimes a bit divergent and I am happy with how we dealt with that to keep everything on track.

• What did you especially like about working on your thesis?

  The interactions with the rest of the IVI staff and the good atmosphere inside the lab. And the fact that the institute is located in the middle of the countryside was really nice because of all the wild animals running around.

• What was your time at the IVI like?

  I really enjoyed my time at the IVI. Everybody is really friendly and helpful. I would do it all over again.

• What projects do you have coming up, what are your plans?

  I will start working for a company focusing on the development of solid tumor treatments.