T-cell immunity against influenza and SARS-CoV-2 in the ferret model: Towards universal vaccines

Abstract

Influenza viruses are still a major problem. Vaccines are available, but current influenza vaccines only protect against specific virus strains. This protection is insufficient when the virus mutates or when new flu viruses are transferred from animals to humans. It is therefore necessary to develop better influenza vaccines. Preferably, these vaccines offer protection against all influenza viruses – also known as 'universal' vaccines.

Ideally, a universal influenza vaccine should induce T-cell immunity. T cells can protect against influenza by killing infected cells. The advantage of T cells is that they can recognize the more stable pieces of proteins from influenza viruses. These stable pieces do not mutate as quickly and are found in all influenza viruses. As a result, influenza vaccines that induce T-cell immunity could theoretically protect against all influenza viruses.

In this thesis we use the ferret as an animal model to show that T cells can protect against the flu. Ferrets that become infected with one type of influenza virus develop T cells that protect against other influenza viruses. Moreover, this T-cell immunity could be improved by vaccinating ferrets with a new mRNA influenza vaccine directed against the stable virus proteins. This made ferrets less sick after being infected with a new influenza virus. Our research shows that T cells can contribute to the broad protection against influenza viruses. Especially T cells residing in the airways seem to be important for this. We therefore recommend using the power of T cells for the development of new influenza vaccines.