New targets identified for a universal influenza B vaccine

A team of Australian researchers, led by The Peter Doherty Institute of Infection and Immunity, have identified fragments from influenza B viruses that the immune system consistently recognise, in a milestone study that offers promising targets for a universal influenza B vaccine.

Influenza B viruses can cause significant illness and mortality, especially in children, yet they remain understudied and little is known about how the immune system interacts with these viruses. Scientists led by Professor Katherine Kedzierska, Head of the Human T cell Laboratory at the Doherty Institute, set out to change this by delving into the intricacies of the immune response to influenza B viruses, publishing their results in the journal Nature Communications.

The team’s study focused on killer T cells, also known as CD8⁺ T cells, which play a crucial role in the antiviral immune response, and discovered how they target influenza B viruses to combat infection. Co-first author Tejas Menon, a graduate researcher at the Doherty Institute, described the challenge of identifying the specific parts of the influenza B viruses that killer T cells bind to as like searching for a needle in a haystack.

“To tackle a virus, killer T cells need to be able to recognise the virus and find the best viral parts to target,” Menon said.

“As new variants of a virus emerge, killer T cells can recognise fragments that are unchanged among those influenza variants. This makes killer T cells an attractive immune population to stimulate with vaccines.

“In the context of influenza B viruses, we were excited to discover nine viral fragments which provoked a strong immune response from killer T cells and remained unchanged in the ‘virus’s history’. This finding, reached after sieving through hundreds of influenza B virus particles … is a significant advancement in our understanding of influenza B immunity.”

Until now, only 18 such viral fragments had been identified, limiting the ability to generate new vaccines against influenza B viruses that prevent severe illness and death. This comprehensive study brings the total to 27, offering more options for vaccine development.

The researchers also explored how this immune response changes with age, providing valuable information for tailoring health strategies for different age groups. Study co-author Dr Carolien van de Sandt, a senior research fellow at the Doherty Institute, said that the work gives valuable insights into age-related immune responses to influenza B viruses.

“As we age, our immune system responds differently to the flu,” van de Sandt said.

“While we detected killer T cells that recognise influenza B viral fragments across the human lifespan, from young children to the elderly, those T cell responses substantially peaked in adults. This may help explain why this particular age group is protected from severe influenza B infections.

“Our findings also showed that killer T cells that recognise influenza B viruses have a very good memory, but are not as numerous in elderly people and children. This is fascinating, as children have a higher burden from influenza B than adults and the elderly.”

Kedzierska said the clinical implications of the study are substantial, with the research presenting the first step towards the development of new T cell-based influenza B vaccines. Current influenza vaccines primarily rely on antibodies that target specific strains, necessitating frequent updates due to mutations in the virus, but T cell-based vaccines have the potential to provide broad immune protection across all variants of influenza B viruses for various age groups.

“The influenza B viral T cell targets that we have found could be included in new T cell-based vaccines, which could significantly reduce severe cases and death caused by influenza B, especially in children, and alleviate the burden of seasonal influenza epidemics,” Kedzierska said.

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