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21 Mar 2022

Researchers uncover how the immune systems works to target influenza B virus in Indigenous populations, potentially leading to hopes for universal, broad reaching flu vaccine

Researchers at the Doherty Institute have uncovered a new way the immune system works to target influenza B virus infections, taking a step closer to a universal flu vaccine.

Influenza infections continue to cause significant morbidity and mortality, particularly in Indigenous Australian populations, despite the availability of vaccines and anti-viral therapies.

A major hindrance to long-term vaccine effectiveness is the way that the virus mutates, making annual re-formulation of the vaccine a requirement to maintain immunity, although complete protection is not guaranteed.

Lead author on the paper University of Melbourne PhD Candidate Jennifer Habel, a member of the Kedzierska Laboratory at the Doherty Institute, explains that the failure of traditional flu vaccines to provide broad immunity against multiple influenza strains is due the fact these vaccines target viral surface proteins.

“Our research is focusing instead on cellular immunity, in particular CD8+ T cells, which have been proven to play a vital role in clearing influenza virus infection,” Ms Habel said.

“More importantly, CD8+ T cells can target conserved viral regions of influenza, which do not shift and flow in the same way as the surface viral proteins which traditional vaccines target.”

CD8+ T cells work to kill virally infected cells by recognising certain viral peptides presented by human leukocyte antigens (HLA), molecules found on the surface of most cells in the body.   

“When a peptide and HLA interact in a way that is recognised by the CD8+ T cells, we call this an epitope,” Ms Habel explained.

“If we find an epitope, we can use this peptide to formulate a vaccine which elicits this response and effectively primes the immune system.

Published in PLoS Pathogen, the research looked at one of the most prevalent human HLAs, A*11:01, and discovered the first epitope for influenza B viruses.

This A*11:01 HLA is also highly expressed in Indigenous Australians.

University of Melbourne Professor Katherine Kedzierska, a Laboratory Head at the Doherty Institute and Ms Habel’s supervisor, said this discovery is part of a bigger project her team is working on in trying to create a universal flu vaccine for Indigenous Australians.

“We want to be able to identify peptides that stimulate a CD8+ T cell response in the five most common HLAs in Indigenous Australians,” Professor Kedzierska explained.

“We will then be able to use these peptides to formulate a vaccine that that can provide effective protection from a wide range of influenza strains.”