Dr Marios Koutsakos is a postdoctoral research fellow at the Peter Doherty Institute for Infection and Immunity, University of Melbourne. He works on the development of a universal influenza B vaccine and on understanding the fundamental biology of immune responses to vaccination. Dr Koutsakos received the 2020 NHMRC Frank Fenner Investigator Grant Award.
In 1940, a new virus was isolated from the respiratory tract of children. This virus had somewhat different characteristics to the recently isolated influenza A viruses (IAV) causing similar disease and was named influenza B virus (IBV).
IBVs circulate annually during seasonal epidemics and typically account for one quarter of annual influenza cases. However, in some years IBVs can account for more than 80 per cent of influenza cases and can cause significantly severe disease in younger populations. Indeed, up to 52 per cent of influenza-related paediatric deaths can be attributed to IBV.
Despite the considerable health and subsequent socio-economic burden of IBV, research has primarily focused on IAV, leaving IBV overlooked. This is mostly a result of the lack of animal reservoirs for IBV, in contrast to IAVs, which have reservoirs in a large number of animal species. Animal-derived IAV strains that acquire the ability to efficiently transmit from human to human, and to which humans have little immunity against, can cause devastating pandemics. Because IBVs do not have established animal reservoirs, and therefore cannot cause pandemics, they have been overlooked.
This lack of animal reservoirs, however, may potentially make IBVs vulnerable to elimination. That would require high levels of immunisation with vaccines that induce broadly protective and long-lasting immune responses and that can be administered to all age groups. However, such a vaccine is currently not available.
Current influenza vaccines can be trivalent (including 2 IAV strains and 1 IBV strain) or quadrivalent (2 IAV and 2 IBV strains). However, they are on average only 50 per cent effective. Additionally, these vaccines need to be updated every year to account for the emergence of new influenza strains that are not covered by the contemporary vaccine composition. This is a laborious and costly process that occurs twice every year, once for each hemisphere. Therefore, although these vaccines are currently our best line of defence against influenza viruses, research is needed to improve the efficacy of influenza vaccines and reduce the impact of influenza viruses, including IBV.
Our research is focused on understanding how IBVs evolve over time to evade the immune system. By gaining a thorough understanding of viral evolution at the molecular level, we hope to rationally design vaccines that provide universal protection against multiple strains of IBV and may not require annual reformulation. Understanding how viruses evolve over time under immune pressure and how to vaccinate against such viruses could be of benefit in our efforts to reduce the impact of other ever-changing viruses like IAV and SARS-CoV-2.
We are further working to understand how IBVs replicate inside human cells to identify steps of the viral life cycle that may be vulnerable to inhibition. This could allow for the development of novel therapeutics or new ways to weaken the virus and generated efficacious and safe live-attenuated vaccine platforms.
I was very honoured to receive the Frank Fenner Investigator award in recognition and in support of my research on influenza B viruses. I am grateful to my mentors, colleagues and collaborators, who have been instrumental in facilitating this research.