Investigating the Antigenic Evolution of Influenza B Viruses and RSV
In a world where viruses are in a constant state of evolution, with new ones frequently emerging, two pivotal terms come to the forefront: genetic and antigenic evolution. During the parallel session on Epidemiology and (Sero)Surveillance, including Virus Evolution and Strain Selection, three talks addressed this topic.
Unravelling the Genetic and Antigenic Evolution of Influenza B Viruses
Thi Hoai Thu Do and Lara Schwab, both from the University of Melbourne, Australia, are researching the antigenic drift of the hemagglutinin (HA) and neuraminidase (NA) of influenza B viruses (IBVs) using antigenic cartography. Antigenic characteristics of viruses are measured using ferret antisera to compute antigenic maps. These maps visualise and quantify the antigenic relationships between various viruses. Thi Hoai Thu Do was able to observe antigenic drift of IBV NA into three clear distinct antigenic clusters. Intriguingly, these clusters did not align with the three known HA antigenic lineages. In the future the number of viruses included in the antigenic map will be expanded in the hope that these initial findings can be validated and further expanded. Overall, these results highlight that the HA and NA evolution of IBVs is discordant and, therefore, the addition of NA in an influenza virus vaccine might provide additional protection against IBV isolates that have genetically drifted in the HA.
Lara Schwab's research focuses on unravelling the genetic and antigenic evolution of the HA of IBVs over an impressive timespan of 81 years. Schwab emphasises a crucial point: “A genetic mutation does not necessarily change antigenic properties”. Antigenic properties here refer to the way that antibodies recognize the virus. She identified that the B/Yamagata lineage diverged from the B/Victoria lineage 43 years ago. By combining the amino acid sequence and antigenic data, Schwab discovered position 165 of the viral HA as a key site for the 2004-2008 cluster transition between B/Malaysia/2506/2004 and B/Brisbane/60/2008. Furthermore, position 150 was identified as a key mutational site between Ancestral and B/Victoria viruses. The assessment of additional amino acid mutations in recent clusters is ongoing and will be eagerly awaited.
Exploring the Mutational Hotspots in the RSV-F Protein
Joining Thi Hoai Thu Do and Lara Schwab in the pursuit of studying virus evolution is Lucy Mosscrop from Imperial College London, United Kingdom, whose focus lies on the RSV-F protein. Given that RSV is, just like influenza, an RNA virus and thus prone for acquiring mutations, she tries to discover mutational hotspots in the antibody binding sites of the relatively well conserved F-protein, and identify the functional consequences. By analysing a total of 1,018 whole genome sequences, several known resistance mutations and some novel mutations in binding sites for Nirsevimab and Clesrovimab were identified. These mutations occurred in a low frequency, highlighting that RSV’s antigenic escape might not be on the immediate horizon.
As these researchers continue to unravel the intricate antigenic evolution of respiratory viruses and associated driver mutations, their work holds the promise of paving the way for more effective prevention and treatment strategies.
