Park JK, Xiao Y, Ramuta MD, et al. Pre-existing Immunity to Influenza Virus Hemagglutinin Stalk Might Drive Selection for Antibody-Escape Mutant Viruses in a Human Challenge Model. Nat Med. 2020;10.1038/s41591-020-0937-x
The conserved region of influenza hemagglutinin (HA) stalk (or stem) has gained attention as a potent target for universal influenza vaccines1-5. Although the HA stalk region is relatively well conserved, the evolutionarily dynamic nature of influenza viruses6 raises concerns about the possible emergence of viruses carrying stalk escape mutation(s) under sufficient immune pressure. Here we show that immune pressure on the HA stalk can lead to expansion of escape mutant viruses in study participants challenged with a 2009 H1N1 pandemic influenza virus inoculum containing an A388V polymorphism in the HA stalk (45% wild type and 55% mutant). High level of stalk antibody titers was associated with the selection of the mutant virus both in humans and in vitro. Although the mutant virus showed slightly decreased replication in mice, it was not observed in cell culture, ferrets or human challenge participants. The A388V mutation conferred resistance to some of the potent HA stalk broadly neutralizing monoclonal antibodies (bNAbs). Co-culture of wild-type and mutant viruses in the presence of either a bNAb or human serum resulted in rapid expansion of the mutant. These data shed light on a potential obstacle for the success of HA-stalk-targeting universal influenza vaccines-viral escape from vaccine-induced stalk immunity.
See Also:
Latest articles in those days:
- Epidemiological characteristics of human infections with avian influenza A(H5N6) virus, China and Laos: A multiple case descriptive analysis, February 2014-June 2023 2 hours ago
- Interim Estimates of 2023-2024 Seasonal Influenza Vaccine Effectiveness Among Adults in Korea 11 hours ago
- Abundant Intra-Subtype Reassortment Revealed in H13N8 Influenza Viruses 2 days ago
- Locations and structures of influenza A virus packaging-associated signals and other functional elements via an in silico pipeline for predicting constrained features in RNA viruses 2 days ago
- Molecular Characterization of Non-H5 and Non-H7 Avian Influenza Viruses from Non-Mallard Migratory Waterbirds of the North American Flyways, 2006~2011 2 days ago
[Go Top] [Close Window]