Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin

By Juhye M. Lee, Rachel T. Eguia, Seth J. Zost, Saket Kumar Choudhary, P. Wilson, Trevor Bedford, Terry L. Stevens-Ayers, M. Boeckh, A. Hurt, S. Lakdawala and 2 more. 2019

97 citations recorded by the source corpus.

A longstanding question is how influenza evolves to escape human immunity, which is polyclonal and can target many distinct epitopes on the virus. Here we map how all amino-acid mutations to influenza’s major surface protein affect viral neutralization by polyclonal human sera. The serum of some individuals is so focused that it selects single mutations that reduce viral neutralization by over an order of magnitude. However, different viral mutations escape the sera of different individuals. This individual-to-individual variation in viral escape mutations is not present among ferrets, which are frequently used as a model in influenza studies. Our results show how different single mutations help influenza escape the immunity of different members of the human population, a phenomenon that could shape viral evolution and disease susceptibility.

Subfields: Epidemiology, Molecular Biology

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Citations in the corpus

Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, positive): “Such polyclonal responses targeting multiple distinct epitopes might explain the magnitude of neutralization observed and should minimize the risk of selection or emergence of escape mutations (Davis et al., 2018; Lee et al., 2019).”
Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding (2020, unknown): “It should be possible to shed further experimental light on the potential for antigenic drift by extending our deep mutational scanning methodology to directly map immune-escape mutations as has been done for other viruses (Dingens et al., 2019; Lee et al., 2019; Wu et al., 2019).”
Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding (2020, unknown): “It should be possible to shed further experimental light on the potential for antigenic drift by extending our deep mutational scanning methodology to directly map immuneescape mutations as has been done for other viruses (Dingens et al., 2019; Lee et al., 2019; Wu et al., 2020a).”
Comprehensive mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human serum antibodies (2021, background): “One reason that influenza virus undergoes such rapid antigenic evolution is that neutralizing human immunity often focuses on just a few residues in hemagglutinin, such that a single mutation can dramatically reduce neutralization (Lee et al., 2019).”
Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition (2020, unknown): “Others, such as influenza virus, undergo rapid antigenic drift, such that immunity elicited against one viral strain can be ineffective against that strain’s descendents just a few years later (Lee et al., 2019; Smith et al., 2004) .”