Complete mapping of viral escape from neutralizing antibodies
#MMPMID28288189
Doud MB
; Hensley SE
; Bloom JD
PLoS Pathog
2017[Mar]; 13
(3
): e1006271
PMID28288189
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Identifying viral mutations that confer escape from antibodies is crucial for
understanding the interplay between immunity and viral evolution. We describe a
high-throughput approach to quantify the selection that monoclonal antibodies
exert on all single amino-acid mutations to a viral protein. This approach,
mutational antigenic profiling, involves creating all replication-competent
protein variants of a virus, selecting with antibody, and using deep sequencing
to identify enriched mutations. We use mutational antigenic profiling to
comprehensively identify mutations that enable influenza virus to escape four
monoclonal antibodies targeting hemagglutinin, and validate key findings with
neutralization assays. We find remarkable mutation-level idiosyncrasy in antibody
escape: for instance, at a single residue targeted by two antibodies, some
mutations escape both antibodies while other mutations escape only one or the
other. Because mutational antigenic profiling rapidly maps all mutations selected
by an antibody, it is useful for elucidating immune specificities and
interpreting the antigenic consequences of viral genetic variation.
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