# Comprehensive antigenic mapping of seasonal influenza viruses

> **NIH NIH F30** · UNIVERSITY OF WASHINGTON · 2020 · $49,465

## Abstract

Project Summary/Abstract
 Seasonal H3N2 influenza virus evolves rapidly, readily accumulating mutations in the hemagglutinin
(HA) surface protein. These mutations confer escape from host immunity and necessitate frequent vaccine
updates. Current approaches for selecting a vaccine strain rely on characterizing the antigenic properties of
circulating strains using the hemagglutination inhibition (HAI) assay. This is a low-throughput and labor-
intensive process. Additionally, HAI assays use ferret sera, a surrogate which do not fully reflect the epitope-
targeting of antibodies in human sera. Therefore, better strategies are needed to characterize the effects of
mutations on antigenicity of HA. The proposed work will use high-throughput approaches to comprehensively
profile antigenic selection on all single amino-acid mutants of a recent H3 HA. These high-resolution profiles
will determine the extent by which mutations change antigenicity and thereby confer escape from host
immunity. To establish an approach for immune selection, the first component of this proposal will involve
creating diverse libraries of mutant viruses carrying all single amino-acid mutations of H3 HA, and imposing
selection on the mutant viruses with a panel of human monoclonal antibodies. Accurate deep sequencing and
computational analyses will quantify the frequency of every mutation from immune selection and an unselected
control condition. These methods will enable comprehensive profiling of the effects of mutations on antibody
escape. Next, the approach will be extended to polyclonal immune selection of the mutant virus libraries with
ferret and human sera. In particular, human sera are expected to provide evolutionarily relevant measures of
antigenic selection on hemagglutinin mutations. Finally, computational approaches will be used to forecast the
evolutionary trajectories of circulating influenza strains based on the antigenic properties of these strains. This
will allow an assessment of the accuracy of implementing ferret and human sera mutational antigenic profiles
to characterize the antigenic properties and evolutionary trajectories of circulating strains. Overall, this work will
provide insight into immune selection on mutations to H3 HA, and will facilitate more effective antigenic
characterization that can inform selection of vaccine strains.

## Key facts

- **NIH application ID:** 9931122
- **Project number:** 5F30AI136326-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Juhye Monica Lee
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $49,465
- **Award type:** 5
- **Project period:** 2018-07-01 → 2021-06-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9931122

## Citation

> US National Institutes of Health, RePORTER application 9931122, Comprehensive antigenic mapping of seasonal influenza viruses (5F30AI136326-03). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9931122. Licensed CC0.

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