Near real-time tracking of the human neutralizing antibody landscape to influenza virus
Jesse Bloom
Fred Hutch Cancer Center / HHMI
These slides at https://slides.com/jbloom/ceirr-sab-2025
Traditional neutralization assays are low-throughput
Assays measure just one virus against one serum in each row (or column) of a 96-well plate
We developed new assay to measure 1000s of neutralization curves in a single plate
Our sequencing-based neutralization assay uses barcoded virions
Our sequencing-based neutralization assay uses barcoded virions
Full viral library assayed in each row of plate
Full viral library assayed in each row of plate
Full viral library assayed in each row of plate
Neutralization of all the different viruses is read out simultaneously be sequencing
Neutralization of all the different viruses is read out simultaneously be sequencing
Neutralization of all the different viruses is read out simultaneously be sequencing
Neutralization of all the different viruses is read out simultaneously be sequencing
Neutralization of all the different viruses is read out simultaneously be sequencing
Neutralization of all the different viruses is read out simultaneously be sequencing
different recent H3N2 viral strains
Each row of plate measures titers to many viruses. Below are titers for one child serum.
this child has low titers to these viral strains
Person-to-person variation in per-strain titers
Heterogeneity within and between age groups
How do these heterogeneous neutralization titers for different humans shape viral evolution?
We measured neutralization for a large set of sera in two ways
sera from 95 individuals of different ages
Measured neutralization by each individual serum
sera from 95 individuals of different ages
Measured neutralization by each individual serum
Measured neutralization by pool of all sera
We measured neutralization for a large set of sera in two ways
We calculated actual growth rates of different strains in human population
Growth rates of influenza strains correlate with fraction of sera with titer below cutoff
But viral growth rates do not correlate with titers of a pool of all serum
Can we measure human neutralizing antibody landscape in near real-time?
Timeline relative to Southern Hemisphere influenza vaccine strain selection
H3N2 strains in library vs global diversity
Strains in library mostly cover current diversity of human seasonal influenza
We measured neutralization titers of 188 human sera to 140 strains (~26,000 titers total)
We're still analyzing data to figure out how to best use them to inform evolutionary forecasts...
Exciting it is now possible to measure human influenza neutralizing antibody landscape in near real-time.
We're working to do the same for other viruses...
Lots of exciting experiments and analyses to come...
