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

Assays measure just one virus against one serum in each row (or column) of a 96-well plate

Loes et al (2024)

Loes et al (2024)

Loes et al (2024)

Loes et al (2024)

Full viral library assayed in each row of plate

Loes et al (2024)

Full viral library assayed in each row of plate

Loes et al (2024)

Full viral library assayed in each row of plate

Loes et al (2024)

Neutralization of all the different viruses is read out simultaneously be sequencing

Loes et al (2024)

Neutralization of all the different viruses is read out simultaneously be sequencing

Loes et al (2024)

Neutralization of all the different viruses is read out simultaneously be sequencing

Loes et al (2024)

Neutralization of all the different viruses is read out simultaneously be sequencing

Loes et al (2024)

Neutralization of all the different viruses is read out simultaneously be sequencing

Loes et al (2024)

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

Kikawa et al, eLife (2025)

Person-to-person variation in per-strain titers

Kikawa et al, eLife (2025)

Heterogeneity within and between age groups

Kikawa et al, eLife (2025)

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

Kikawa et al, eLife (2025)

sera from 95 individuals of different ages

Measured neutralization by pool of all sera

We measured neutralization for a large set of sera in two ways

Kikawa et al, eLife (2025)

Kikawa et al, eLife (2025)

We calculated actual growth rates of different strains in human population

But viral growth rates do not correlate with titers of a pool of all serum

Kikawa et al (2025)

Can we measure human neutralizing antibody landscape in near real-time?

Kikawa et al, bioRxiv (2025)

Timeline relative to Southern Hemisphere influenza vaccine strain selection

H3N2 strains in library vs global diversity

Kikawa et al, bioRxiv (2025)

Strains in library mostly cover current diversity of human seasonal influenza

Kikawa et al, bioRxiv (2025)

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...

Data: https://github.com/jbloomlab/flu-seqneut-2025 

These slides: https://slides.com/jbloom/ceirr-sab-2025

Thanks