High-throughput characterization of the human neutralizing antibody landscape to seasonal influenza

Jesse Bloom

Fred Hutch Cancer Center / HHMI

These slides at https://slides.com/jbloom/flu-seqneut-2025to2026

Measure neutralization titers of recent human sera against current human seasonal H3N2 and H1N1 influenza strains.

Share data to inform strain selection for next vaccine.

Overall, we measured titers of 302 human sera against 91 viral strains for 27,409 neutralization titers.

Challenge 1:

Human seasonal influenza is variable

Strains we chose cover circulating human seasonal influenza as of early 2026

Chose 57 H3N2 strains

Chose 34 H1N1 strains

Most recently sequenced human strains within one HA1 mutation of chosen strains

Challenge 2:

Human influenza immunity is variable

Influenza infects people of different ages, who have different immunity due to different exposure histories.

Influenza transmits around the world, spreading within and between countries.

To forecast which virus an elderly person in the United States might be exposed to next year, we need to understand immunity across ages and geographies.

Influenza evolves in global population

We assembled 302 sera from humans of different ages and locations

Challenge 3:

How do we rapidly measure neutralization of 91 viruses by 302 human sera?

Sequencing-based neutralization assays simultaneously measure titers to many strains

Loes et al (2024); Kikawa et al (2025)

Sequencing-based neutralization assays simultaneously measure titers to many strains

Loes et al (2024); Kikawa et al (2025)

Sequencing-based neutralization assays simultaneously measure titers to many strains

Loes et al (2024); Kikawa et al (2025)

Real-time measurement of human neutralizing antibody landscape to influenza

For H3N2, lowest titers to subclade K, which has recently become dominant

For H1N1, lowest titers to subclade D.3.1.1, which has recently become dominant

Age-specific patterns: subset below plot to ages 10 to 25

What strains might spread next?

Lowest titers are to subclade K strains with additional mutations in antigenic regions D or E

See Liu et al (2026) for more details.

Subclade K has many mutations, but not in antigenic regions D and E. So new variants with additional mutations in those regions may spread in future.

For more information...

• These slides: https://slides.com/jbloom/flu-seqneut-2025to2026
• Papers describing this work
  • Kikawa et al (2026)
  • Liu et al (2026) [related paper from Hensley lab]
• Interactive phylogenetic trees with titer data
  • H3N2
  • H1N1
• Data and computer code: https://github.com/jbloomlab/flu-seqneut-2025to2026
• Additional visualizations: https://jbloomlab.github.io/flu-seqneut-2025to2026

These slides: https://slides.com/jbloom/flu-seqneut-2025to2026

Thanks

Fred Hutch

Caroline Kikawa

John Huddleston

Andrea Loes

Penn

Jiaojiao Liu

Sydney Gang

Scott Hensley

Fred Hutch / Seattle Childrens: Trevor Bedford, Janet Englund, Kirsten Lacombe

Penn: Elizabeth Drapeau, Tachianna Griffiths

Cambridge: Sam Turner, Derek Smith

Basel: Richard Neher

Hong Kong: Ben Cowling, Nancy Leung, Faith Ho

NIID Japan: Shinji Watanabe, Hideki Hasegawa

UCSF / Red Cross: Michael Busch, Marion Lanteri, Mars Stone, Bryan Spencer