Mapping the human neutralizing antibody landscape to inform influenza vaccine selection

 

Jesse Bloom

Fred Hutch Cancer Center / HHMI

October 28, 2026

 

These slides: https://slides.com/jbloom/biohub2026

For details on this year's early influenza season, see Nature News, Celine Gounder, or The Seattle Times

Human seasonal influenza evolves rapidly

Year

HA amino-acid mutations

HA of human H3N2 influenza has accumulated ~50 mutations over last two decades. x indicates vaccine strains.

0

2010

10

20

30

40

50

2014

2018

2022

2026

HA evolution fixes mutations at surface sites targeted by neutralizing antibodies

Vaccines updated regularly due to viral evolution, currently involves ~9 month lag

In February strains chosen for Northern Hemisphere vaccine administered ~October that year.

In September, strains chosen for Southern Hemisphere vaccine administered the next ~May.

Separate update decisions for H3N2, H1N1, and B strains; not every component changed each time.

Antibody titers to different strains can be measured by neutralization assay

fraction infectivity

But traditional neutralization assays are low throughput

fraction infectivity

We developed sequencing-based neutralization to measure titers to many strains at once

We developed sequencing-based neutralization to measure titers to many strains at once

We developed sequencing-based neutralization to measure titers to many strains at once

different recent viral strains

We measure each person's antibody titers to many viral strains

child has low titers to these strains

different recent viral strains

Titers to different strains differ among people

child has low titers to these strains

adult has low titers to these strains

Current human neutralizing antibody landscape to influenza

We chose set of recent human seasonal strains

Most recent sequenced human influenza strains similar to a strain in our set

Measured neutralization of these strains by 355 recently collected human sera 

  • Seattle Children's Hospital: convenience samples
  • University of Washington Medical Center: convenience samples
  • Creative Testing Solutions / UCSF: samples from blood donors
  • Victorian Infectious Diseases Lab (Australia): pre- or post-vaccine samples

 

Low titers to strains with G155E

G155E causes largest reduction in neutralization for sera from younger individuals

G155E strains are spreading

Conclusions

 

We can measure human neutralizing antibody landscape in near real-time at scale.

 

Data explain why H1N1 strains with G155E are causing early cases, especially in younger individuals.

 

These data can help inform vaccine update decisions.

Thanks

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

University of Washington: Alex Greninger

Penn: Scott Hensley, Jiaojiao Liu, Sydney Gang, Elizabeth Drapeau, Tachianna Griffiths

Cambridge: Sam Turner, Derek Smith

Basel: Richard Neher

NIID Japan: Shinji Watanabe, Hideki Hasegawa

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