Near-real time mapping of the human neutralizing antibody landscape to influenza to inform vaccine selection

 

Jesse Bloom

Fred Hutch Cancer Center / HHMI

 

 

 

1) Sequencing-based neutralization assays to rapidly measure how human serum antibodies neutralize many viral strains.

 

2) Near real-time data on the current human neutralizing antibody landscape.

Sequencing-based neutralization assays

Traditional neutralization assays are low throughput (each row measures one serum vs one virus)

fraction infectivity

Sequencing-based neutralization assays measure titers to many strains at once

Loes et al (2024); Kikawa et al (2026)

Loes et al (2024); Kikawa et al (2026)

Sequencing-based neutralization assays measure titers to many strains at once

Loes et al (2024); Kikawa et al (2026)

Sequencing-based neutralization assays measure titers to many strains at once

different recent H3N2 viral strains

Measure titers to many strains for each serum

child has low titers to these strains

Kikawa et al (2026)

Kikawa et al (2026)

different recent H3N2 viral strains

Strain-specific titers differ among people

child has low titers to these strains

adult has low titers to these strains

Near real-time data on the current human neutralizing antibody landscape

Near real-time measurement of titers to recent strains to inform vaccine choice

All data openly shared as it is collected, so anyone can analyze it to inform vaccine-strain selection and advance public health.

 

Currently generating data for A/H3N2 and A/H1N1; hope to expand to influenza B.

 

Data shared so far:

I will discuss latest data, much of which was generated in last month

In May, we chose set of recent seasonal strains

Most recently sequenced human influenza within one HA1 mutation of strain in our set

Most recently sequenced human influenza within one HA1 mutation of strain in our set

Measured neutralization of 78 H3N2 and 62 H1N1 strains by 325 human sera

Human sera collected between April and June of 2026:

  • 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

 

H3N2 results

Low titers to some emerging subclade K variants

Lowest titers are to subclade K variants with mutation at sites 222 or 223.

 

See also:

Sites 222 and 223 are in region of HA not mutated in original subclade K

Mutations at these sites likely erode residual antibodies not already escaped by earlier subclade K mutations; see Liu et al (2026).

V223I is recurrently spreading in subclade K

H1N1 results

Low titers to D.3.1.1, especially with G155E

Most D.3.1.1 strains have lower titers than current D.3.1 vaccine.

 

Titers lowest to strains with G155E.

 

See also:

G155E most affects potent sera from 15-25 yr olds

D.3.1.1 has several mutations relative to D.3.1, with G155E an additional change

D.3.1.1 now dominates, G155E spreading

Conclusions

 

Sequencing-based neutralization assays can measure the neutralization of recent strains by current human antibodies in near real time.

 

We are generating and sharing large datasets twice per year.

 

Current data suggests:

  • H3N2 subclade K variants with mutations in antigenic region D (eg, V223I)
  • H1N1 subclade D.3.1.1 has advanced over D.3.1, watch G155E variant

Thanks

All data: https://github.com/jbloomlab/flu-seqneut-2026

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

EPI-HK: Ben Cowling, Nancy Leung, Faith Ho

NIID Japan: Shinji Watanabe, Hideki Hasegawa

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