Jesse Bloom PRO
Scientist studying evolution of proteins and viruses.
Near-real time mapping of the human neutralizing antibody landscape to influenza to inform vaccine selection
Jesse Bloom
Fred Hutch Cancer Center / HHMI
Options for Control of Influenza Meeting
August 30, 2026
These slides: https://slides.com/jbloom/options2026
Year
HA amino-acid mutations
Hemagglutinin (HA) of human influenza evolves rapidly
HA of human H3N2 influenza has accumulated >45 mutations over last 18 years. x indicates vaccine strains.
HA evolution fixes mutations in regions targeted by neutralizing antibodies
Due to influenza evolution, vaccine updated ~9 months before it will be used each year
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.
Antigenically charactering influenza strains in near real-time to inform vaccine choice
1) Sequencing-based neutralization assays to rapidly measure how human serum antibodies neutralize many viral strains.
2) Proof-of-principle: human serology helps explain real-world viral evolution.
3) 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
Sequencing-based neutralization assays measure titers to many strains at once
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
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
Proof-of-principle: human serology helps explain real-world viral evolution
Measured neutralization for large set of sera against many strains
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
Measured neutralization by the same set of sera as a pool
Estimated actual growth rates of different strains in human population
Multinomial logistic regression fits to estimate strain growth
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
A strain's antigenic success depends on fraction of humans with low titers to it
See also Kim, ..., Cobey (2024)
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:
- Aug/Sep 2025: https://github.com/jbloomlab/flu-seqneut-2025; Kikawa et al (2025)
- Jan/Feb 2026: https://github.com/jbloomlab/flu-seqneut-2025to2026; Kikawa et al (2026)
- Aug/Sep 2026: https://github.com/jbloomlab/flu-seqneut-2026; unpublished
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:
- Aug/Sep 2025: https://github.com/jbloomlab/flu-seqneut-2025; Kikawa et al (2025)
- Jan/Feb 2026: https://github.com/jbloomlab/flu-seqneut-2025to2026; Kikawa et al (2026)
- Aug/Sep 2026: https://github.com/jbloomlab/flu-seqneut-2026; unpublished
I will discuss latest data, much of which was generated in last two weeks and is still incompletely analyzed (so examine yourself too!)
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 >200 human sera
Human sera assayed (all collected between April and June of 2026):
- Seattle Children's Hospital: 40 convenience samples
- University of Washington Medical Center: 88 convenience samples
- Creative Testing Solutions / UCSF: 32 samples from blood donors
- Victorian Infectious Diseases Lab (Australia): 58 pre- or post-vaccine samples
[Numbers as of Aug-28-2026, more sera still being assayed]
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.
These titer measurements are informative about influenza evolution.
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
These slides: https://slides.com/jbloom/options2026
Most recent 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
options2026
By Jesse Bloom
options2026
Near-real time mapping of the human neutralizing antibody landscape to influenza to inform vaccine selection
