Jesse Bloom PRO
Scientist studying evolution of proteins and viruses.
Near-real time mapping of the human neutralizing antibody landscape to inform vaccine selection
Jesse Bloom
Fred Hutch Cancer Center / HHMI
CEPI Workshop
October 15, 2026
These slides: https://slides.com/jbloom/cepi2026
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
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 informative about real-world 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.
Data shared so far:
In May, we chose set of recent seasonal strains
Most recently sequenced human influenza within one HA1 mutation of strain in our set
Measured neutralization of 148 strains by 355 human sera (52,268 titers)
Human sera assayed (all 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
Low H1N1 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 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 influenza datasets twice per year.
Current data suggests H1N1 subclade D.3.1.1 strains with G155E have major antigenic change, especially in younger individuals
We hope to generalize this approach to other viruses!
Thanks
These slides: https://slides.com/jbloom/cepi2026
Most recent data: https://jbloomlab.github.io/flu-seqneut-2026/summary.html
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
cepi2026
By Jesse Bloom
cepi2026
Near-real time mapping of the human neutralizing antibody landscape to influenza to inform vaccine selection
