Bloom lab
@jbloomlab.bsky.social
Lab studying molecular evolution of proteins and viruses. Affiliated with Fred Hutch & HHMI. Opinions are my own and do not reflect those of my employer. https://jbloomlab.org/
In new study led by @bdadonaite.bsky.social, we show many influenza HAs (H5, H7, H9, H1, H2, H3) can use avian or human MHC-II to enter cells. We then use novel combo of deep mutational scanning & cryoEM to define how H5 HA binds to avian MHC-II. Preprint: doi.org/10.64898/202...
Here are the slides I am presenting at this morning's @ceirrnetwork.bsky.social seminar related to characterizing the human neutralizing antibody landscape to human seasonal influenza for purposes such as vaccine strain selection: slides.com/jbloom/flu-s...
flu-seqneut-2025to2026
Near real-time data on the human neutralizing antibody landscape to influenza virus to inform vaccine-strain selection in September 2025
slides.com
In new study led by Brendan Larsen, we map functional constraint across the Nipah virus F protein to define constrained epitopes for antibody targeting and identify mutations that stabilize the prefusion conformation for vaccine immunogens. www.pnas.org/doi/10.1073/...
Functional and antigenic constraints on the Nipah virus fusion protein | PNAS
Nipah virus is a highly pathogenic virus in the family Paramyxoviridae that utilizes two distinct surface glycoproteins to infect cells. The recept...
pnas.org
In new study we examine constraints on evolution of endemic "common-cold" coronavirus 229E We find strong tradeoff between antibody neutralization & receptor binding, due to up-down position of spike RBD www.biorxiv.org/content/10.6... See lead author Sheri Harari's summary: x.com/SheriHarari/...
biorxiv.org
Our preprint examining the specificity of human antibodies that cross-react with subclade K H3N2 viruses was posted this morning on medRxiv. These studies have implications on what vaccine strains should be selected for next year’s influenza season. 1/ www.medrxiv.org/content/10.6...
Mapping the specificity of H3N2 strain-specific and cross-reactive human neutralizing antibodies elicited by the 2025-2026 influenza vaccine
An H3N2 variant, named subclade K, continues to circulate widely during the 2025-2026 influenza season. This virus possesses a hemagglutinin (HA) protein that has eleven substitutions relative to the ...
medrxiv.org
We have posted data providing real-time measurement of human neutralizing antibody landscape to seasonal influenza. Data explain spread of subclades K (H3N2) & D.3.1.1 (H1N1), identify subclade K subvariants w reduced neutralization, & can inform choice of strains for next vaccine.
In new work by @jahn0.bsky.social and I in @jbloomlab.bsky.social, we investigate how sequence constraints differ across influenza HA subtypes. We find ~50% of sites in HA display substantially different amino-acid preferences across H3, H5, and H7. doi.org/10.64898/202...
Influenza hemagglutinin subtypes have different sequence constraints despite sharing extremely similar structures
Hemagglutinins (HA) from different influenza A virus subtypes share as little as ∼40% amino acid identity, yet their protein structure and cell entry function are highly conserved. Here we examine the extent that sequence constraints on HA differ across three subtypes. To do this, we first use pseudovirus deep mutational scanning to measure how all amino-acid mutations to an H7 HA affect its cell entry function. We then compare these new measurements to previously described measurements of how all mutations to H3 and H5 HAs affect cell entry function. We find that ∼50% of HA sites display substantially diverged preferences for different amino acids across the HA subtypes. The sites with the most divergent amino-acid preferences tend to be buried and have biochemically distinct wildtype amino acids in the different HA subtypes. We provide an example of how rewiring the interactions among contacting residues has dramatically shifted which amino acids are tolerated at specific sites. Overall, our results show how proteins with the same structure and function can become subject to very different site-specific evolutionary constraints as their sequences diverge. ### Competing Interest Statement JDB consults for Apriori Bio, Invivyd, Pfizer, GSK, and the Vaccine Company. JDB and BD are inventors on Fred Hutch licensed patents related to the deep mutational scanning of viral proteins. National Institute of Allergy and Infectious Diseases, R01AI165821, 75N93021C00015 U.S. National Science Foundation, DGE-2140004 Howard Hughes Medical Institute, https://ror.org/006w34k90
doi.org
Just out📢 Our new paper published in @natmicrobiol.nature.com describes highly potent cross-neutralizing human monoclonal antibodies against H5Nx influenza viruses. Close collaboration with Sara Andrews lab and Tongqing Zhou lab at the VRC. Link to the article: rdcu.be/eKV9T 1/2
In new study led by @ckikawa.bsky.social, we provide near real-time data on human neutralizing antibody landscape to influenza by measuring ~26,000 titers to >100 recent viral strains Data can inform vaccine selection & evolutionary/epidemiological modeling www.biorxiv.org/content/10.1...
Near real-time data on the human neutralizing antibody landscape to influenza virus to inform vaccine-strain selection in September 2025
The hemagglutinin of human influenza virus evolves rapidly to erode neutralizing antibody immunity. Twice per year, new vaccine strains are selected with the goal of providing maximum protection again...
biorxiv.org
In new study led by Xiaohui Ju, we define how mutations to Chikungunya virus envelope proteins affect entry in human vs mosquito cells. Sheds light on functional constraints & enables us to make loss-of-tropism mutants, which could be of use for vaccines. www.biorxiv.org/content/10.1...
Determinants of human versus mosquito cell entry by the Chikungunya virus envelope proteins
Chikungunya virus (CHIKV) infects both humans and mosquitoes during its transmission cycle. How the virus’s envelope proteins mediate entry in cells from such different species is unclear. MXRA8 is a ...
biorxiv.org
In new study led by @bdadonaite.bsky.social, we measure how spike mutations affect function & antigenicity of spike of KP.3.1.1 strain of SARS-CoV-2. Sheds light on how key neutralizing epitopes are changing & importance of RBD up/down motion. www.biorxiv.org/content/10.1...
Spike mutations that affect the function and antigenicity of recent KP.3.1.1-like SARS-CoV-2 variants
SARS-CoV-2 is under strong evolutionary selection to acquire mutations in its spike protein that reduce neutralization by human polyclonal antibodies. Here we use pseudovirus-based deep mutational sca...
biorxiv.org
Our lab has an opening for a research technician to contribute to our efforts to understand RSV evolution & its impact on antibody countermeasures (see journals.asm.org/doi/full/10....). The tech will also help w lab management. If interested, apply here: careers-fhcrc.icims.com/jobs/29940/job
Wanted to flag this interesting study led by our collaborators @kinglabipd.bsky.social suggesting that at least in some contexts, the immunogenicity of H5 influenza vaccines can be improved by mutations that stabilize the HA protein.
King Lab@kinglabipd.bsky.social · last yr.🚨 New paper alert! 🚨 Here we show that stabilized influenza hemagglutinin HPAI H5 immunogens improve the quality of elicited antibody responses. Thank you to @open_phil for funding this work! bit.ly/4lgr0rM
In new study led by @timyu.bsky.social, we measure how mutations to H3 flu HA affect cell entry, stability & antibody escape We find pleiotropic effects of mutations on these phenotypes shape evolution: epistasis alleviates cell-entry but not stability constraints www.biorxiv.org/content/10.1...
Pleiotropic mutational effects on function and stability constrain the antigenic evolution of influenza hemagglutinin
The evolution of human influenza virus hemagglutinin (HA) involves simultaneous selection to acquire antigenic mutations that escape population immunity while preserving protein function and stability...
biorxiv.org
In study led by @ckikawa.bsky.social & Andrea Loes, we use new assay to measure ~10,000 neutralization titers to recent influenza strains & show titers correlate w evolutionary success of viral strains Similar data could help forecast evolution for vaccine selection www.biorxiv.org/content/10.1...
High-throughput neutralization measurements correlate strongly with evolutionary success of human influenza strains
Human influenza viruses rapidly acquire mutations in their hemagglutinin (HA) protein that erode neutralization by antibodies from prior exposures. Here, we use a sequencing-based assay to measure neu...
biorxiv.org
In study led by @csimonich.bsky.social & Teagan McMahon, we quantify antigenic evolution of RSV F Important because: 1️⃣ RSV top cause of infant hospitalization in USA 2️⃣ New antibodies & vax can prevent hospitalizations 3️⃣ Will virus evolution erode their efficacy? www.biorxiv.org/content/10.1...
RSV F evolution escapes some monoclonal antibodies but does not strongly erode neutralization by human polyclonal sera
Vaccines and monoclonal antibodies targeting the respiratory syncytial virus (RSV) fusion protein (F) have recently begun to be widely used to protect infants and high-risk adults. Some other viral pr...
biorxiv.org
In a new study led by Caelan Radford, we use deep mutational scanning to systematically compare the escape mutations from two broadly neutralizing antibodies in a clade A versus clade B HIV Envelope. www.biorxiv.org/content/10.1...
Comprehensive maps of escape mutations from antibodies 10-1074 and 3BNC117 for Envs from two divergent HIV strains
Antibodies capable of neutralizing many strains of HIV are being explored as prophylactic and therapeutic agents, but viral escape mutations pose a major challenge. Efforts have been made to experimen...
biorxiv.org
In new study, we find dramatic differences in specificities of serum neutralizing antibodies in infants w single infection by a recent SARS-CoV-2 strain versus adults/children imprinted by an early viral strain. www.biorxiv.org/content/10.1...
SARS-CoV-2 neutralizing antibody specificities differ dramatically between recently infected infants and immune-imprinted individuals
The immune response to viral infection is shaped by past exposures to related virus strains, a phenomenon known as imprinting. For SARS-CoV-2, much of the population has been imprinted by a viral spik...
biorxiv.org
In new study, we measure how all mutations to rabies G affect cell entry & antibody neutralization Sheds light on constraints on type III fusion proteins, suggests ways to stabilize G vaccine antigens, and quantifies antibody robustness to rabies variation www.biorxiv.org/content/10.1...
Deep mutational scanning of rabies glycoprotein defines mutational constraint and antibody-escape mutations
Rabies virus causes nearly 60,000 human deaths annually. Antibodies that target the rabies glycoprotein (G) are being developed as post-exposure prophylactics, but mutations in G can render such antib...
biorxiv.org
I’ve updated SARSCoV2 RBD antibody-escape calculator w new deep mutational scanning data of Yunlong Cao & Fanchong Jian. My interpretation: antigenic evolution currently constrained by pleiotropic effects of mutations on RBD-ACE2 affinity, RBD up-down position & antibody neutralization
Hi friends new and old! I study how microbes interact and evolve in complex communities like the human gut microbiome.🦠🧬💩 I'm thrilled to share that I'm starting a lab at UC Irvine in April 2025 and am recruiting at all levels - please spread the word! kxuelab.com More about my work below...🧵1/n
Xue lab at UC Irvine
Ecology and evolution in the human gut microbiome
kxuelab.com
If you are searching literature, these sites are E190 and Q226 in H3 numbering, E186 and Q222 in mature H5 numbering, and E202 and Q238 in sequential H5 numbering (see: dms-vep.org/Flu_H5_Ameri...)
HA sequencing numbering | Deep mutational scanning of H5 influenza HA
Interactive figures and detailed results for deep mutational scanning of the HA from the clade 2.3.4.4b A/American Wigeon/South Carolina/USDA-000345-001/2021 (H5N1) strain.
dms-vep.org
Excellent summary thread here by @scottehensley.bsky.social. To add a few more important notes, the sequence (GISAID EPI_ISL_19548836) is ambiguous at *both* site Q226 (as Scott mentions above) and site E190 (H3 numbering) Both these sites play an important role in sialic acid binding specificity
The preliminary sequence from the H5N1 human case in British Columbia has been posted and it is not good news. The virus potentially has a quasispecies at HA residue 226 (H3 numbering). This is bad news because we know that mutations at residue 226 can increase binding to human receptors. 1/
The final version of our study using pseudovirus deep mutational scanning to measure the effects of mutations influenza H5 hemagglutinin to inform viral surveillance is now published in PLoS Biology: journals.plos.org/plosbiology/...
Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance
H5 influenza is considered a potential pandemic threat. Using deep mutational scanning, this work reveals how the >10,000 different possible amino-acid mutations in hemagglutinin affect cell entry, re...
journals.plos.org
Below is brief analysis of HA mutations in two recent cases of H5N1 influenza in humans w contact w dairy cattle in California. Summary is that while virus continues to evolve, nothing about HA mutations in these human cases is obviously alarming.
Our paper describing a new sequencing-based neutralization assay for influenza virus is now published in Journal of Virology: journals.asm.org/doi/10.1128/... This new approach makes it possible to measure 100s (or even ~1000) neutralization titers in a single 96-well plate.
Here is analysis of HA mutations in H5 influenza case in Missouri resident without known contact w animals or raw milk. TLDR: there is one HA mutation that strongly affects antigenicity, and another that merits some further study.
We’ve updated our pre-print on deep mutational scanning of influenza clade 2.3.4.4b H5 HA to identify recent viruses w mutations that alter relevant phenotypes. This identifies viruses w >10x reduced neutralization by sera from candidate vaccine viruses: www.biorxiv.org/content/10.1...
