A collection of thoughts, ideas, and projects from the Bloom Lab team.
In a new study led by Catherine Jacob-Dolan, we show SARS-CoV-2's spike RBD has evolved reduced inherent antigenicity as quantified by decreased recognition by naive human B cells.
Today we posted a preprint describing work led by Caroline Kikawa and Andrew Butler using sequencing-based neutralization assays to characterize the human neutralizing antibody landscape to influenza virus. Our results underscore the impact of the H1N1 HA mutation G155E on a subset of the human population.
Our study led by Cassie Simonich that characterizes how mutations to RSV F affect monoclonal antibodies was just published in Nature. This paper uses pseudovirus deep mutational scanning to measure how all F mutations affect clinical antibodies nirsevimab and clesrovimab, and provides a biophysical model that explains why escape from nirsevimab is more commonly observed in subtype B than A.
We just posted to bioRxiv a new study led by Bernadeta Dadonaite that uses a novel combination of deep mutational scanning and cryo-EM to show how influenza HA interacts with MHC-II. Many important questions remain about how this interaction evolves and its biological role, and determining its structural basis is a first step towards answering those questions.
We just posted to bioRxiv a new study that measures the current human neutralizing antibody landscape to human seasonal influenza. These data help explain the recent spread of new subclades of H3N2 and H1N1 influenza, and can help inform the upcoming decision on which strains to choose for the 2026-2027 Northern Hemisphere influenza vaccine.
In a new study led by Caroline Kikawa and recently posted on bioRxiv, we use a new high-throughput method to measure ~26,000 neutralizing antibody titers that help capture the current human neutralizing antibody landscape to influenza. We think these data can enable better evolutionary / epidemiological forecasting for purposes like influenza vaccine strain selection.
In a new study led by Xiaohui Ju and recently posted on bioRxiv, we measure how mutations the Chikungunya virus envelope proteins affect entry in human vs mosquito cells. The results help elucidate how this virus can infect cells from such diverse species, and enable us to create loss-of-tropism mutants that can only efficiently infect cells from one species.
In a new study led by Bernadeta Dadaonaite and posted on bioRxiv today, we used pseudovirus deep mutational scanning to understand how mutations affect the function and antigenicity of a recent SARS-CoV-2 variant that is fairly similar to those circulating right now.
In a new study led by grad student Tim Yu and posted on bioRxiv today, we used pseudovirus deep mutational scanning to measure how all mutations to a recent H3N2 HA affect cell entry, stability, and antibody escape. The results help shed light on how the pleiotropic effects of mutations shape influenza evolution.
In a new study posted on bioRxiv today, we used high-throughput sequencing-based neutralization assays to measure ~10,000 titers representing the ability of different human sera to neutralize different H3N2 influenza strains. We then showed that these titers correlate with the actual evolutionary success of these viral strains in the real world, suggesting such experiments could be useful for helping inform vaccine-strain selection.
In a new study posted on bioRxiv today, we developed a pseudovirus neutralization assay for RSV's F protein, and then used that assay to quantify the extent of antigenic evolution of F. We think this is an important study because RSV is a top cause of infant hospitalizations, and antibodies and vaccines are coming into widespread use.
In a new study that we posted on bioRxiv today, we showed that there are striking differences in how serum neutralizing antibodies target the SARS-CoV-2 spike depending on a person's exposure history. This result suggests that growing population immune heterogeneity is likely becoming of growing importance in shaping SARS-CoV-2 evolution.
In a new study we posted on bioRxiv today, we measured how all mutations to the rabies virus glycoprotein (G) affect cell entry and antibody neutralization. This study sheds light on mutational constraints on class III viral fusion proteins, suggests ways to stabilize G for vaccine antigens, and quantifies the robustness of antibodies (including ones being used or developed for clinical use) to rabies genetic variation.
I've updated the SARS-CoV-2 RBD antibody escape calculator with new yeast-display deep mutational scanning data from Yunlong Cao's group. My interpretation: the antigenic evolution of the RBD is currently constrained by the pleiotropic effects of mutations on 1:1 RBD-ACE2 affinity, up-down RBD positioning in the context of full spike, and antibody neutralization.
In a paper just published in Journal of Virology, we describe a new sequencing-based neutralization assay that dramatically increases the scale at which it is possible to measure how sera or antibodies neutralize different influenza virus strains.
In a new study, we have measured how all mutations to the hemagglutinin (HA) of clade 2.3.4.4b H5 influenza affect molecular phenotypes relevant to pandemic risk. The data can be interactively visualized at https://dms-vep.org/Flu_H5_American-Wigeon_South-Carolina_2021-H5N1_DMS/