diff --git a/papers/2025_yu.md b/papers/2025_yu.md index b77d675..cf86206 100644 --- a/papers/2025_yu.md +++ b/papers/2025_yu.md @@ -23,3 +23,6 @@ selected: false ## Abstract The evolution of human influenza virus haemagglutinin (HA) involves simultaneous selection to acquire antigenic mutations that escape population immunity while preserving protein function and stability. Epistasis shapes this evolution, as an antigenic mutation that is deleterious in one genetic background may become tolerated in another. However, the extent to which epistasis can alleviate pleiotropic conflicts between immune escape and protein function/stability is unclear. Here we measure how all amino acid mutations in the HA of a recent human H3N2 influenza strain affect its cell entry function, acid stability and neutralization by human serum antibodies. We find that epistasis has entrenched certain mutations so that reverting to the ancestral amino acid identity in earlier strains is no longer tolerated. Epistasis has also enabled the emergence of antigenic mutations that were detrimental to the cell entry function of HA in earlier strains. However, epistasis appears insufficient to overcome the pleiotropic costs of antigenic mutations that impair the stability of HA, explaining why some mutations that strongly escape human antibodies never fix in nature. Our results refine our understanding of the mutational constraints that shape recent H3N2 influenza evolution: epistasis can enable antigenic change, but pleiotropic effects can restrict its trajectory. + +## News and Views +See also the [perspective published alongside this article](https://www.nature.com/articles/s41559-025-02928-9). diff --git a/papers/2026_harari.md b/papers/2026_harari.md new file mode 100644 index 0000000..6888c14 --- /dev/null +++ b/papers/2026_harari.md @@ -0,0 +1,29 @@ +--- +layout: paper +title: "Mutations to the HCoV-229E spike have counterbalancing effects on serum antibody neutralization and receptor binding" +date: "2026-02-22" +authors: + - "Sheri Harari" + - "Rachel T Eguia" + - "Bernadeta Dadonaite" + - "Caelan E Radford" + - "Cameron Stewart" + - "David Veesler" + - "Jesse D Bloom" +journal: "bioRxiv" +doi: "10.64898/2026.02.22.707297" +link: "https://doi.org/10.64898/2026.02.22.707297" +image: "/assets/papers/2026_harari.png" +keywords: + - "Coronavirus" + - "Deep mutational scanning" + - "Pseudovirus" +selected: false +--- + +## Abstract + +Human coronavirus 229E (HCoV-229E) is an endemic pathogen that causes repeated "common-cold" infections throughout life. Like other coronaviruses, it accumulates spike mutations that erode antibody immunity and enable reinfection. Here, we use pseudovirus deep mutational scanning to measure how mutations to the HCoV-229E spike affect its cell entry function, binding to its human APN receptor, and neutralization by human sera with a range of sensitivities to erosion by viral evolution. We find that both receptor binding and serum neutralization are affected by mutations across spike, including many that modulate these properties by affecting the balance of up versus down conformations of the spike receptor-binding domain (RBD). In particular, some mutations increase both receptor binding and serum neutralization by shifting the RBD to a more up conformation, suggesting that the HCoV-229E spike has evolved to shield key RBD neutralizing epitopes at the cost of less efficient receptor binding. + +## Interactive visualizations +The results described in this paper can be interactively visualized at [https://dms-vep.org/229E_spike_1984_DMS/](https://dms-vep.org/229E_spike_1984_DMS/); all computer code and data is at [https://github.com/dms-vep/229E_spike_1984_DMS](https://github.com/dms-vep/229E_spike_1984_DMS). diff --git a/papers/2026_loes.md b/papers/2026_loes.md new file mode 100644 index 0000000..48efac8 --- /dev/null +++ b/papers/2026_loes.md @@ -0,0 +1,37 @@ +--- +layout: paper +title: "Strain-specific differences in the response to egg-derived versus recombinant protein influenza vaccines" +date: "2026-02-23" +authors: + - "Andrea N Loes" + - "Rosario AL Tarabi" + - "Shuk H Li" + - "Reilly K Atkinson" + - "John Huddleston" + - "Caroline Kikawa" + - "Tachianna Griffiths" + - "Elizabeth M Drapeau" + - "Sook-San Wong" + - "Samuel MS Cheng" + - "Nancy HL Leung" + - "Sarah Cobey" + - "Benjamin J Cowling" + - "Trevor Bedford" + - "Scott E Hensley" + - "Jesse D Bloom" +journal: "bioRxiv" +doi: "10.64898/2026.02.23.707528" +link: "https://doi.org/10.64898/2026.02.23.707528" +image: "/assets/papers/2026_loes.jpg" +selected: false +keywords: + - "Influenza" + - "Immunity" + - "Sequencing-based neutralization" +--- + +## Abstract +The 2023/2024 influenza vaccine included an updated H1N1 component designed to better match a new clade of H1N1 that had multiple mutations in antigenic epitopes of hemagglutinin. Despite this update, the vaccine trended towards being less effective against the vaccine-matched H1N1 clade than the parental H1N1 clade lacking the new antigenic mutations. Here we measure neutralization titers of serum antibodies from individuals who had received either a recombinant protein or an egg-derived vaccine against a set of viruses with hemagglutinins from 58 H1N1 strains representative of the diversity during the 2023/2024 season. We find that egg-derived vaccine recipients, but not recombinant protein vaccine recipients, had a relatively lower boost in neutralizing titers to the new clade that the updated vaccine was designed to target. We suggest that the difference in the extent that the egg-derived versus recombinant protein vaccines boost neutralizing titers to the new H1N1 clade is because the seed strain for the egg-derived vaccine strain had acquired a reversion of a key antigenic mutation (K142R) present in that clade. Our results show how egg-derived versus recombinant protein vaccines can elicit different relative titer boosts against different subsets of viral strains, a phenomenon that could impact vaccine effectiveness. + +## Data +The neutralization data described in this paper is available at [https://github.com/jbloomlab/flu_seqneut_pdmH1N1_2023-2024_VaccinatedCohorts](https://github.com/jbloomlab/flu_seqneut_pdmH1N1_2023-2024_VaccinatedCohorts). diff --git a/posts/2025-05-27_yu-h3.md b/posts/2025-05-27_yu-h3.md index 9d4ef41..9693a76 100644 --- a/posts/2025-05-27_yu-h3.md +++ b/posts/2025-05-27_yu-h3.md @@ -16,3 +16,6 @@ For accessible summaries of the study, see: - [This X thread](https://x.com/jbloom_lab/status/1927399924519367090) All the data are available for interactive visualization and download at [https://dms-vep.org/Flu_H3_Massachusetts2022_DMS/](https://dms-vep.org/Flu_H3_Massachusetts2022_DMS/) + +## Update +The final version of this article has been [published in _Nature Ecology and Evolution_](https://www.nature.com/articles/s41559-025-02895-1) alongside a [nice News and Views](https://www.nature.com/articles/s41559-025-02928-9). diff --git a/public/assets/papers/2026_harari.png b/public/assets/papers/2026_harari.png new file mode 100644 index 0000000..7ae3048 Binary files /dev/null and b/public/assets/papers/2026_harari.png differ diff --git a/public/assets/papers/2026_loes.jpg b/public/assets/papers/2026_loes.jpg new file mode 100644 index 0000000..7e938a0 Binary files /dev/null and b/public/assets/papers/2026_loes.jpg differ