From 3a9400aeae89a0b935610728a9213e11a1ba27a4 Mon Sep 17 00:00:00 2001 From: jbloom Date: Wed, 16 Sep 2026 09:32:40 -0700 Subject: [PATCH 1/2] update 2026_simonich to _Nature_ version --- papers/2026_simonich_dms.md | 13 +++++++------ 1 file changed, 7 insertions(+), 6 deletions(-) diff --git a/papers/2026_simonich_dms.md b/papers/2026_simonich_dms.md index e79c6e8d..9e57e914 100644 --- a/papers/2026_simonich_dms.md +++ b/papers/2026_simonich_dms.md @@ -1,16 +1,17 @@ --- layout: paper -title: "Complete definition of how mutations affect antibodies used to prevent RSV" -date: "2026-02-12" +title: "Mutational constraints on RSV F and its neutralization by antibodies" +date: "2026-09-16" authors: - "Cassandra AL Simonich" - "Teagan E McMahon" + - "Gavin Juviler" - "Lucas Kampman" - "Helen Y Chu" - "Jesse D Bloom" -journal: "bioRxiv" -doi: "10.64898/2026.02.12.705519" -link: "https://doi.org/10.64898/2026.02.12.705519" +journal: "Nature" +doi: "10.1038/s41586-026-11030-4" +link: "https://www.nature.com/articles/s41586-026-11030-4" image: "/assets/papers/2026_simonich_dms.png" keywords: - "RSV" @@ -21,7 +22,7 @@ selected: true ## Abstract -New antibodies targeting the F protein of respiratory syncytial virus (RSV) have substantially reduced infant hospitalizations. However, viral resistance is a concern: one antibody failed clinical trials due to emergence of a resistant strain, and sporadic resistance mutations to the most widely used antibody (nirsevimab) have been identified in breakthrough infections. Here we define how RSV F mutations affect antibody neutralization. We first provide a biophysical model of how the buffering effect of bivalent IgG binding combines with differences in monovalent Fab potency to explain why nirsevimab resistance mutations are more common in subtype B than subtype A RSV strains. We then perform pseudovirus deep mutational scanning to safely measure how nearly all mutations to F affect its cell entry function and neutralization by the IgG and Fab forms of nirsevimab, clesrovimab, and several other key antibodies. We use these measurements to enable real-time surveillance of RSV sequences for antibody resistance, and identify rare strains with sporadic resistance mutations. Overall, our work improves understanding of the mechanisms by which viral mutations impact antibody neutralization, enables monitoring for natural RSV strains resistant to antibodies of public-health importance, and can help guide development of future antibodies with resilience to viral escape. +New antibodies targeting the F protein of respiratory syncytial virus (RSV) have substantially reduced infant hospitalizations. However, viral resistance is a concern: one antibody failed clinical trials because of a resistant strain, and sporadic resistance mutations to the most widely used antibody (nirsevimab) have been identified. Here we define how RSV F mutations affect antibody neutralization. We first provide a biophysical model of how the buffering of bivalent IgG binding combines with the lower Fab potency of nirsevimab to subtype B to make resistance to this antibody more common in subtype B than A strains. We then perform pseudovirus deep mutational scanning to safely measure how nearly all mutations to F affect its cell entry function and neutralization by IgG and Fab forms of nirsevimab, clesrovimab and several other key antibodies. We use these measurements to enable real-time surveillance of RSV sequences for antibody resistance, and show that resistant strains have arisen sporadically but are at present rare. Overall, our work shows how Fab potency and epitope specificity combine to determine how viral mutations affect antibody neutralization, enables monitoring for natural RSV strains resistant to antibodies of public-health importance, and can help guide development of future antibodies with resilience to viral escape. ## Interactive visualizations The results described in this paper can be interactively visualized at [https://dms-vep.org/RSV_Long_F_DMS/](https://dms-vep.org/RSV_Long_F_DMS/); all computer code and data is at [https://github.com/dms-vep/RSV_Long_F_DMS](https://github.com/dms-vep/RSV_Long_F_DMS). From 6d0a9154d4408ac8b9b7ef4d2cefb526ccfddf3b Mon Sep 17 00:00:00 2001 From: jbloom Date: Wed, 16 Sep 2026 09:34:32 -0700 Subject: [PATCH 2/2] update 2026_kikawa citation to published paper --- papers/2026_kikawa.md | 8 ++++---- 1 file changed, 4 insertions(+), 4 deletions(-) diff --git a/papers/2026_kikawa.md b/papers/2026_kikawa.md index 64b47415..43988e7d 100644 --- a/papers/2026_kikawa.md +++ b/papers/2026_kikawa.md @@ -1,7 +1,7 @@ --- layout: paper title: "Near real-time data on the human neutralizing antibody landscape to influenza virus as of early 2026 to inform vaccine-strain selection" -date: "2026-02-19" +date: "2026-07-26" authors: - "Caroline Kikawa" - "John Huddleston" @@ -27,9 +27,9 @@ authors: - "Trevor Bedford" - "Scott E Hensley" - "Jesse D Bloom" -journal: "bioRxiv" -doi: "10.64898/2026.02.18.706711" -link: "https://doi.org/10.64898/2026.02.18.706711" +journal: "Virus Evolution" +doi: "10.1093/ve/veag046" +link: "https://doi.org/10.1093/ve/veag046" image: "/assets/papers/2026_kikawa.jpg" selected: false keywords: