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Influenza NA Cross-Reactive Antibodies

1:31:47 recording · AUTO · 4 speakers

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Brief overview

Two papers: a sialic-acid-mimicking antibody crosses flu neuraminidases, and gut-derived brain T cells shape feeding behaviour.

  1. Antibodies can mimic sialic acid to block neuraminidaseHB420's CDR H3 sits in the active site the way sialic acid would, and antibodies to HA do the same trick.
  2. Germline binds N2, hypermutation adds N1 cross-reactivityReverting all the somatic hypermutations left N2 binding intact but lost H5N1 binding, and heavy-chain changes did most of the work.
  3. Gut T cells reach the brain and change behaviourInterferon gamma-producing CD4 T cells enriched in the subfornical organ were required for normal latency to eat in the novelty suppressed feeding test.
Executive Summary AI
  • Vincent presents a Cell Host & Microbe snippet on the evolution of antibody cross-reactivity to H5N1 neuraminidase from an N2-specific germline, first author Huibin Luv, corresponding authors Chris Mock and Nicholas Wu of the University of Illinois and the Chinese University of Hong Kong.5:43
  • The group screened plasma from 245 healthy people in Hong Kong collected between January and March 2020 and found anti-neuraminidase antibodies against H1N1, H3N2 and even H5N1, higher in younger age groups, which they attribute to imprinting by H1N1 infection.9:11
  • A phage display library yielded a single public clone, HB420, and its structure with an H3N2 neuraminidase shows the CDR H3 inserting into the enzyme's active site and mimicking sialic acid, while an N-linked glycosylation site acquired at residue 245 since 2016 blocks binding to recent human H3N2 strains.17:18
  • In mice, HB420 gave complete protection against H3N2 with 100% survival and minimal weight loss, 40% survival and a two-log lung titre reduction against a virus bearing the N1 of H5N1, and a LALA variant lost that protection, pointing to Fc effector functions rather than neutralisation.29:03
  • Steph then covers a Nature paper from May 2025 by Tamami Yoshida and Andrew Wang at Yale showing that the subfornical organ holds gut-derived CD4 T cells in mice and in human autopsy tissue, and that interferon gamma from those cells, along with CXCR6, is needed for normal feeding behaviour in a stress test.33:30
Key Quote
“So the interesting part of this paper is they solve the structure of this antibody, HB420, to an H3N2NA, right?”
— Vincent Racaniello17:18
Key Quote
“So they're painting this picture that in the gut, these T-cells can migrate to the brain.”
— Steph Lange1:03:55
Key Quote
“So are you convinced that there are a specific subset of FTC cells in the parenchyma?”
— Vincent Racaniello1:25:40