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TitleNeuraminidase-specific antibodies drive differential cross-protection between contemporary FLUBV lineages.
Journal, issue, pagesSci Adv, Vol. 11, Issue 13, Page eadu3344, Year 2025
Publish dateMar 28, 2025
AuthorsCaroline K Page / Justin D Shepard / Sean D Ray / James A Ferguson / Alesandra J Rodriguez / Julianna Han / Joel C Jacob / Dawne K Rowe-Haas / Jasmine Y Akinpelu / Lilach M Friedman / Tomer Hertz / Andrew B Ward / Stephen M Tompkins /
PubMed AbstractThe two influenza B virus (FLUBV) lineages have continuously diverged from each other since the 1980s, with recent (post-2015) viruses exhibiting accelerated evolutionary rates. Emerging data from ...The two influenza B virus (FLUBV) lineages have continuously diverged from each other since the 1980s, with recent (post-2015) viruses exhibiting accelerated evolutionary rates. Emerging data from human studies and epidemiological models suggest that increased divergence in contemporary viruses may drive differential cross-protection, where infection with Yamagata lineage viruses provides limited immunity against Victoria lineage viruses. Here, we developed animal models to investigate the mechanisms behind asymmetric cross-protection between contemporary FLUBV lineages. Our results show that contemporary Victoria immunity provides robust cross-protection against the Yamagata lineage, whereas Yamagata immunity offers limited protection against the Victoria lineage. This differential cross-protection is driven by Victoria-elicited neuraminidase (NA)-specific antibodies, which show cross-lineage reactivity, unlike those from Yamagata infections. These findings identify a phenomenon in contemporary FLUBV that may help explain the recent disappearance of the Yamagata lineage from circulation, highlighting the crucial role of targeting NA in vaccination strategies to enhance cross-lineage FLUBV protection.
External linksSci Adv / PubMed:40153499 / PubMed Central
MethodsEM (single particle)
Resolution20.0 Å
Structure data

EMDB-47798: Polyclonal immune complex of Fab from pooled Ferret sera at day 28 binding B/Washington HA after infection with B/Washington/02/2019
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-47799: Polyclonal immune complex of Fab from pooled Ferret sera at day 28 binding B/Washington NA after infection with B/Washington/02/2019
Method: EM (single particle) / Resolution: 20.0 Å

Source
  • Mustela putorius furo (domestic ferret)

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