ETIDIOH - NEW

Highlights -- Both NA-specific antibodies and memory B cells are detected in healthy adults -- NA broad-inhibition monoclonal antibodies are derived from classical memory B cells -- Broad inhibition monoclonal antibodies target the NA conserved enzymatic epitopes -- NA broad-inhibition antibodies protect mice against H1N1 and H5N1- clade 2.3.4.4b Summary Identifying broadly reactive B precursor cells and conserved epitopes is crucial for developing a universal flu vaccine . In this study, using influenza neuraminidase (NA) mutant probes , we find that human pre-existing NA-specific memory B cells (MBCs) account for ∼0.25% of total MBCs, which are heterogeneous and dominated by class-unswitched MBCs. In addition, we identify three NA broad-inhibition monoclonal antibodies (mAbs) (BImAbs) that block the activity of NA derived from different influenza strains, including the recent cow H5N1. The cryoelectron microscopy (cryo-EM) structure shows that the BImAb targets the conserved NA enzym...

ABSTRACT The highly pathogenic avian influenza virus A(H5N1) clade 2.3.4.4b has caused a human outbreak in North America since March 2024 . Here, we conducted a serosurveillance study to determine the risk of A(H5N1) clade 2.3.4.4b (2024 cattle H5N1 ) to general population . In the initial screening of 180 serum specimens encompassing all age groups , 2.2% (4/180) had detectable neutralizing antibody (nAb) titers against 2024 cattle H5N1, with all collected from older adults aged ≥60 years old . Further screening showed that 5.0% (15/300) of adults aged ≥70 years old had detectable nAb titers against the 2024 cattle H5N1. All serum specimens with nAb titer of ≥40 had detectable HI titer, and there was a positive correlation between nAb titer and HA binding (r=0.3311, 95% confidence interval 0.2264 to 0.4283; P<0.0001). The nAb titer against seasonal H1N1 virus was 3.9-fold higher for patients with detectable H5N1 nAb than those without (geometric mean titer: 108.5 [95% CI 56.3-209.1...

ABSTRACT Frequent recent spillovers of subtype H5N1 clade 2.3.4.4b highly pathogenic avian influenza (HPAI) virus into poultry and mammals , especially dairy cattle, including several human cases , increased concerns over a possible future pandemic . Here, we performed an analysis of epitope data curated in the Immune Epitope Database (IEDB). We found that the patterns of immunodominance of seasonal influenza viruses circulating in humans and H5N1 are similar . We further conclude that a significant fraction of the T-cell epitopes is conserved at a level associated with cross-reactivity between avian and seasonal sequences, and we further experimentally demonstrate extensive cross-reactivity in the most dominant T-cell epitopes curated in the IEDB. Based on these observations, and the overall similarity of the neuraminidase (NA) N1 subtype encoded in both HPAI and seasonal H1N1 influenza virus as well as cross-reactive group 1 HA stalk-reactive antibodies, we expect that a degree of pr...