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Identification of a broad-inhibition #influenza #neuraminidase #antibody from pre-existing memory B cells

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By G.M.

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 enzymatic pocket and a separate epitope in the neighboring NA monomer. Furthermore, the NA BImAbs protect mice from the lethal challenge of the human pandemic H1N1 and H5N1. Our work demonstrates that the NA broad-inhibition precursor MBCs exist in healthy adults and could be targeted by the NA-based universal flu vaccine.

Source: Cell Host Microbe, https://www.sciencedirect.com/science/article/abs/pii/S1931312824004670?via%3Dihub

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