Native human monoclonal antibodies with potent cross-lineage neutralization of influenza B viruses [PublishAheadOfPrint]

Although antibodies that effectively neutralize a broad set of influenza viruses exist in the human antibody repertoire, they are rare. We used a single cell screening technology to identify rare monoclonal antibodies (mAbs) that recognized a broad set of influenza B viruses (IBV). The screen yielded 23 mAbs with diverse germ line origins that recognized hemagglutinins (HAs) derived from influenza strains of both the Yamagata and Victoria lineages of IBV. Of the 23 mAbs, three exhibited low expression in a transient transfection system, four were neutralizers that bound to the HA head region, eleven were stalk-binding non-neutralizers, and five were stalk-binding neutralizers with four of these five representing unique antibody sequences. Of these four unique stalk-binding neutralizing mAbs, all were broadly reactive and neutralizing against a panel of multiple strains spanning both IBV lineages as well as highly effective in treating lethal IBV infections in mice at both 24 and 72 hours post-infection. The mAbs in this group were thermostable and bound different epitopes in the highly conserved HA stalk region. These characteristics suggest these mAbs are suitable for consideration as candidates for clinical studies to address effectiveness in treating of IBV infected patients.

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