Broadly Neutralizing Antibodies Against Conserved Epitopes of the Hemagglutinin Head are Robustly Recalled by a Novel H1N1 Virus
60 Pages Posted: 24 Nov 2020 Publication Status: Review CompleteMore...
Broadly neutralizing antibodies are critical for protection against drifted and novel influenza viruses. Here, we reveal humans have pre-existing immunity against two broadly neutralizing epitopes of the HA head: the lateral patch and receptor-binding site (RBS). Monoclonal antibodies generated against these epitopes are broadly neutralizing against 40+ years of H1N1 evolution and provide potent protection in vivo. First exposure to the novel 2009 pandemic H1N1 virus recalls memory B cells that target the conserved RBS and lateral patch epitopes. We identified unique repertoire, structural, and binding features of lateral patch and RBS binding antibodies including a lateral patch binding motif shared across subjects. Together, our data indicate that the conserved RBS and lateral patch epitopes are readily targeted by the human memory B cell pool and that universal vaccine strategies should aim to drive antibodies against both conserved head and stalk domain epitopes.
Keywords: H1N1; hemagglutinin head; lateral patch; receptor-binding site; broadly neutralizing antibodies
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