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Publication Abstract from PubMed

Multidonor antibodies are of interest for vaccine design because they can in principle be elicited in the general population by a common set of immunogens. For influenza, multidonor antibodies have been observed against the hemagglutinin (HA) stem, but not the immunodominant HA head. Here, we identify and characterize a multidonor antibody class (LPAF-a class) targeting the HA head. This class exhibits potent viral entry inhibition against H1N1 A/California/04/2009 (CA09) virus. LPAF-a class antibodies derive from the HV2-70 gene and contain a "Tyr-Gly-Asp"-motif, which occludes the HA-sialic acid binding site as revealed by a co-crystal structure with HA. Both germline-reverted and mature LPAF antibodies potently neutralize CA09 virus and have nanomolar affinities for CA09 HA. Moreover, increased frequencies for LPFA-a class antibodies are observed in humans after a single vaccination. Overall, this work highlights the identification of a multidonor class of head-directed influenza-neutralizing antibodies and delineates the mechanism of their recurrent elicitation in humans.

Identification and Structure of a Multidonor Class of Head-Directed Influenza-Neutralizing Antibodies Reveal the Mechanism for Its Recurrent Elicitation.,Cheung CS, Fruehwirth A, Paparoditis PCG, Shen CH, Foglierini M, Joyce MG, Leung K, Piccoli L, Rawi R, Silacci-Fregni C, Tsybovsky Y, Verardi R, Wang L, Wang S, Yang ES, Zhang B, Zhang Y, Chuang GY, Corti D, Mascola JR, Shapiro L, Kwong PD, Lanzavecchia A, Zhou T Cell Rep. 2020 Sep 1;32(9):108088. doi: 10.1016/j.celrep.2020.108088. PMID:32877670^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.