Sao-Fong Cheung, Crystal Fruehwirth, Alexander Paparoditis, Philipp Carl Georg Shen, Chen-Hsiang Foglierini, Mathilde Joyce, M. Gordon Leung, Kwanyee Piccoli, Luca Rawi, Reda Silacci-Fregni, Chiara Tsybovsky, Yaroslav Verardi, Raffaello Wang, Lingshu Wang, Shuishu Yang, Eun Sung Zhang, Baoshan Zhang, Yi Chuang, Gwo-Yu Corti, Davide Mascola, John R. Shapiro, Lawrence Kwong, Peter D. Lanzavecchia, Antonio Zhou, Tongqing 2020-09-01 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. application/pdf https://susi.usi.ch/global/documents/319378 https://n2t.net/ark:/12658/srd1319378 https://susi.usi.ch/documents/319378/files/Fruewirth_2020_cellrep.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2020.108088 info:eu-repo/semantics/altIdentifier/ark/12658/srd1319378 info:eu-repo/semantics/openAccess CC BY-NC-ND Cell reports. - 2020, vol. 32, no. 9, p. 12 p Influenza Hemagglutinin Multidonor antibody class Sialic acid-binding site Neutralizing antibodies Germline-reverted X-ray crystal structure Recurrent elication Elicitation frequency Vaccination info:eu-repo/classification/udc/61 Identification and structure of a multidonor class of head-directed influenza-neutralizing antibodies reveal the mechanism for its recurrent elicitation http://purl.org/coar/resource_type/c_6501