Identification and structure of a multidonor class of head-directed influenza-neutralizing antibodies reveal the mechanism for its recurrent elicitation

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

doi:10.1016/j.celrep.2020.108088

Back

Journal article

Identification and structure of a multidonor class of head-directed influenza-neutralizing antibodies reveal the mechanism for its recurrent elicitation

Sao-Fong Cheung, Crystal Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA
Fruehwirth, Alexander Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Paparoditis, Philipp Carl Georg Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Shen, Chen-Hsiang Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA
Foglierini, Mathilde Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Joyce, M. Gordon Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA
Leung, Kwanyee Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA
Piccoli, Luca Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Rawi, Reda Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA
Silacci-Fregni, Chiara Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Tsybovsky, Yaroslav Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, USA
Verardi, Raffaello Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA
Wang, Lingshu Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA
Wang, Shuishu Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA
Yang, Eun Sung Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA
Zhang, Baoshan Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA
Zhang, Yi Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA
Chuang, Gwo-Yu Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA
Corti, Davide Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Mascola, John R. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA
Shapiro, Lawrence Zuckerman Mind Brain Behavior Institute, Columbia University, New York, USA - Department of Biochemistry and Molecular Biophysics, Columbia University, New York, USA
Kwong, Peter D. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA - Department of Biochemistry and Molecular Biophysics, Columbia University, New York, USA
Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Zhou, Tongqing Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA

01.09.2020

Published in:

Cell reports. - 2020, vol. 32, no. 9, p. 12 p

English 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.

Language