Cell Rep
. 2020 Sep 1;32(9):108088.
doi: 10.1016/j.celrep.2020.108088.
Identification and Structure of a Multidonor Class of Head-Directed Influenza-Neutralizing Antibodies Reveal the Mechanism for Its Recurrent Elicitation
Crystal Sao-Fong Cheung 1 , Alexander Fruehwirth 2 , Philipp Carl Georg Paparoditis 2 , Chen-Hsiang Shen 1 , Mathilde Foglierini 2 , M Gordon Joyce 1 , Kwanyee Leung 1 , Luca Piccoli 2 , Reda Rawi 1 , Chiara Silacci-Fregni 2 , Yaroslav Tsybovsky 3 , Raffaello Verardi 1 , Lingshu Wang 1 , Shuishu Wang 1 , Eun Sung Yang 1 , Baoshan Zhang 1 , Yi Zhang 1 , Gwo-Yu Chuang 1 , Davide Corti 2 , John R Mascola 1 , Lawrence Shapiro 4 , Peter D Kwong 5 , Antonio Lanzavecchia 6 , Tongqing Zhou 7
Affiliations
- PMID: 32877670
- DOI: 10.1016/j.celrep.2020.108088
Abstract
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.
Keywords: Influenza; X-ray crystal structure; elicitation frequency; germline-reverted; hemagglutinin; multidonor antibody class; neutralizing antibodies; recurrent elication; sialic acid-binding site; vaccination.