tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Alexander Fruehwirth[SUP] 2 [/SUP], Philipp Carl Georg Paparoditis[SUP] 2 [/SUP], Chen-Hsiang Shen[SUP] 1 [/SUP], Mathilde Foglierini[SUP] 2 [/SUP], M Gordon Joyce[SUP] 1 [/SUP], Kwanyee Leung[SUP] 1 [/SUP], Luca Piccoli[SUP] 2 [/SUP], Reda Rawi[SUP] 1 [/SUP], Chiara Silacci-Fregni[SUP] 2 [/SUP], Yaroslav Tsybovsky[SUP] 3 [/SUP], Raffaello Verardi[SUP] 1 [/SUP], Lingshu Wang[SUP] 1 [/SUP], Shuishu Wang[SUP] 1 [/SUP], Eun Sung Yang[SUP] 1 [/SUP], Baoshan Zhang[SUP] 1 [/SUP], Yi Zhang[SUP] 1 [/SUP], Gwo-Yu Chuang[SUP] 1 [/SUP], Davide Corti[SUP] 2 [/SUP], John R Mascola[SUP] 1 [/SUP], Lawrence Shapiro[SUP] 4 [/SUP], Peter D Kwong[SUP] 5 [/SUP], Antonio Lanzavecchia[SUP] 6 [/SUP], Tongqing Zhou[SUP] 7 [/SUP]
Affiliations
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.
. 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[SUP] 1 [/SUP], Alexander Fruehwirth[SUP] 2 [/SUP], Philipp Carl Georg Paparoditis[SUP] 2 [/SUP], Chen-Hsiang Shen[SUP] 1 [/SUP], Mathilde Foglierini[SUP] 2 [/SUP], M Gordon Joyce[SUP] 1 [/SUP], Kwanyee Leung[SUP] 1 [/SUP], Luca Piccoli[SUP] 2 [/SUP], Reda Rawi[SUP] 1 [/SUP], Chiara Silacci-Fregni[SUP] 2 [/SUP], Yaroslav Tsybovsky[SUP] 3 [/SUP], Raffaello Verardi[SUP] 1 [/SUP], Lingshu Wang[SUP] 1 [/SUP], Shuishu Wang[SUP] 1 [/SUP], Eun Sung Yang[SUP] 1 [/SUP], Baoshan Zhang[SUP] 1 [/SUP], Yi Zhang[SUP] 1 [/SUP], Gwo-Yu Chuang[SUP] 1 [/SUP], Davide Corti[SUP] 2 [/SUP], John R Mascola[SUP] 1 [/SUP], Lawrence Shapiro[SUP] 4 [/SUP], Peter D Kwong[SUP] 5 [/SUP], Antonio Lanzavecchia[SUP] 6 [/SUP], Tongqing Zhou[SUP] 7 [/SUP]
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.