tetano
Editor, Senior Moderator
Structure
. 2022 Jul 12;S0969-2126(22)00235-0.
doi: 10.1016/j.str.2022.06.004. Online ahead of print.
Vaccine-elicited murine antibody WS6 neutralizes diverse beta-coronaviruses by recognizing a helical stem supersite of vulnerability
Wei Shi[SUP] 1 [/SUP], Lingshu Wang[SUP] 1 [/SUP], Tongqing Zhou[SUP] 1 [/SUP], Mallika Sastry[SUP] 1 [/SUP], Eun Sung Yang[SUP] 1 [/SUP], Yi Zhang[SUP] 1 [/SUP], Man Chen[SUP] 1 [/SUP], Xuejun Chen[SUP] 1 [/SUP], Misook Choe[SUP] 1 [/SUP], Adrian Creanga[SUP] 1 [/SUP], Kwan Leung[SUP] 1 [/SUP], Adam S Olia[SUP] 1 [/SUP], Amarendra Pegu[SUP] 1 [/SUP], Reda Rawi[SUP] 1 [/SUP], Arne Schön[SUP] 2 [/SUP], Chen-Hsiang Shen[SUP] 1 [/SUP], Erik-Stephane D Stancofski[SUP] 1 [/SUP], Chloe Adrienna Talana[SUP] 1 [/SUP], I-Ting Teng[SUP] 1 [/SUP], Shuishu Wang[SUP] 1 [/SUP], Kizzmekia S Corbett[SUP] 1 [/SUP], Yaroslav Tsybovsky[SUP] 3 [/SUP], John R Mascola[SUP] 4 [/SUP], Peter D Kwong[SUP] 5 [/SUP]
Affiliations
Abstract
Immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike elicits diverse antibodies, but it is unclear if any of the antibodies can neutralize broadly against other beta-coronaviruses. Here, we report antibody WS6 from a mouse immunized with mRNA encoding the SARS-CoV-2 spike. WS6 bound diverse beta-coronavirus spikes and neutralized SARS-CoV-2 variants, SARS-CoV, and related sarbecoviruses. Epitope mapping revealed WS6 to target a region in the S2 subunit, which was conserved among SARS-CoV-2, Middle East respiratory syndrome (MERS)-CoV, and hCoV-OC43. The crystal structure at 2 Å resolution of WS6 revealed recognition to center on a conserved S2 helix, which was occluded in both pre- and post-fusion spike conformations. Structural and neutralization analyses indicated WS6 to neutralize by inhibiting fusion and post-viral attachment. Comparison of WS6 with other recently identified antibodies that broadly neutralize beta-coronaviruses indicated a stem-helical supersite-centered on hydrophobic residues Phe1148, Leu1152, Tyr1155, and Phe1156-to be a promising target for vaccine design.
Keywords: COVID-19; S2-directed antibody; SARS-CoV-2; beta-coronavirus; broadly neutralizing antibody; crystal structure; vaccine design.
. 2022 Jul 12;S0969-2126(22)00235-0.
doi: 10.1016/j.str.2022.06.004. Online ahead of print.
Vaccine-elicited murine antibody WS6 neutralizes diverse beta-coronaviruses by recognizing a helical stem supersite of vulnerability
Wei Shi[SUP] 1 [/SUP], Lingshu Wang[SUP] 1 [/SUP], Tongqing Zhou[SUP] 1 [/SUP], Mallika Sastry[SUP] 1 [/SUP], Eun Sung Yang[SUP] 1 [/SUP], Yi Zhang[SUP] 1 [/SUP], Man Chen[SUP] 1 [/SUP], Xuejun Chen[SUP] 1 [/SUP], Misook Choe[SUP] 1 [/SUP], Adrian Creanga[SUP] 1 [/SUP], Kwan Leung[SUP] 1 [/SUP], Adam S Olia[SUP] 1 [/SUP], Amarendra Pegu[SUP] 1 [/SUP], Reda Rawi[SUP] 1 [/SUP], Arne Schön[SUP] 2 [/SUP], Chen-Hsiang Shen[SUP] 1 [/SUP], Erik-Stephane D Stancofski[SUP] 1 [/SUP], Chloe Adrienna Talana[SUP] 1 [/SUP], I-Ting Teng[SUP] 1 [/SUP], Shuishu Wang[SUP] 1 [/SUP], Kizzmekia S Corbett[SUP] 1 [/SUP], Yaroslav Tsybovsky[SUP] 3 [/SUP], John R Mascola[SUP] 4 [/SUP], Peter D Kwong[SUP] 5 [/SUP]
Affiliations
- PMID: 35841885
- PMCID: PMC9284671
- DOI: 10.1016/j.str.2022.06.004
Abstract
Immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike elicits diverse antibodies, but it is unclear if any of the antibodies can neutralize broadly against other beta-coronaviruses. Here, we report antibody WS6 from a mouse immunized with mRNA encoding the SARS-CoV-2 spike. WS6 bound diverse beta-coronavirus spikes and neutralized SARS-CoV-2 variants, SARS-CoV, and related sarbecoviruses. Epitope mapping revealed WS6 to target a region in the S2 subunit, which was conserved among SARS-CoV-2, Middle East respiratory syndrome (MERS)-CoV, and hCoV-OC43. The crystal structure at 2 Å resolution of WS6 revealed recognition to center on a conserved S2 helix, which was occluded in both pre- and post-fusion spike conformations. Structural and neutralization analyses indicated WS6 to neutralize by inhibiting fusion and post-viral attachment. Comparison of WS6 with other recently identified antibodies that broadly neutralize beta-coronaviruses indicated a stem-helical supersite-centered on hydrophobic residues Phe1148, Leu1152, Tyr1155, and Phe1156-to be a promising target for vaccine design.
Keywords: COVID-19; S2-directed antibody; SARS-CoV-2; beta-coronavirus; broadly neutralizing antibody; crystal structure; vaccine design.