Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus
Although Rhinolophus bats harbor diverse clade 3 sarbecoviruses, the structural determinants of receptor tropism along with the antigenicity of their spike (S) glycoproteins remain uncharacterized. Here, we show that the African Rhinolophus bat clade 3 sarbecovirus PRD-0038 S has a broad angiotensin...
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| Veröffentlicht in: | Cell host & microbe 2023-12, Vol.31 (12), p.1961-1973.e11 |
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| container_end_page | 1973.e11 |
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| container_issue | 12 |
| container_start_page | 1961 |
| container_title | Cell host & microbe |
| container_volume | 31 |
| creator | Lee, Jimin Zepeda, Samantha K Park, Young-Jun Taylor, Ashley L Quispe, Joel Stewart, Cameron Leaf, Elizabeth M Treichel, Catherine Corti, Davide King, Neil P Starr, Tyler N Veesler, David |
| description | Although Rhinolophus bats harbor diverse clade 3 sarbecoviruses, the structural determinants of receptor tropism along with the antigenicity of their spike (S) glycoproteins remain uncharacterized. Here, we show that the African Rhinolophus bat clade 3 sarbecovirus PRD-0038 S has a broad angiotensin-converting enzyme 2 (ACE2) usage and that receptor-binding domain (RBD) mutations further expand receptor promiscuity and enable human ACE2 utilization. We determine a cryo-EM structure of the PRD-0038 RBD bound to Rhinolophus alcyone ACE2, explaining receptor tropism and highlighting differences with SARS-CoV-1 and SARS-CoV-2. Characterization of PRD-0038 S using cryo-EM and monoclonal antibody reactivity reveals its distinct antigenicity relative to SARS-CoV-2 and identifies PRD-0038 cross-neutralizing antibodies for pandemic preparedness. PRD-0038 S vaccination elicits greater titers of antibodies cross-reacting with vaccine-mismatched clade 2 and clade 1a sarbecoviruses compared with SARS-CoV-2 S due to broader antigenic targeting, motivating the inclusion of clade 3 antigens in next-generation vaccines for enhanced resilience to viral evolution. |
| doi_str_mv | 10.1016/j.chom.2023.10.018 |
| format | Article |
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PRD-0038 S vaccination elicits greater titers of antibodies cross-reacting with vaccine-mismatched clade 2 and clade 1a sarbecoviruses compared with SARS-CoV-2 S due to broader antigenic targeting, motivating the inclusion of clade 3 antigens in next-generation vaccines for enhanced resilience to viral evolution.</description><subject>Angiotensin-Converting Enzyme 2</subject><subject>Animals</subject><subject>Antibodies, Viral</subject><subject>Chiroptera</subject><subject>Humans</subject><subject>SARS-CoV-2 - genetics</subject><subject>Severe acute respiratory syndrome-related coronavirus</subject><subject>Spike Glycoprotein, Coronavirus</subject><subject>Tropism</subject><issn>1931-3128</issn><issn>1934-6069</issn><issn>1934-6069</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkE1PwzAMhiME4vsPcEA5cumwmzZtTggmviQkLnCOstQdmdpmJC3S_j0tAwQnW_br1_bD2BnCDAHl5Wpm33w7SyEVY2EGWO6wQ1QiSyRItfuVYyIwLQ_YUYwrgDyHAvfZgShUOfbSQza_Cd5UPJClde8D74Nfu9hy01Xcte3Q-SV1zrp-w33NDbeNqYgLHk1YkPUfLgzxhO3Vpol0-h2P2evd7cv8IXl6vn-cXz8lNgPRJ8oKyiqVi9wsALJiUWTCgqyxwFpSTTQKsBQZ2LSwmawNEpQgjbKocjU-ecyutr7rYdFSZanrg2n0OrjWhI32xun_nc696aX_0AgKRS4nh4tvh-DfB4q9bl201DSmIz9EnZYqlRLKAkdpupXa4GMMVP_uQdATfr3SE3494Z9qI_5x6Pzvhb8jP7zFJ3U8glo</recordid><startdate>20231213</startdate><enddate>20231213</enddate><creator>Lee, Jimin</creator><creator>Zepeda, Samantha K</creator><creator>Park, Young-Jun</creator><creator>Taylor, Ashley L</creator><creator>Quispe, Joel</creator><creator>Stewart, Cameron</creator><creator>Leaf, Elizabeth M</creator><creator>Treichel, Catherine</creator><creator>Corti, Davide</creator><creator>King, Neil P</creator><creator>Starr, Tyler N</creator><creator>Veesler, David</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6019-8675</orcidid></search><sort><creationdate>20231213</creationdate><title>Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus</title><author>Lee, Jimin ; 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| identifier | ISSN: 1931-3128 |
| ispartof | Cell host & microbe, 2023-12, Vol.31 (12), p.1961-1973.e11 |
| issn | 1931-3128 1934-6069 1934-6069 |
| language | eng |
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| source | MEDLINE; Cell Press Free Archives; ScienceDirect Journals (5 years ago - present); EZB-FREE-00999 freely available EZB journals |
| subjects | Angiotensin-Converting Enzyme 2 Animals Antibodies, Viral Chiroptera Humans SARS-CoV-2 - genetics Severe acute respiratory syndrome-related coronavirus Spike Glycoprotein, Coronavirus Tropism |
| title | Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus |
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