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TitlePotent and broadly neutralizing antibodies against sarbecoviruses induced by sequential COVID-19 vaccination.
Journal, issue, pagesCell Discov, Vol. 10, Issue 1, Page 14, Year 2024
Publish dateFeb 6, 2024
AuthorsXiaoyu Zhao / Tianyi Qiu / Xiner Huang / Qiyu Mao / Yajie Wang / Rui Qiao / Jiayan Li / Tiantian Mao / Yuan Wang / Yewei Cun / Caicui Wang / Cuiting Luo / Chaemin Yoon / Xun Wang / Chen Li / Yuchen Cui / Chaoyue Zhao / Minghui Li / Yanjia Chen / Guonan Cai / Wenye Geng / Zixin Hu / Jinglei Cao / Wenhong Zhang / Zhiwei Cao / Hin Chu / Lei Sun / Pengfei Wang /
PubMed AbstractThe current SARS-CoV-2 variants strikingly evade all authorized monoclonal antibodies and threaten the efficacy of serum-neutralizing activity elicited by vaccination or prior infection, urging the ...The current SARS-CoV-2 variants strikingly evade all authorized monoclonal antibodies and threaten the efficacy of serum-neutralizing activity elicited by vaccination or prior infection, urging the need to develop antivirals against SARS-CoV-2 and related sarbecoviruses. Here, we identified both potent and broadly neutralizing antibodies from a five-dose vaccinated donor who exhibited cross-reactive serum-neutralizing activity against diverse coronaviruses. Through single B-cell sorting and sequencing followed by a tailor-made computational pipeline, we successfully selected 86 antibodies with potential cross-neutralizing ability from 684 antibody sequences. Among them, PW5-570 potently neutralized all SARS-CoV-2 variants that arose prior to Omicron BA.5, and the other three could broadly neutralize all current SARS-CoV-2 variants of concern, SARS-CoV and their related sarbecoviruses (Pangolin-GD, RaTG13, WIV-1, and SHC014). Cryo-EM analysis demonstrates that these antibodies have diverse neutralization mechanisms, such as disassembling spike trimers, or binding to RBM or SD1 to affect ACE2 binding. In addition, prophylactic administration of these antibodies significantly protects nasal turbinate and lung infections against BA.1, XBB.1, and SARS-CoV viral challenge in golden Syrian hamsters, respectively. Importantly, post-exposure treatment with PW5-5 and PW5-535 also markedly protects against XBB.1 challenge in these models. This study reveals the potential utility of computational process to assist screening cross-reactive antibodies, as well as the potency of vaccine-induced broadly neutralizing antibodies against current SARS-CoV-2 variants and related sarbecoviruses, offering promising avenues for the development of broad therapeutic antibody drugs.
External linksCell Discov / PubMed:38320990 / PubMed Central
MethodsEM (single particle)
Resolution2.78 - 3.73 Å
Structure data

37139

8kdm

EMDB-37139, PDB-8kdm:
Structure of SARS-CoV Spike protein complexed with antibody PW5-5
Method: EM (single particle) / Resolution: 2.87 Å

37143

8kdr

EMDB-37143, PDB-8kdr:
The local refined map of SARS-CoV-2 XBB Variant Spike protein complexed with antibody PW5-535
Method: EM (single particle) / Resolution: 3.4 Å

37144

8kds

EMDB-37144, PDB-8kds:
Trimer state of SARS-CoV Spike protein complexed with antibody PW5-535
Method: EM (single particle) / Resolution: 3.05 Å

37145

8kdt

EMDB-37145, PDB-8kdt:
The local refined map of SARS-CoV Spike protein complexed with antibody PW5-5
Method: EM (single particle) / Resolution: 3.04 Å

37160

8kej

EMDB-37160, PDB-8kej:
Monomer state of SARS-CoV-2 XBB Variant Spike protein trimer complexed with antibody PW5-5
Method: EM (single particle) / Resolution: 3.73 Å

37161

8kek

EMDB-37161, PDB-8kek:
Monomer state of SARS-CoV Spike protein complexed with antibody PW5-535
Method: EM (single particle) / Resolution: 3.54 Å

37162

8keo

EMDB-37162, PDB-8keo:
Structure of SARS-CoV-2 Omicron BA.1 Spike complexed with antibody PW5-570
Method: EM (single particle) / Resolution: 2.78 Å

37163

8kep

EMDB-37163, PDB-8kep:
The local refined map of SARS-CoV-2 Omicron BA.1 Spike complexed with antibody PW5-570
Method: EM (single particle) / Resolution: 2.93 Å

37164

8keq

EMDB-37164, PDB-8keq:
State 1 of SARS-CoV-2 XBB Variant Spike protein trimer complexed with antibody PW5-5
Method: EM (single particle) / Resolution: 3.14 Å

37165

8ker

EMDB-37165, PDB-8ker:
Structure of SARS-CoV-2 XBB Variant Spike protein complexed with broadly neutralizing antibody PW5-535
Method: EM (single particle) / Resolution: 2.95 Å

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Antibody / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / IMMUNE SYSTEM/VIRAL PROTEIN / IMMUNE SYSTEM-VIRAL PROTEIN complex

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