Targeted isolation of diverse human protective broadly neutralizing antibodies against SARS-like viruses

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(6), P. 960 - 970

Published: June 1, 2022

Language: Английский

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A variant-proof SARS-CoV-2 vaccine targeting HR1 domain in S2 subunit of spike protein

Cell Research, Journal Year: 2022, Volume and Issue: 32(12), P. 1068 - 1085

Published: Nov. 10, 2022

Abstract The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy current vaccines and antibody therapeutics. This calls for variant-proof targeting more conserved regions S protein. Here, we designed a recombinant vaccine, HR121, HR1 domain S2 HR121 consisting HR1–linker1–HR2–linker2–HR1, is conformationally functionally analogous to present fusion intermediate conformation subunit. Immunization rabbits rhesus macaques elicited highly potent cross-neutralizing antibodies against its particularly Omicron sublineages. Vaccination achieved near-full protections prototype infection hACE2 transgenic mice, Syrian golden hamsters macaques, effective protection BA.2 hamsters. study demonstrates that promising candidate vaccine novel target application future variants.

Language: Английский

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Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Dec. 27, 2022

As SARS-CoV-2 Omicron and other variants of concern (VOCs) continue spreading worldwide, development antibodies vaccines to confer broad protective activity is a global priority. Here, we report on the identification special group nanobodies from immunized alpaca with potency against diverse VOCs including subvariants BA.1, BA.2 BA.4/5, SARS-CoV-1, major sarbecoviruses. Crystal structure analysis one representative nanobody, 3-2A2-4, discovers highly conserved epitope located between cryptic outer face receptor binding domain (RBD), distinctive ACE2 site. Cryo-EM biochemical evaluation reveal that 3-2A2-4 interferes structural alteration RBD required for binding. Passive delivery protects K18-hACE2 mice infection authentic Delta Omicron. Identification these unique will inform next generation antibody therapies design pan-sarbecovirus vaccines.

Language: Английский

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Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses

Cell Host & Microbe, Journal Year: 2022, Volume and Issue: 31(1), P. 97 - 111.e12

Published: Nov. 7, 2022

Humanity has faced three recent outbreaks of novel betacoronaviruses, emphasizing the need to develop approaches that broadly target coronaviruses. Here, we identify 55 monoclonal antibodies from COVID-19 convalescent donors bind diverse betacoronavirus spike proteins. Most targeted an S2 epitope included K814 residue and were non-neutralizing. However, 11 targeting stem helix neutralized betacoronaviruses different lineages. Eight in this group, including six broadest most potent neutralizers, encoded by IGHV1-46 IGKV3-20. Crystal structures class at 1.5-1.75-Å resolution revealed a conserved mode binding. COV89-22 SARS-CoV-2 variants concern Omicron BA.4/5 limited disease Syrian hamsters. Collectively, these findings IGHV1-46/IGKV3-20 neutralize but indicate constitute small fraction reactive antibody response after infection.

Language: Английский

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Protective neutralizing epitopes in SARS‐CoV‐2

Immunological Reviews, Journal Year: 2022, Volume and Issue: 310(1), P. 76 - 92

Published: May 22, 2022

Abstract The COVID‐19 pandemic has caused an unprecedented health crisis and economic burden worldwide. Its etiological agent SARS‐CoV‐2, a new virus in the coronavirus family, infected hundreds of millions people SARS‐CoV‐2 evolved over past 2 years to increase its transmissibility as well evade immunity established by previous infection vaccination. Nevertheless, strong immune responses can be elicited viral vaccination, which have proved protective against emergence variants, particularly with respect hospitalization or severe disease. Here, we review our current understanding how enters host cell system is able defend entry infection. Neutralizing antibodies are major component defense been extensively studied for variants. Structures these neutralizing provided valuable insights into epitopes that original ancestral variants emerged. molecular characterization epitope conservation resistance important design next‐generation vaccines antibody therapeutics.

Language: Английский

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