Structure, Journal Year: 2024, Volume and Issue: 32(9), P. 1301 - 1321
Published: Sept. 1, 2024
Language: Английский
Cell, Journal Year: 2022, Volume and Issue: 185(14), P. 2422 - 2433.e13
Published: June 9, 2022
The Omicron lineage of SARS-CoV-2, which was first described in November 2021, spread rapidly to become globally dominant and has split into a number sublineages. BA.1 dominated the initial wave but been replaced by BA.2 many countries. Recent sequencing from South Africa's Gauteng region uncovered two new sublineages, BA.4 BA.5, are taking over locally, driving wave. BA.5 contain identical spike sequences, although closely related BA.2, they further mutations receptor-binding domain their spikes. Here, we study neutralization BA.4/5 using range vaccine naturally immune serum panels monoclonal antibodies. shows reduced individuals vaccinated with triple doses AstraZeneca or Pfizer compared BA.2. Furthermore, breakthrough infections, there are, likewise, significant reductions BA.4/5, raising possibility repeat infections.
Language: Английский
Citations
680
Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(3), P. 189 - 199
Published: Sept. 27, 2022
Language: Английский
Citations
286
The Lancet Infectious Diseases, Journal Year: 2022, Volume and Issue: 22(11), P. e311 - e326
Published: July 5, 2022
Language: Английский
Citations
220
Immunity, Journal Year: 2023, Volume and Issue: 56(3), P. 669 - 686.e7
Published: Feb. 16, 2023
Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against novel pandemic coronaviruses and more effectively respond SARS-CoV-2 variants. The emergence of Omicron subvariants illustrates limitations solely targeting receptor-binding domain (RBD) spike (S) protein. Here, we isolated a large panel (bnAbs) from recovered-vaccinated donors, which targets conserved S2 region in betacoronavirus fusion machinery. Select bnAbs showed broad vivo protection all three deadly betacoronaviruses, SARS-CoV-1, SARS-CoV-2, MERS-CoV, have spilled over into humans past two decades. Structural studies these delineated molecular basis for their reactivity revealed common antibody features targetable by vaccination strategies. These provide new insights opportunities antibody-based interventions pan-betacoronavirus vaccines.
Language: Английский
Citations
121
Microbiology Spectrum, Journal Year: 2022, Volume and Issue: 10(4)
Published: June 14, 2022
SARS-CoV-2 Omicron variants contain many mutations in its spike receptor-binding domain, the target of all authorized monoclonal antibodies (MAbs). Determining extent to which reduced MAb susceptibility is critical preventing and treating COVID-19. We systematically reviewed PubMed three preprint servers, last updated 11 April 2022, for vitro activity MAbs against variants. Fifty-one studies were eligible, including 50 containing BA.1 data 17 BA.2 data. The first two combinations, bamlanivimab/etesevimab casirivimab/imdevimab, largely inactive In 34 studies, sotrovimab displayed a median 4.0-fold (interquartile range [IQR]: 2.6 6.9) reduction BA.1, 12 it 17-fold (IQR: 13 30) BA.2. 15 combination cilgavimab/tixagevimab 86-fold 27 151) six 5.4-fold 3.7 eight BA.2, bebtelovimab no activity. Disparate results between assays common. For MAbs, 51/268 (19.0%) wild-type control 78/348 (22.4%) more than 4-fold below or above result that MAb. Highly disparate published indicate need improved test standardization interassay calibration. IMPORTANCE Monoclonal (MAbs) targeting protein are among most effective measures However, their domains, MAbs. Therefore, determining identified 51 reported main therapeutic advanced clinical development, individual combinations. estimated degree different marked loss underscores importance developing conserved regions spike. standardization.
Language: Английский
Citations
77
Drug Resistance Updates, Journal Year: 2022, Volume and Issue: 65, P. 100882 - 100882
Published: Oct. 3, 2022
Language: Английский
Citations
42
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
Citations
41
Cell Reports, Journal Year: 2023, Volume and Issue: 42(4), P. 112271 - 112271
Published: March 7, 2023
In November 2021, Omicron BA.1, containing a raft of new spike mutations, emerged and quickly spread globally. Intense selection pressure to escape the antibody response produced by vaccines or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection then led rapid succession sub-lineages with waves BA.2 BA.4/5 infection. Recently, many variants have such as BQ.1 XBB, which carry up 8 additional receptor-binding domain (RBD) amino acid substitutions compared BA.2. We describe panel 25 potent monoclonal antibodies (mAbs) generated from vaccinees suffering breakthrough infections. Epitope mapping shows mAb binding shifting 3 clusters, corresponding early-pandemic hotspots. The RBD mutations in recent map close these sites knock out severely down neutralization activity all but 1 mAb. This corresponds large falls titer vaccine BA.2, immune serum.
Language: Английский
Citations
39
Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(695)
Published: May 10, 2023
The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has placed an imperative on the development countermeasures provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent monoclonal antibodies (mAbs) neutralized multiple sarbecoviruses from macaques vaccinated with AS03-adjuvanted monovalent subunit vaccines. Longitudinal analysis revealed progressive accumulation somatic mutation in immunoglobulin genes antigen-specific memory B cells (MBCs) for at least 1 year after primary vaccination. Antibodies generated these MBCs 5 to 12 months displayed greater potency breadth relative those 1.4 months. Fifteen 338 (about 4.4%) isolated 6 showed BA.1, despite absence serum BA.1 neutralization. 25F9 20A7 authentic clade (SARS-CoV, WIV-1, SHC014, D614G, Pangolin-GD) vesicular stomatitis virus–pseudotyped 3 (BtKY72 PRD-0038). 27A12 neutralization all Omicron sublineages, including BA.2, BA.3, BA.4/5, BQ.1, BQ.1.1, XBB. Crystallography studies molecular basis through targeting conserved sites within RBD. Prophylactic 25F9, 20A7, was confirmed mice, administration particularly provided complete SARS-CoV-2, SARS-CoV, SHC014 challenge. These data underscore activity mAbs
Language: Английский
Citations
38
Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(24)
Published: June 5, 2023
Nanobodies bind a target antigen with kinetic profile similar to conventional antibody, but exist as single heavy chain domain that can be readily multimerized engage via multiple interactions. Presently, most nanobodies are produced by immunizing camelids; however, platforms for animal-free production growing in popularity. Here, we describe the development of fully synthetic nanobody library based on an engineered human V
Language: Английский
Citations
28