A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants

Shan, Sicong; Mok, Chee Keng; Lei, Jun; Li, Jizhou; Yang, Ziqing; Wang, Ruoke; Cheng, Lin; Aw, Zhen Qin; Shi, Xuanling; Yu, Jinfang; Zhang, Qi; Wang, Jianbin; Wang, Xinquan; Chu, Justin Jang Hann; Zhang, Linqi

doi:10.3389/fimmu.2021.766821

Cited by 16 publications

(14 citation statements)

References 56 publications

(103 reference statements)

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“…Since RBS‐C is exposed on the spike surface regardless of RBD conformation, antibodies targeting RBS‐C, such as AZD1061, C104, P36‐5D2, BG1‐24, BG7‐20, and N‐612‐017, can usually bind RBD in both up and down states. 169 , 173 , 209 , 210 RBS‐C antibodies, such as BG1‐24 and BG7‐20, can bind the RBD in down state while interacting with glycans on NTD and a neighboring “up”‐RBD. 173 However, some RBS‐C antibodies, such as COVOX‐58, only bind RBD in the down state due to its close proximity to NTD.…”

Section: Neutralizing Epitopes On Sars‐cov‐2 Spikementioning

confidence: 99%

“… 148 , 168 , 173 , 212 Notwithstanding that RBS‐C antibodies are also sensitive to mutations in VOCs at E484 and L452, broad neutralization against several variants of concern has been observed in a few antibodies. 204 , 209 …”

Section: Neutralizing Epitopes On Sars‐cov‐2 Spikementioning

confidence: 99%

“…RBS‐C antibodies can also be very potent, for example 1‐57 (8 ng/mL), β38 (11 ng/mL), S2D106 (7 ng/mL) and BG1‐24 (2 ng/mL) 148,168,173,212 . Notwithstanding that RBS‐C antibodies are also sensitive to mutations in VOCs at E484 and L452, broad neutralization against several variants of concern has been observed in a few antibodies 204,209 …”

Section: Neutralizing Epitopes On Sars‐cov‐2 Spikementioning

confidence: 99%

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Protective neutralizing epitopes in SARS‐CoV‐2

Liu

Wilson

2022

Immunological Reviews

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

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Section: Neutralizing Epitopes On Sars‐cov‐2 Spikementioning

confidence: 99%

Section: Neutralizing Epitopes On Sars‐cov‐2 Spikementioning

confidence: 99%

Section: Neutralizing Epitopes On Sars‐cov‐2 Spikementioning

confidence: 99%

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Protective neutralizing epitopes in SARS‐CoV‐2

Liu

Wilson

2022

Immunological Reviews

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“…We next studied the protective potential of 3-2A2-4 against infection of authentic Omicron and Delta variants in a K18-hACE2 mouse model of SARS-CoV-2 infection, as previously described (Figure. 5a) 48 . Specifically, the mice were intraperitoneally administered with 3-2A2-4 at a dose of 10 mg/kg body weight 24 hours prior to intranasal challenge with 1.7×10 3 plaque-forming units (PFU) of authentic SARS-CoV-2 Omicron or 10 3 PFU of SARS-CoV-2 Delta.…”

Section: Resultsmentioning

confidence: 99%

Broadly neutralizing and protective nanobodies against diverse sarbecoviruses

Ren

et al. 2022

Preprint

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As SARS-CoV-2 Omicron and other variants of concern continue spreading around the world, development of antibodies and vaccines to confer broad and protective activity is a global priority. Here, we report on the identification of a special group of nanobodies from immunized alpaca with exceptional breadth and potency against diverse sarbecoviruses including SARS-CoV-1, Omicron BA.1, and BA.2. Crystal structure analysis of one representative nanobody, 3-2A2-4, revealed a highly conserved epitope between the cryptic and the outer face of the receptor binding domain (RBD). The epitope is readily accessible regardless of RBD in up or down conformation and distinctive from the receptor ACE2 binding site. Passive delivery of 3-2A2-4 protected K18-hACE2 mice from infection of authentic SARS-CoV-2 Delta and Omicron. This group of nanobodies and the epitope identified should provide invaluable reference for the development of next generation antibody therapies and vaccines against wide varieties of SARS-CoV-2 infection and beyond.

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“…Neutralization activity of monoclonal antibodies against SARS-CoV-2 pseudoviruses were assayed as previously described 67 . 50 μL serial dilutions of monoclonal antibodies (mAbs) were added into 96-well plates.…”

Section: Virus Neutralization Assaymentioning

confidence: 99%

Structural basis of a two-antibody cocktail exhibiting highly potent and broadly neutralizing activities against SARS-CoV-2 variants including diverse Omicron sublineages

Pan²,

Yin

et al. 2022

Preprint

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SARS-CoV-2 variants of concern (VOCs), especially the latest Omicron, have exhibited severe antibody evasion. Broadly neutralizing antibodies with high potency against Omicron are urgently needed for understanding working mechanisms and developing therapeutic agents. In this study, we characterized previously reported F61, which was isolated from convalescent patients infected with prototype SARS-CoV-2, as a broadly neutralizing antibody against all VOCs including Omicron BA.1, BA.1.1, BA.2, BA.3 and BA.4 sublineages by utilizing antigen binding and cell infection assays. We also identified and characterized another broadly neutralizing antibody D2 with epitope distinct from that of F61. More importantly, we showed that a combination of F61 with D2 exhibited synergy in neutralization and protecting mice from SARS-CoV-2 Delta and Omicron BA.1 variants. Cryo-EM structures of the spike-F61 and spike-D2 binary complexes revealed the distinct epitopes of F61 and D2 at atomic level and the structural basis for neutralization. Cryo-EM structure of the Omicron-spike-F61-D2 ternary complex provides further structural insights into the synergy between F61 and D2. These results collectively indicated F61 and F61-D2 cocktail as promising therapeutic antibodies for combating SARS-CoV-2 variants including diverse Omicron sublineages.

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A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants

Cited by 16 publications

References 56 publications

Protective neutralizing epitopes in SARS‐CoV‐2

Protective neutralizing epitopes in SARS‐CoV‐2

Broadly neutralizing and protective nanobodies against diverse sarbecoviruses

Structural basis of a two-antibody cocktail exhibiting highly potent and broadly neutralizing activities against SARS-CoV-2 variants including diverse Omicron sublineages

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