A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses

Wang, Pengfei; Casner, Ryan G; Nair, Manoj S.; Yu, Jian; Guo, Yicheng; Wang, Maple; Chan, Jasper Fuk‐Woo; Cerutti, Gabriele; Iketani, Sho; Liu, Lihong; Sheng, Zizhang; Chen, Zhiwei; Yuen, Kwok‐Yung; Kwong, Peter D.; Huang, Yaoxing; Shapiro, Lawrence; Ho, David D.

doi:10.1080/22221751.2021.2011623

Cited by 37 publications

(40 citation statements)

References 41 publications

(56 reference statements)

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“…The only approved antibody that retained its neutralizing activity was S309, but still had a 7-fold reduction compared to WT ( Figure 2 , left panel). We further tested some other RBD-directed mAbs of interest, including ADG-2 [ 16 ], which is now under development by Adagio Therapeutics, and four more antibodies from our own collection, including 1–20 [ 17 ], 2–15 [ 17 ], 2–7 [ 17 ], and 2–36 [ 17 , 18 ], belong to class 1–4, respectively. The inability of these RBD mAbs to match the risk posed by Omicron was again apparent since all five mAbs tested lost their neutralizing activity, either completely (1–20, 2–15, and 2–7), or partially (ADG-2 and 2-36) ( Figure 2 , middle panel).…”

Section: Resultsmentioning

confidence: 99%

Homologous or heterologous booster of inactivated vaccine reduces SARS-CoV-2 Omicron variant escape from neutralizing antibodies

Wang

Zhao

Song

et al. 2022

Emerging Microbes & Infections

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122

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The massive and rapid transmission of SARS-CoV-2 has led to the emergence of several viral variants of concern (VOCs), with the most recent one, B.1.1.529 (Omicron), which accumulated a large number of spike mutations, raising the specter that this newly identified variant may escape from the currently available vaccines and therapeutic antibodies. Using VSV-based pseudovirus, we found that Omicron variant is markedly resistant to neutralization of sera from convalescents or individuals vaccinated by two doses of inactivated whole-virion vaccines (BBIBP-CorV). However, a homologous inactivated vaccine booster or a heterologous booster with protein subunit vaccine (ZF2001) significantly increased neutralization titers to both WT and Omicron variant. Moreover, at day 14 post the third dose, neutralizing antibody titer reduction for Omicron was less than that for convalescents or individuals who had only two doses of the vaccine, indicating that a homologous or heterologous booster can reduce the Omicron escape from neutralizing. In addition, we tested a panel of 17 SARS-CoV-2 monoclonal antibodies (mAbs). Omicron resists seven of eight authorized/approved mAbs, as well as most of the other mAbs targeting distinct epitopes on RBD and NTD. Taken together, our results suggest the urgency to push forward the booster vaccination to combat the emerging SARS-CoV-2 variants.

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Section: Resultsmentioning

confidence: 99%

Homologous or heterologous booster of inactivated vaccine reduces SARS-CoV-2 Omicron variant escape from neutralizing antibodies

Wang

Zhao

Song

et al. 2022

Emerging Microbes & Infections

Self Cite

122

111

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“…1B ). Epitope mapping by competition enzyme-linked immunosorbent assay (ELISA) was carried out on these three antibodies, along with a panel of nine RBD-specific mAbs reported to have breadth against sarbecoviruses, including DH1047 ( 8 ), S2X259 ( 9 ), REGN10985 ( 10 ), ADG-2 ( 11 ), 2-36 ( 12 ), COVA1-16 ( 13 ), CR3022 ( 14 ), S2H97 ( 15 ), and S309, also known as sotrovimab ( 16 ). 10-40, 10-28, and 11-11 fell into one competition group with seven other mAbs ( Fig.…”

Section: Resultsmentioning

confidence: 99%

An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses

et al. 2022

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The devastation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptor-binding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses, suggesting that 10-40 is a promising agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well-conserved among sarbecoviruses, but also uncovered a distinct antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine.

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“… 22 ), Fab2-36 (ref. 23 ) and P2B-2F6 (ref. 24 ) were produced in 293-6E cells (National Research Council of Canada) by co-transfection of heavy and light chain expression plasmids using 25 kDa branched polyethylenimine (Sigma-Aldrich, cat.…”

Section: Methodsmentioning

confidence: 99%

mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant

Gruell

Vanshylla

Tober‐Lau

et al. 2022

Nat Med

371

229

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The Omicron variant of SARS-CoV-2 is causing a rapid increase in infections across the globe. This new variant of concern carries an unusually high number of mutations in key epitopes of neutralizing antibodies on the viral spike glycoprotein, suggesting potential immune evasion. Here we assessed serum neutralizing capacity in longitudinal cohorts of vaccinated and convalescent individuals, as well as monoclonal antibody activity against Omicron using pseudovirus neutralization assays. We report a near-complete lack of neutralizing activity against Omicron in polyclonal sera from individuals vaccinated with two doses of the BNT162b2 COVID-19 vaccine and from convalescent individuals, as well as resistance to different monoclonal antibodies in clinical use. However, mRNA booster immunizations in vaccinated and convalescent individuals resulted in a significant increase of serum neutralizing activity against Omicron. This study demonstrates that booster immunizations can critically improve the humoral immune response against the Omicron variant.

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A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses

Cited by 37 publications

References 41 publications

Homologous or heterologous booster of inactivated vaccine reduces SARS-CoV-2 Omicron variant escape from neutralizing antibodies

Homologous or heterologous booster of inactivated vaccine reduces SARS-CoV-2 Omicron variant escape from neutralizing antibodies

An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses

mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant

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