Cell Res
 2020
DOI: 10.1038/s41422-020-00444-y
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Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection

Hangping Yao
1
,
Yao Sun
2
,
Yong‐Qiang Deng
3
et al.

Abstract: Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal mode… Show more

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Cited by 95 publications

(90 citation statements)
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“…According to our analysis, H014 interactions with conserved positions F377, C379, and S383 located away from the RBM region could be important for binding and modulation of the enhanced cross-neutralization activities. These results are also in accordance with the recent structure–functional investigation of the SARS-CoV-2 S complex with H014 and P17 forming a two-antibody cocktail with synergistic neutralization achieved by simultaneously binding to distinct RBD epitopes, where H014 strongly binds to a highly conserved patch across SARS-CoV and SARS-CoV-2, while P17 targets a SARS-CoV-2-specific patch . According to this illuminating experimental study, H014 binding to conserved hotspots F377, C379, Y380, S383, and P384 is critical to promote synergistic neutralization together with the P17 antibody by acting as a shield of the S1 region and blocking the SARS-CoV-2-RBD interactions with host cellular receptors.…”
Section: Resultssupporting
confidence: 89%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
show abstract
“…According to our analysis, H014 interactions with conserved positions F377, C379, and S383 located away from the RBM region could be important for binding and modulation of the enhanced cross-neutralization activities. These results are also in accordance with the recent structure–functional investigation of the SARS-CoV-2 S complex with H014 and P17 forming a two-antibody cocktail with synergistic neutralization achieved by simultaneously binding to distinct RBD epitopes, where H014 strongly binds to a highly conserved patch across SARS-CoV and SARS-CoV-2, while P17 targets a SARS-CoV-2-specific patch . According to this illuminating experimental study, H014 binding to conserved hotspots F377, C379, Y380, S383, and P384 is critical to promote synergistic neutralization together with the P17 antibody by acting as a shield of the S1 region and blocking the SARS-CoV-2-RBD interactions with host cellular receptors.…”
Section: Resultssupporting
confidence: 89%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
show abstract
“…S2B). Compared to recombinant S-P17-Fab structures exhibiting one-RBD-up or two-RBD-up conformations 30 , our on-virion S-P17-Fab Solo complexes on SARS-CoV-2 live -P17-Fab displayed different conformational distributions and significantly lower P17-Fab binding efficiency. Notably, a construct of prefusion-stabilized ectodomain S that exclusively adopts a one-RBD-up conformation 33 were used for recombinant studies.…”
Section: Resultsmentioning
confidence: 80%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
show abstract
“…Although S2 antigen has not been used as a vaccine, we believe that S2 could be used as a vaccine complement or detection target. We could also use the S2specific antibody in the recently proposed antibody cocktail therapy to limit the escape of viral mutants (21,30). Surprisingly that IgM positivity appeared later than IgG positivity, and the level was relatively low, which was not consistent with our understanding of the antibody response.…”
Section: Discussionmentioning
confidence: 87%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
show abstract
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