Immunodominant antibody germlines in COVID-19

Andreano, Emanuele; Rappuoli, Rino

doi:10.1084/jem.20210281

Cited by 30 publications

(30 citation statements)

References 15 publications

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“…The hCoV-2IG antibodies most frequently bound to sites in the NTD, S1/S2 cleavage site, fusion peptide and heptad repeat domains in S2. In recent studies with monoclonal antibodies isolated from SARS-CoV-2 memory cells from COVID-19 patients, multiple neutralizing antibodies were identified that targeted the RBD, S1-NTD, S2, and S protein trimer (Andreano and Rappuoli, 2021;Fagiani et al, 2020;Wrapp et al, 2020). The most potent neutralizing antibodies that target directly the RBM/ACE2 interface were isolated at low frequency (Andreano et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Epitope diversity of SARS-CoV-2 hyperimmune intravenous human immunoglobulins and neutralization of variants of concern

Tang¹,

Lee²,

Ravichandran³

et al. 2021

iScience

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Hyperimmune immunoglobulin (hCoV-2IG) generated from SARS-CoV-2 convalescent plasma (CP) are under evaluation in clinical trials. Here we explored the antibody epitope repertoire, and virus neutralizing capacity of six hCoV-2IG batches as well as nine CP against SARS-CoV-2 and emerging variants of concern (VOCs). Epitope-mapping by gene-fragment phage display library spanning the SARS-CoV-2 spike demonstrated broad recognition of multiple antigenic sites spanning the entire spike that was higher for hCoV-2IG than CP, with predominant binding to the fusion peptide. In the pseudovirus neutralization assay and in the wild-type SARS-CoV-2 PRNT assay, hCoV-2IG lots showed higher titers against the WA-1 strain compared with CP. Neutralization of VOCs were reduced to different extent by hCoV-2IG lots but were higher than CP. Significant reduction of hCoV-2IG binding was observed to RBD-E484K followed by RBD-N501Y (but not RBD-K417N). This study suggests that post-exposure treatment with hCoV-2IG could be preferable to CP.

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Section: Discussionmentioning

confidence: 99%

Epitope diversity of SARS-CoV-2 hyperimmune intravenous human immunoglobulins and neutralization of variants of concern

Tang¹,

Lee²,

Ravichandran³

et al. 2021

iScience

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show abstract

“…The resulting data set presented here is comprised of a representative subset of a diverse panel of candidate antibodies spanning multiple epitopes with high affinity and both receptor blocking and non-blocking activity. Interestingly, all candidate antibodies identified from the Alloy mice fell within a similar non-blocking bin, likely indicative of epitope immunodominance [ 17 ], which has been reported as a common result from COVID-19 infection [ 18 , 19 ]. However, the extended immunization strategy employed for the Alloy mice resulted in high-affinity antibodies, including the top four highest affinity candidates presented here.…”

Section: Discussionmentioning

confidence: 98%

Accelerated antibody discovery targeting the SARS-CoV-2 spike protein for COVID-19 therapeutic potential

Mullen¹,

Abdullah²,

Boucher³

et al. 2021

Antibody Therapeutics

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Background: Rapid deployment of technologies capable of high-throughput and high-resolution screening is imperative for timely response to viral outbreaks. Risk mitigation in the form of leveraging multiple advanced technologies further increases the likelihood of identifying efficacious treatments in an aggressive timeline. Methods: In this study, we describe two parallel, yet distinct, in vivo approaches for accelerated discovery of antibodies targeting the SARS-CoV-2 spike protein. Working with human transgenic Alloy-GK mice, we detail a single B-cell discovery workflow to directly interrogate antibodies secreted from plasma cells for binding specificity and ACE2 receptor blocking activity. Additionally, we describe a concurrent accelerated hybridoma-based workflow utilizing a DiversimAb™ mouse model for increased diversity. Results: The panel of antibodies isolated from both workflows revealed binding to distinct epitopes with both blocking and non-blocking profiles. Sequence analysis of the resulting lead candidates uncovered additional diversity with the opportunity for straightforward engineering and affinity maturation. Conclusions: By combining in vivo models with advanced integration of screening and selection platforms, lead antibody candidates can be sequenced and fully characterized within one to three months.

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“…Interestingly, all candidate antibodies identified from the Alloy mice fell within a similar nonblocking bin, likely indicative of epitope immunodominance, 14 which has been reported as a common result from COVID-19 infection. 15,16 However, the extended immunization strategy employed for the Alloy mice resulted in high affinity antibodies, including the top four highest affinity candidates presented here. The balance between diversity and affinity is a challenge for in vivo immunization models:…”

mentioning

confidence: 89%

Accelerated Antibody Discovery Targeting the SARS-CoV-2 Spike Protein for COVID-19 Therapeutic Potential

Mullen

Abdullah

Boucher

et al. 2021

Preprint

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Rapid deployment of technologies capable of high-throughput and high-resolution screening is imperative for timely response to viral outbreaks. Risk mitigation in the form of leveraging multiple advanced technologies further increases the likelihood of identifying efficacious treatments in an aggressive timeline. In this study, we describe two parallel, yet distinct, in vivo approaches for accelerated discovery of antibodies targeting the SARS-CoV-2 spike protein. Working with human transgenic Alloy-GK mice, we detail a single B-cell discovery workflow to directly interrogate antibodies secreted from plasma cells for binding specificity and ACE2 receptor blocking activity. Additionally, we describe a concurrent accelerated hybridoma-based workflow utilizing a DiversimAb mouse model for increased diversity. The panel of antibodies isolated from both workflows revealed binding to distinct epitopes with both blocking and non-blocking profiles. Sequence analysis of the resulting lead candidates uncovered additional diversity with the opportunity for straightforward engineering and affinity maturation. By combining in vivo models with advanced integration of screening and selection platforms, lead antibody candidates can be sequenced and fully characterized within one to three months.

show abstract

Immunodominant antibody germlines in COVID-19

Cited by 30 publications

References 15 publications

Epitope diversity of SARS-CoV-2 hyperimmune intravenous human immunoglobulins and neutralization of variants of concern

Epitope diversity of SARS-CoV-2 hyperimmune intravenous human immunoglobulins and neutralization of variants of concern

Accelerated antibody discovery targeting the SARS-CoV-2 spike protein for COVID-19 therapeutic potential

Accelerated Antibody Discovery Targeting the SARS-CoV-2 Spike Protein for COVID-19 Therapeutic Potential

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