Neutralizing Antibody and Soluble ACE2 Inhibition of a Replication-Competent VSV-SARS-CoV-2 and a Clinical Isolate of SARS-CoV-2

Case, James Brett; Rothlauf, Paul W.; Chen, Rita E.; Liu, Zhuoming; Zhao, Haiyan; Kim, Arthur S.; Bloyet, Louis-Marie; Zeng, Qiru; Tahan, Stephen; Droit, Lindsay; Ilagan, Ma. Xenia G.; Tartell, Michael A.; Amarasinghe, Gaya K.; Henderson, Jeffrey P.; Miersch, Shane; Ustav, Mart; Sidhu, Sachdev S.; Virgin, Herbert W.; Wang, David; Ding, Siyuan; Corti, Davide; Theel, Elitza S.; Fremont, Daved H.; Diamond, Michael S.; Whelan, Sean P. J.

doi:10.1016/j.chom.2020.06.021

Cited by 401 publications

(466 citation statements)

References 64 publications

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“…Whereas ChAd-SARS-CoV-2-S induced high levels of S-and RBD-specific IgG, low, if any levels were detected in the ChAd-controlimmunized mice (Fig 1D and S1A). Serum samples were assayed in vitro for neutralization of infectious SARS-CoV-2 using a focus-reduction neutralization test (FRNT) (Case et al, 2020). As expected, serum from ChAd-control-immunized mice did not inhibit SARS-CoV-2 infection after primary immunization or boosting.…”

Section: Resultsmentioning

confidence: 71%

A single intranasal dose of chimpanzee adenovirus-vectored vaccine confers sterilizing immunity against SARS-CoV-2 infection

Hassan

Kafai

Dmitriev

et al. 2020

Preprint

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SUMMARYThe Coronavirus Disease 2019 pandemic has made deployment of an effective vaccine a global health priority. We evaluated the protective activity of a chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike protein (ChAd-SARS-CoV-2-S) in challenge studies with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mice expressing the human angiotensin-converting enzyme 2 receptor. Intramuscular dosing of ChAd-SARS-CoV-2-S induces robust systemic humoral and cell-mediated immune responses and protects against lung infection, inflammation, and pathology but does not confer sterilizing immunity, as evidenced by detection of viral RNA and induction of anti-nucleoprotein antibodies after SARS-CoV-2 challenge. In contrast, a single intranasal dose of ChAd-SARS-CoV-2-S induces high levels of systemic and mucosal IgA and T cell responses, completely prevents SARS-CoV-2 infection in the upper and lower respiratory tracts, and likely confers sterilizing immunity in most animals. Intranasal administration of ChAd-SARS-CoV-2-S is a candidate for preventing SARS-CoV-2 infection and transmission, and curtailing pandemic spread.

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Section: Resultsmentioning

confidence: 71%

A single intranasal dose of chimpanzee adenovirus-vectored vaccine confers sterilizing immunity against SARS-CoV-2 infection

Hassan

Kafai

Dmitriev

et al. 2020

Preprint

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“…We next examined if the escape maps accurately predicted the mutants selected when virus is grown in the presence of antibody. To investigate this, we used a recombinant replication-competent vesicular stomatitis virus (VSV) expressing the SARS-CoV-2 spike in place of the endogenous VSV glycoprotein (G) (Case et al, 2020) . Such viruses provide a facile system to select for spike mutations that evade antibody neutralization (Case et al, 2020;Dieterle et al, 2020;Weisblum et al, 2020) .…”

Section: Escape Maps Predict Results Of Antibody Selection Experimentsmentioning

confidence: 99%

“…The generation of a replication-competent vesicular stomatitis virus (VSV) expressing SARS-CoV-2 S protein that replaces VSV G protein (VSV-SARS-CoV-2) has been described previously (Case et al, 2020) . This virus encodes the spike protein from SARS-CoV-2 with a 21 amino-acid C-terminal deletion.…”

Section: Vsv Viruses Expressing Sars-cov-2 Spike Proteinmentioning

confidence: 99%

Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition

Greaney

Starr

Gilchuk

et al. 2020

Preprint

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Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and make a major contribution to the neutralizing antibody response elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding, and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same RBD surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies, and enable us to design escape-resistant antibody cocktails–including cocktails of antibodies that compete for binding to the same surface of the RBD but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution.

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“…A number of surrogate assays that aim to identify molecules with activity against proteins encoded by SARS-CoV-2 have recently been reported [37][38][39] . These assays were developed to provide (Table 1).…”

Section: Discussionmentioning

confidence: 99%

A simplified cell-based assay to identify coronavirus 3CL protease inhibitors

Resnick

Iketani

Hong

et al. 2020

Preprint

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We describe a mammalian cell-based assay capable of identifying coronavirus 3CL protease (3CLpro) inhibitors without requiring the use of live virus. By enabling the facile testing of compounds across a range of coronavirus 3CLpro enzymes, including the one from SARS-CoV-2, we are able to quickly identify compounds with broad or narrow spectra of activity. We further demonstrate the utility of our approach by performing a curated compound screen along with structure-activity profiling of a series of small molecules to identify compounds with antiviral activity. Throughout these studies, we observed concordance between data emerging from this assay and from live virus assays. By democratizing the testing of 3CL inhibitors to enable screening in the majority of laboratories rather than the few with extensive biosafety infrastructure, we hope to expedite the search for coronavirus 3CL protease inhibitors, to address the current epidemic and future ones that will inevitably arise.

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Neutralizing Antibody and Soluble ACE2 Inhibition of a Replication-Competent VSV-SARS-CoV-2 and a Clinical Isolate of SARS-CoV-2

Cited by 401 publications

References 64 publications

A single intranasal dose of chimpanzee adenovirus-vectored vaccine confers sterilizing immunity against SARS-CoV-2 infection

A single intranasal dose of chimpanzee adenovirus-vectored vaccine confers sterilizing immunity against SARS-CoV-2 infection

Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition

A simplified cell-based assay to identify coronavirus 3CL protease inhibitors

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