Early transmissibility assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020

Leung, Kathy; Shum, Marcus Ho-Hin; Leung, Gabriel M.; Lam, Tommy T. Y.; Wu, Joseph T.

doi:10.2807/1560-7917.es.2020.26.1.2002106

Cited by 672 publications

(644 citation statements)

References 11 publications

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“…The new SARS-CoV-2 variant B.1.1.7 is widespread in the United Kingdom (UK) and is spreading globally 37,38 . Moreover, the B.1.1.7 variant has been suggested to have higher infectivity and has mutations in the receptor binding domain that may limit neutralization efficacy of RBD-specific antibodies 37,38 . Therefore, we tested the serum from the RBD-scNP-vaccinated macaques against a pseudovirus with B.1.1.7 spike.…”

Section: Mainmentioning

confidence: 99%

SARS-CoV-2 vaccination induces neutralizing antibodies against pandemic and pre-emergent SARS-related coronaviruses in monkeys

Saunders

Lee

Parks

et al. 2021

Preprint

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Betacoronaviruses (betaCoVs) caused the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, and now the SARS-CoV-2 pandemic. Vaccines that elicit protective immune responses against SARS-CoV-2 and betaCoVs circulating in animals have the potential to prevent future betaCoV pandemics. Here, we show that immunization of macaques with a multimeric SARS-CoV-2 receptor binding domain (RBD) nanoparticle adjuvanted with 3M-052-Alum elicited cross-neutralizing antibody responses against SARS-CoV-1, SARS-CoV-2, batCoVs and the UK B.1.1.7 SARS-CoV-2 mutant virus. Nanoparticle vaccination resulted in a SARS-CoV-2 reciprocal geometric mean neutralization titer of 47,216, and robust protection against SARS-CoV-2 in macaque upper and lower respiratory tracts. Importantly, nucleoside-modified mRNA encoding a stabilized transmembrane spike or monomeric RBD protein also induced SARS-CoV-1 and batCoV cross-neutralizing antibodies, albeit at lower titers. These results demonstrate current mRNA vaccines may provide some protection from future zoonotic betaCoV outbreaks, and provide a platform for further development of pan-betaCoV nanoparticle vaccines.

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Section: Mainmentioning

confidence: 99%

SARS-CoV-2 vaccination induces neutralizing antibodies against pandemic and pre-emergent SARS-related coronaviruses in monkeys

Saunders

Lee

Parks

et al. 2021

Preprint

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“…Recently, viral variants with increased transmissibility and potential antigenic mutations have been reported in clinical isolates [34][35][36][37] . We tested whether some of the variant residues in these rapidly emerging strains would abrogate the activity of these potently neutralizing antibodies.…”

mentioning

confidence: 99%

Genetic and structural basis for recognition of SARS-CoV-2 spike protein by a two-antibody cocktail

Dong

Zost

Greaney

et al. 2021

Preprint

100

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The SARS-CoV-2 pandemic has led to an urgent need to understand the molecular basis for immune recognition of SARS-CoV-2 spike (S) glycoprotein antigenic sites. To define the genetic and structural basis for SARS-CoV-2 neutralization, we determined the structures of two human monoclonal antibodies COV2-2196 and COV2-21301, which form the basis of the investigational antibody cocktail AZD7442, in complex with the receptor binding domain (RBD) of SARS-CoV-2. COV2-2196 forms an “aromatic cage” at the heavy/light chain interface using germline-encoded residues in complementarity determining regions (CDRs) 2 and 3 of the heavy chain and CDRs 1 and 3 of the light chain. These structural features explain why highly similar antibodies (public clonotypes) have been isolated from multiple individuals1–4. The structure of COV2-2130 reveals that an unusually long LCDR1 and HCDR3 make interactions with the opposite face of the RBD from that of COV2-2196. Using deep mutational scanning and neutralization escape selection experiments, we comprehensively mapped the critical residues of both antibodies and identified positions of concern for possible viral escape. Nonetheless, both COV2-2196 and COV2130 showed strong neutralizing activity against SARS-CoV-2 strain with recent variations of concern including E484K, N501Y, and D614G substitutions. These studies reveal germline-encoded antibody features enabling recognition of the RBD and demonstrate the activity of a cocktail like AZD7442 in preventing escape from emerging variant viruses.

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“…The United Kingdom variant, known as 20I/501Y.V1 (synonyms: VOC 202012/01, or B.1.1.7), emerged around September 2020 with an atypically large number of mutations, particularly within RBD including N501Y, P681H proximal to the furin cleavage site S1/S2; position 69/70 deletion resulting in a conformation change in the spike, and ORF8 stop codon insertion, Q27 with an unknown function [163]. Similar to what has been previously seen in SARS-CoV-1, a deleterious 29 nucleotide deletion was found in ORF8, which plays a role in immune evasion and interferon suppression of SARS-CoV-2 and is considered one of the least conserved proteins among coronaviruses [164,165].…”

Section: United Kingdom Variant B117mentioning

confidence: 99%

SARS–CoV-2 Immuno-Pathogenesis and Potential for Diverse Vaccines and Therapies: Opportunities and Challenges

McGill

Kahlil

Dutta

et al. 2021

Infectious Disease Reports

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Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a novel coronavirus that emerged from Wuhan, China in late 2019 causing coronavirus disease-19 (COVID-19). SARS-CoV-2 infection begins by attaching to angiotensin-converting enzyme 2 receptor (ACE2) via the spike glycoprotein, followed by cleavage by TMPRSS2, revealing the viral fusion domain. Other presumptive receptors for SARS-CoV-2 attachment include CD147, neuropilin-1 (NRP1), and Myeloid C-lectin like receptor (CLR), each of which might play a role in the systemic viral spread. The pathology of SARS-CoV-2 infection ranges from asymptomatic to severe acute respiratory distress syndrome, often displaying a cytokine storm syndrome, which can be life-threatening. Despite progress made, the detailed mechanisms underlying SARS-CoV-2 interaction with the host immune system remain unclear and are an area of very active research. The process’s key players include viral non-structural proteins and open reading frame products, which have been implicated in immune antagonism. The dysregulation of the innate immune system results in reduced adaptive immune responses characterized by rapidly diminishing antibody titers. Several treatment options for COVID-19 are emerging, with immunotherapies, peptide therapies, and nucleic acid vaccines showing promise. This review discusses the advances in the immunopathology of SARS-CoV-2, vaccines and therapies under investigation to counter the effects of this virus, as well as viral variants.

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Early transmissibility assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020

Cited by 672 publications

References 11 publications

SARS-CoV-2 vaccination induces neutralizing antibodies against pandemic and pre-emergent SARS-related coronaviruses in monkeys

SARS-CoV-2 vaccination induces neutralizing antibodies against pandemic and pre-emergent SARS-related coronaviruses in monkeys

Genetic and structural basis for recognition of SARS-CoV-2 spike protein by a two-antibody cocktail

SARS–CoV-2 Immuno-Pathogenesis and Potential for Diverse Vaccines and Therapies: Opportunities and Challenges

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