Neutralizing Activity of BNT162b2-Elicited Serum

Liu, Yang; Liu, Jianying; Xia, Hongjie; Zhang, Xianwen; Fontes-Garfias, Camila R.; Swanson, Kena A.; Cai, Hui; Sarkar, Ritu; Chen, Wei; Cutler, Mark; Cooper, David A.; Weaver, Scott C.; Muik, Alexander; Şahin, Uğur; Jansen, Kathrin U.; Xie, Xuping; Dormitzer, Philip R.; Shi, Pei Yong

doi:10.1056/nejmc2102017

Cited by 578 publications

(526 citation statements)

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“…Whereas we did find these substitutions in swabs obtained 1 DPI, they were not present in swabs obtained at 5 DPI. Likewise, the substitutions were only found in lung tissue of one out of four control hamsters ( conclude that the substitutions found in the B.1.1.7 spike protein have limited to no effect on virus neutralization titres [9][10][11][12][13][14][15] . Data from a UK phase III trial taken from a time when B.1.1.7 predominated, showed minimal impact on ChAdOx1 nCoV-19 vaccine efficacy .…”

Section: Substitution (Wuhanmentioning

confidence: 85%

“…Likewise, in an observational study of vaccine effectiveness in adults aged over 70 years in the UK, a single dose of either ChAdOx1 nCoV-19 or the Pfizer/BioNTech vaccine BNT162b2 reduced hospitalization in elderly adults with co-morbidities by 80% 16 . In contrast, the substitutions found in the B.1.351 spike protein (Table 1) result in a significant reduction of virus neutralizing capacity with pseudotype or infectious virus neutralization assays [9][10][11][12][13][14][15]17,18 . In a phase II study of It should be noted that the B.1.351 virus stock used to challenge hamsters contained two additional non-fixed AA substitutions; Q677H and R682W at 88% and 89%, respectively.…”

Section: Substitution (Wuhanmentioning

confidence: 95%

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ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7

Fischer

Doremalen

Adney

et al. 2021

Preprint

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We investigated ChAdOx1 nCoV-19 (AZD1222) vaccine efficacy against SARS-CoV-2 variants of concern (VOCs) B.1.1.7 and B.1.351 in Syrian hamsters. We previously showed protection against SARS-CoV-2 disease and pneumonia in hamsters vaccinated with a single dose of ChAdOx1 nCoV-19. Here, we observed a 9.5-fold reduction of virus neutralizing antibody titer in vaccinated hamster sera against B.1.351 compared to B.1.1.7. Vaccinated hamsters challenged with B.1.1.7 or B.1.351 did not lose weight compared to control animals. In contrast to control animals, the lungs of vaccinated animals did not show any gross lesions. Minimal to no viral subgenomic RNA (sgRNA) and no infectious virus was detected in lungs of vaccinated animals. Histopathological evaluation showed extensive pulmonary pathology caused by B.1.1.7 or B.1.351 replication in the control animals, but none in the vaccinated animals. These data demonstrate the effectiveness of the ChAdOx1 nCoV-19 vaccine against clinical disease caused by B.1.1.7 or B.1.351 VOCs.

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Section: Substitution (Wuhanmentioning

confidence: 85%

Section: Substitution (Wuhanmentioning

confidence: 95%

ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7

Fischer

Doremalen

Adney

et al. 2021

Preprint

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“…However, the Oxford-AstraZeneca vaccine has displayed compromised efficacy against the B.1.351 variant with 21.4% (35). Preliminary data with the Pfizer-BioNTech and Moderna mRNA vaccines also show reduction of efficacy against B.1.351 (34,36). Furthermore, there is likely epistatic mutations in the S protein.…”

Section: Discussionmentioning

confidence: 98%

Meta-Analysis and Structural Dynamics of the Emergence of Genetic Variants of SARS-CoV-2

Castonguay

Zhang

Langlois

2021

Preprint

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The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerged in late December 2019 in Wuhan, China, and is the causative agent for the worldwide COVID-19 pandemic. SARS-CoV-2 is a 29,811 nucleotides positive-sense single-stranded RNA virus belonging to the betacoronavirus genus. Due to inefficient proofreading ability of the viral RNA-dependent polymerase complex, coronaviruses are known to acquire new mutations following replication, which constitutes one of the main factors driving the evolution of its genome and the emergence of new genetic variants. In the last few months, the identification of new B.1.1.7 (UK), B.1.351 (South Africa) and P.1 (Brazil) variants of concern (VOC) highlighted the importance of tracking the emergence of mutations in the SARS-CoV-2 genome and their impact on transmissibility, infectivity, and neutralizing antibody escape capabilities. These VOC demonstrate increased transmissibility and antibody escape, and reduce current vaccine efficacy. Here we analyzed the appearance and prevalence trajectory of mutations that appeared in all SARS-CoV-2 genes from December 2019 to January 2021. Our goals were to identify which modifications are the most frequent, study the dynamics of their spread, their incorporation into the consensus sequence, and their impact on virus biology. We also analyzed the structural properties of the spike glycoprotein of the B.1.1.7, B.1.351 and P.1 variants. This study offers an integrative view of the emergence, disappearance, and consensus sequence integration of successful mutations that constitute new SARS-CoV-2 variants and their impact on neutralizing antibody therapeutics and vaccines.

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“…Such results may impact the congruity of data across laboratories and interpretation of effects of viral variants on vaccine efficacy. As an example, recent studies with Vero E6 cell-derived SARS-CoV-2 with spike proteins containing some (E484K, N501Y and D614G) or all of the South African mutations showed smaller 1.2 to 2.7-fold decreases in neutralization potency by BNT162b2 mRNA vaccine-elicited human immune sera 22,45 . When we compared neutralization of deep-sequenced confirmed p0 (Vero E6 cell-produced) and p1 (Vero-hACE2-TMPRSS2 cell-produced) K417N/E484K/N501Y/ D614G viruses by immune serum from vaccinated animals or humans or naturally infected humans in the same recipient Vero-hACE2-TMPRSS2 cells, the viruses produced in Vero E6 cells were neutralized more efficiently (two-to threefold, P < 0.05) than those propagated in Vero-hACE2-TMPRSS2 cells (Extended Data Fig.…”

Section: Discussionmentioning

confidence: 99%

Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies

Chen

Zhang

Case

et al. 2021

Nat Med

Self Cite

919

962

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evere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic infecting more than 111 million people and causing 2.4 million deaths. Clinical disease in humans ranges from asymptomatic infection to pneumonia, severe respiratory compromise, multi-organ failure and systemic inflammatory syndromes. The rapid expansion and prolonged nature of the COVID-19 pandemic and its accompanying morbidity, mortality and destabilizing socioeconomic effects have made the development of SARS-CoV-2 therapeutics and vaccines an urgent global health priority 1. Indeed, the emergency use authorization and rapid deployment of antibody-based countermeasures, including mAbs, immune plasma therapy and messenger RNA, and inactivated and viral-vectored vaccines has provided hope for curtailing disease and ending the pandemic. The spike protein of the SARS-CoV-2 virion binds the cell-surface receptor angiotensin-converting enzyme 2 (ACE2) to promote entry into human cells 2. Because the spike protein is critical for viral entry, it has been targeted for vaccine development and therapeutic antibody interventions. SARS-CoV-2 S proteins are cleaved to yield S1 and S2 fragments. The S1 protein includes the N-terminal (NTD) and receptor-binding (RBD) domains, whereas the S2 protein promotes membrane fusion. The RBD is recognized by many potently neutralizing monoclonal antibodies 3-7 , protein-based inhibitors 8 and serum antibodies 9. The current suite of antibody therapeutics and vaccines was designed with a spike protein based on strains circulating during the early phases of the pandemic in 2020. More recently, variants with enhanced transmissibility have emerged in the United Kingdom (B.1.1.7), South Africa (B.1.351), Brazil (B.1.1.248) and elsewhere with multiple substitutions in the spike protein, including in the NTD and the receptor-binding motif (RBM) of the RBD. Preliminary studies with pseudoviruses suggest that neutralization by some antibodies and immune sera may be diminished against variants expressing mutations in the spike gene 10-13. Given these

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Neutralizing Activity of BNT162b2-Elicited Serum

Cited by 578 publications

References 4 publications

ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7

ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7

Meta-Analysis and Structural Dynamics of the Emergence of Genetic Variants of SARS-CoV-2

Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies

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