The effect of SARS-CoV-2 D614G mutation on BNT162b2 vaccine-elicited neutralization

Zou, Jing; Xie, Xuping; Fontes-Garfias, Camila R.; Swanson, Kena A.; Kanevsky, Isis; Tompkins, Kristin; Cutler, Mark; Cooper, David A.; Dormitzer, Philip R.; Shi, Pei–Yong

doi:10.1038/s41541-021-00313-8

Cited by 40 publications

(29 citation statements)

References 17 publications

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“…Our studies of in vitro neutralization of a variety of SARS-CoV-2 variants have, to date, found that all tested BNT162b2-immune sera neutralize all tested variants. 13,[27][28][29][30][31] The variant with the greatest reduction in neutralization, B.1.351, which has been the dominant South African strain, is still neutralized at serum titers higher than those observed at the onset of protection against COVID-19 after the first vaccine dose. 9,13,19 Consistent with this finding, BNT162b2 had 100% (95% CI 53.5, 100.0) observed efficacy against COVID-19 in South Africa (placebo recipients, 9 cases; BNT162b2 recipients, 0 cases), and 8/9 cases for which sequence information could be obtained were B.1.351 lineage SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 99%

Six Month Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine

Thomas

Moreira

Kitchin

et al. 2021

Preprint

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118

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Background: BNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine encoding a prefusion-stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. BNT162b2 is highly efficacious against COVID-19 and is currently authorized for emergency use or conditional approval worldwide. At the time of authorization, data beyond 2 months post-vaccination were unavailable. Methods: In an ongoing, placebo-controlled, observer-blinded, multinational, pivotal efficacy study, 44,165 ≥16-year-old participants and 2,264 12-15-year-old participants were randomized to receive 2 doses, 21 days apart, of 30 μg BNT162b2 or placebo. Study endpoints reported here are vaccine efficacy (VE) against laboratory-confirmed COVID-19 and safety data, both up to 6 months post-vaccination. Results: BNT162b2 continued to be safe and well tolerated. Few participants had adverse events leading to study withdrawal. VE against COVID-19 was 91% (95% CI 89.0‒93.2) through up to 6 months of follow-up, among evaluable participants and irrespective of previous SARS-CoV-2 infection. VE of 86%‒100% was seen across countries and in populations with diverse characteristics of age, sex, race/ethnicity, and COVID-19 risk factors in participants without evidence of previous SARS-CoV-2 infection. VE against severe disease was 97% % (95% CI 80.3‒99.9). In South Africa, where the SARS-CoV-2 variant of concern, B.1.351 (beta), was predominant, 100% (95% CI 53.5, 100.0) VE was observed. Conclusion: With up to 6 months of follow-up and despite a gradually declining trend in vaccine efficacy, BNT162b2 had a favorable safety profile and was highly efficacious in preventing COVID-19. (ClinicalTrials.gov number, NCT04368728)

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Section: Discussionmentioning

confidence: 99%

Six Month Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine

Thomas

Moreira

Kitchin

et al. 2021

Preprint

Self Cite

118

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“…D614G may also be responsible for increasing the number of spike proteins per virion 141,142 and the rate of S1/S2 cleavage 143 . Viruses with D614G have been slightly more susceptible to neutralization by mAbs, convalescent plasma and plasma from vaccinated individuals in some studies 138,144 and slightly more resistant to neutralization in other studies 136,145 .…”

Section: D614gmentioning

confidence: 99%

The biological and clinical significance of emerging SARS-CoV-2 variants

et al. 2021

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Among the many unprecedented aspects of the SARS-CoV-2 pandemic is the intense virological monitoring that has occurred, with more than two million virus isolates having undergone partial or complete genomic sequencing. Initially, genetic sequencing suggested that SARS-CoV-2 was exceptionally well adapted to humans, spreading rapidly with little evidence for natural selection among circulating viruses. This changed during the later months of 2020, with the first reports of emergent SARS-CoV-2 variants associated with increased transmissibility, disease severity and escape from humoral immunity.In this Review, we create a framework for understanding SARS-COV-2 variants by describing fundamental aspects of SARS-CoV-2 evolution, the structure and function of the SARS-CoV-2 spike protein and the laboratory methods used to characterize spike variants. We then describe the biological properties and epidemiological characteristics of these variants and their associated mutations. Lastly, we describe the types of study required for the research, clinical and public health communities to respond to the new threat posed by emerging SARS-CoV-2 variants. Given the wide public interest in this topic, we provide a box of key points. We also provide a repository of the SARS-CoV-2 variant neutralization data discussed in this Review (Stanford University Coronavirus Antiviral & Resistance Database -Susceptibility Data). SARS-CoV-2 evolutionCoronaviruses contain an exonuclease enzyme that reduces their replication error rate by about 15-fold to 20-fold in vitro, resulting in an in vivo viral mutation rate about 10-fold lower than that of influenza 1-3 . Nonetheless, they accumulate mutations and generate further diversity through the process of recombination when variants with different mutations infect the same host [4][5][6] . Recombination between different SARS-related coronaviruses is likely to have led to the emergence of SARS-CoV-2 (ref. 7 ) and, although it can be difficult to detect owing to the similarity of most sequences, recombination is occurring to some extent among circulating SARS-CoV-2 variants 6,8 . Additionally, host-mediated RNA editing by APOBeC and ADAr enzymes, as evidenced by the dominance of C to U changes in specific dinucleotide contexts, contributes to SARS-CoV-2 diversity 9,10 .Although it had been previously assumed that waning immunity explained the observation that people are commonly reinfected with endemic common-cold coronaviruses 11 , recent studies suggest that antigenic drift also contributes to the lack of long-lasting protection following coronavirus infections 12,13 . HCoV-229E and HCoV-OC43 sequences over a 30-year period demonstrate a ladder-like phylogenetic tree topology consistent with the emergence of novel variants sweeping

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“…2). Except lineage A, all isolates (lineages B, P, and R) have the S gene D614G mutation located in the receptor-binding motif, which has been reported to have a modest impact on vaccine-elicited neutralization 21 . For each isolate we highlight key S protein amino acid differences in the antigenic regions of the amino-terminal domain (NTD), RBD-ACE2 interface, and furin cleavage site (FCS) (Figure 3a).…”

Section: Vaccine-induced Nab Against Variantsmentioning

confidence: 99%

Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity

Lucas

Vogels

Yıldırım

et al. 2021

Nature

198

159

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This is a PDF file of a peer-reviewed paper that has been accepted for publication. Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and figures will undergo copyediting and a proof review before the paper is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

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The effect of SARS-CoV-2 D614G mutation on BNT162b2 vaccine-elicited neutralization

Cited by 40 publications

References 17 publications

Six Month Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine

Six Month Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine

The biological and clinical significance of emerging SARS-CoV-2 variants

Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity

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