Increased transmission of SARS-CoV-2 lineage B.1.1.7 (VOC 2020212/01) is not accounted for by a replicative advantage in primary airway cells or antibody escape

Abstract

Lineage B.1.1.7 (Variant of Concern 202012/01) is a new SARS-CoV-2 variant which was first sequenced in the UK in September 2020 before becoming the majority strain in the UK and spreading worldwide. The rapid spread of the B.1.1.7 variant results from increased transmissibility but the virological characteristics which underpin this advantage over other circulating strains remain unknown. Here, we demonstrate that there is no difference in viral replication between B.1.1.7 and other contemporaneous SARS-CoV-2 strains in primary human airway epithelial (HAE) cells. However, B.1.1.7 replication is disadvantaged in Vero cells potentially due to increased furin-mediated cleavage of its spike protein as a result of a P681H mutation directly adjacent to the S1/S2 cleavage site. In addition, we show that B.1.1.7 does not escape neutralisation by convalescent or post-vaccination sera. Thus, increased transmission of B.1.1.7 is not caused by increased replication, as measured on HAE cells, or escape from serological immunity.

The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape

“…V1 infections have been associated with increased viral loads at the nasopharynx 32 which suggests that increased transmissibility may simply be a consequence of increased numbers of viral particles per exhaled infectious droplet. There is, however, conflicting data on this point with some indications that V1 infections might not in fact be associated with higher viral loads 59,60 . Currently there is no available data on how well the V1, V2 and V3 lineage viruses survive in the environment relative to those of other SARS-CoV-2 lineages.…”

Direct RT-qPCR assay for SARS-CoV-2 variants of concern (Alpha, B.1.1.7 and Beta, B.1.351) detection and quantification in wastewater

“…This may imply different gene expression distributions or different durability of the RNA segments in the wastewater ( Emanuel et al, 2021 ; Kim et al, 2020 ). As it is known that the Alpha variant has a more potent expression than the original NC_045512.2 ( Brown et al, 2021 ; Parker et al, 2021 ), the fact that positive SΔ69 detection is closer to the N gene detection than the proximity of positive S1 detection compared to N gene detection is understandable. However, these observations need further study and validation.…”

Evolution of enhanced innate immune evasion by the SARS-CoV-2 B.1.1.7 UK variant

“…SARS-CoV-2 isolate VIC was provided by NISBC, and IC19, B.1.1.7, B.1.1.7 (B) and B.1.1.7 (C) are reported in 11 , full isolate names and GISAID references are listed below. Viruses were propagated by infecting Caco-2 cells at MOI 0.01 TCID50/cell, in culture medium at 37°C.…”

“…Calu-3 cells were grown to 60-80% confluence prior to infection as described previously 23 . 11 , full isolate names and GISAID references are listed below. Viruses were propagated by infecting Caco-2 cells at MOI 0.01 TCID50/cell, in culture medium at 37°C.…”

“…This has led the field to focus on understanding viral escape from wave one (early-lineage) driven adaptive immunity and its implications for infection control and vaccine development. Fortunately, despite adaptation of Spike, B.1.1.7 remains sensitive to vaccine- and infection-induced neutralising antibodies 9–11 . B.1.1.7 variant of concern (VOC)-defining mutations outside Spike suggest that Spike-independent adaptation to host may contribute to the B.1.1.7 transmission advantage.…”