Alpha (B.1.1.7) and Delta (B.1.617.2 – AY.40) SARS-CoV-2 variants present strong neutralization decay at M4 post-vaccination and a faster replication rates than D614G (B.1) lineage

Lebourgeois, Samuel; Menidjel, Reyene; Chenane, Houssem Redha; Ferré, Valentine Marie; Collin, Gilles; Damond, Florence; Coppée, Romain; Yazdanpanah, Yazdan; Timsit, Jean‐François; Houhou‐Fidouh, Nadhira; Descamps, Diane; Charpentier, Charlotte; Visseaux, Benoît

doi:10.1016/j.jinf.2021.11.012

Cited by 4 publications

(4 citation statements)

References 10 publications

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“…Kinetics of anti-S SARS-CoV-2 antibodies is described in Supplementary Figure 1. We report the results of live virus neutralization for Omicron and others VOCs until one month after the third vaccine dose ( Figure 1 A), extending our previous data [ 3 , 5 ]. We showed that Omicron neutralization titers were in median 16- and 8-fold lower than the Delta ones, one month after the second and one month after the third dose, respectively.…”

supporting

confidence: 87%

Vaccine Ab neutralization against Omicron and SARS-CoV-2 variants using neutralization and specific ELISA assays

Ferré

Lebourgeois

Chenane

et al. 2022

Journal of Infection

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supporting

confidence: 87%

Vaccine Ab neutralization against Omicron and SARS-CoV-2 variants using neutralization and specific ELISA assays

Ferré

Lebourgeois

Chenane

et al. 2022

Journal of Infection

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“…Over 20 clones were isolated and challenged with WT SARS-CoV-2, with most clones showing >60% infectivity. To test its susceptibility to different SARS-CoV-2 variants, we infected ACE2plusC3 cells with the WT virus or the delta and omicron variants and compared them with commercial A549-hACE2-TMPRSS2 cells (“IVG-AT”) used by researchers studying SARS-CoV-2 [ 13 , 14 , 15 ]. As shown in Figure 2 B, viral nucleocapsid protein (NP) was detected in most ACE2plusC3 cells 48 h post-infection.…”

Section: Resultsmentioning

confidence: 99%

A Newly Engineered A549 Cell Line Expressing ACE2 and TMPRSS2 Is Highly Permissive to SARS-CoV-2, Including the Delta and Omicron Variants

Chang

Parsi

Somasundaran

et al. 2022

Viruses

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New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, causing surges, breakthrough infections, and devastating losses—underscoring the importance of identifying SARS-CoV-2 antivirals. A simple, accessible human cell culture model permissive to SARS-CoV-2 variants is critical for identifying and assessing antivirals in a high-throughput manner. Although human alveolar A549 cells are a valuable model for studying respiratory virus infections, they lack two essential host factors for SARS-CoV-2 infection: angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). SARS-CoV-2 uses the ACE2 receptor for viral entry and TMPRSS2 to prime the SARS-CoV-2 spike protein, both of which are negligibly expressed in A549 cells. Here, we report the generation of a suitable human cell line for SARS-CoV-2 studies by transducing human ACE2 and TMPRSS2 into A549 cells. We show that subclones highly expressing ACE2 and TMPRSS2 (“ACE2plus” and the subclone “ACE2plusC3”) are susceptible to infection with SARS-CoV-2, including the delta and omicron variants. These subclones express more ACE2 and TMPRSS2 transcripts than existing commercial A549 cells engineered to express ACE2 and TMPRSS2. Additionally, the antiviral drugs EIDD-1931, remdesivir, nirmatrelvir, and nelfinavir strongly inhibit SARS-CoV-2 variants in our infection model. Our data show that ACE2plusC3 cells are highly permissive to SARS-CoV-2 infection and can be used to identify anti-SARS-CoV-2 drugs.

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“…The quantity of virus necessary to activate neutrophils seemed relatively large as compared to what is usually necessary to infect epithelial cells ( 28 ). However, at infection sites there is a huge amplification of viral particles due to viral replication.…”

Section: Discussionmentioning

confidence: 99%

Differential activation of human neutrophils by SARS-CoV-2 variants of concern

et al. 2022

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The emerging SARS-CoV-2 virus has affected the entire world with over 600 million confirmed cases and 6.5 million deaths as of September 2022. Since the beginning of the pandemic, several variants of SARS-CoV-2 have emerged, with different infectivity and virulence. Several studies suggest an important role of neutrophils in SARS-Cov-2 infection severity, but data about direct activation of neutrophils by the virus is scarce. Here, we studied the in vitro activation of human neutrophils by SARS-CoV-2 variants of concern (VOCs). In our work, we show that upon stimulation with SARS-Cov-2 infectious particles, human healthy resting neutrophils upregulate activation markers, degranulate IL-8, produce Reactive Oxygen Species and release Neutrophil Extracellular Traps. Neutrophil activation was dependent on TLR7/8 and IRF3/STING. We then compared the activation potential of neutrophils by SARS-CoV-2 variants and showed a significantly increased activation by the Delta variant and a decreased activation by the Omicron variant as compared to the initial strain. In this study, we demonstrate that the SARS-Cov-2 virus can directly activate neutrophils in COVID-19 and that the different VOCs had differences in neutrophil activation intensity that mirror the differences of clinical severity. These data highlight the need to address neutrophil-virus interactions as a potential target for therapeutic intervention in SARS-CoV-2 infection.

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Alpha (B.1.1.7) and Delta (B.1.617.2 – AY.40) SARS-CoV-2 variants present strong neutralization decay at M4 post-vaccination and a faster replication rates than D614G (B.1) lineage

Cited by 4 publications

References 10 publications

Vaccine Ab neutralization against Omicron and SARS-CoV-2 variants using neutralization and specific ELISA assays

Vaccine Ab neutralization against Omicron and SARS-CoV-2 variants using neutralization and specific ELISA assays

A Newly Engineered A549 Cell Line Expressing ACE2 and TMPRSS2 Is Highly Permissive to SARS-CoV-2, Including the Delta and Omicron Variants

Differential activation of human neutrophils by SARS-CoV-2 variants of concern

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