Lung cell entry, cell–cell fusion capacity, and neutralisation sensitivity of omicron sublineage BA.2.75

Arora, Prerna; Nehlmeier, Inga; Kempf, Amy; Cossmann, Anne; Schulz, Sebastian; Dopfer-Jablonka, Alexandra; Baier, Eva; Tampe, Björn; Moerer, Onnen; Dickel, Steffen; Winkler, Martin Sebastian; Jäck, Hans‐Martin; Behrens, Georg; Pöhlmann, Stefan; Hoffmann, Markus

doi:10.1016/s1473-3099(22)00591-6

Cited by 17 publications

(9 citation statements)

References 11 publications

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“…BA.4 and BA.5 replicate more efficiently than BA.2 in alveolar epithelial cells and are more fusogenic 50 . BA.2.75.2 growth efficiency in alveolar epithelial cells and spike-mediated fusion in Calu-3 cells are also higher than those of BA.2 51,52 . We did not observe an enhanced cell-cell fusogenicity of BA.2.75.2, BA.4.6.…”

Section: Discussionmentioning

confidence: 80%

Resistance of Omicron subvariants BA.2.75.2, BA.4.6, and BQ.1.1 to neutralizing antibodies

et al. 2023

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Convergent evolution of SARS-CoV-2 Omicron BA.2, BA.4, and BA.5 lineages has led to the emergence of several new subvariants, including BA.2.75.2, BA.4.6. and BQ.1.1. The subvariant BQ.1.1 became predominant in many countries in December 2022. The subvariants carry an additional and often redundant set of mutations in the spike, likely responsible for increased transmissibility and immune evasion. Here, we established a viral amplification procedure to easily isolate Omicron strains. We examined their sensitivity to 6 therapeutic monoclonal antibodies (mAbs) and to 72 sera from Pfizer BNT162b2-vaccinated individuals, with or without BA.1/BA.2 or BA.5 breakthrough infection. Ronapreve (Casirivimab and Imdevimab) and Evusheld (Cilgavimab and Tixagevimab) lose antiviral efficacy against BA.2.75.2 and BQ.1.1, whereas Xevudy (Sotrovimab) remaine weakly active. BQ.1.1 is also resistant to Bebtelovimab. Neutralizing titers in triply vaccinated individuals are low to undetectable against BQ.1.1 and BA.2.75.2, 4 months after boosting. A BA.1/BA.2 breakthrough infection increases these titers, which remains about 18-fold lower against BA.2.75.2 and BQ.1.1, than against BA.1. Reciprocally, a BA.5 breakthrough infection increases more efficiently neutralization against BA.5 and BQ.1.1 than against BA.2.75.2. Thus, the evolution trajectory of novel Omicron subvariants facilitates their spread in immunized populations and raises concerns about the efficacy of most available mAbs.

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Section: Discussionmentioning

confidence: 80%

Resistance of Omicron subvariants BA.2.75.2, BA.4.6, and BQ.1.1 to neutralizing antibodies

et al. 2023

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“…BA.4 and BA.5 replicate more efficiently than BA.2 in alveolar epithelial cells and are more fusogenic 48 . BA.2.75.2 growth efficiency in alveolar epithelial cells and spike-mediated fusion in Calu-3 cells are also higher than those of BA.2 49,50 . We did not observe an enhanced cell-cell fusogenicity of BA.2.75.2, BA.4.6.…”

Section: Discussionmentioning

confidence: 80%

Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

Planas

Bruel

Staropoli

et al. 2022

Preprint

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Convergent evolution of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 lineages has led to the emergence of several new subvariants, including BA.2.75.2, BA.4.6. and BQ.1.1. The subvariants BA.2.75.2 and BQ.1.1 are expected to become predominant in many countries in November 2022. They carry an additional and often redundant set of mutations in the spike, likely responsible for increased transmissibility and immune evasion. Here, we established a viral amplification procedure to easily isolate Omicron strains. We examined their sensitivity to 6 therapeutic monoclonal antibodies (mAbs) and to 72 sera from Pfizer BNT162b2-vaccinated individuals, with or without BA.1/BA.2 or BA.5 breakthrough infection. Ronapreve (Casirivimab and Imdevimab) and Evusheld (Cilgavimab and Tixagevimab) lost any antiviral efficacy against BA.2.75.2 and BQ.1.1, whereas Xevudy (Sotrovimab) remained weakly active. BQ.1.1 was also resistant to Bebtelovimab. Neutralizing titers in triply vaccinated individuals were low to undetectable against BQ.1.1 and BA.2.75.2, 4 months after boosting. A BA.1/BA.2 breakthrough infection increased these titers, which remained about 18-fold lower against BA.2.75.2 and BQ.1.1, than against BA.1. Reciprocally, a BA.5 breakthrough infection increased more efficiently neutralization against BA.5 and BQ.1.1 than against BA.2.75.2. Thus, the evolution trajectory of novel Omicron subvariants facilitated their spread in immunized populations and raises concerns about the efficacy of most currently available mAbs.

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“…3B). Compared to human reference data 36, 37 ( N = 23), the neutralising antibody activity of the cohort of 19 macaques was weaker (Wilcoxon rank sum test, Z = 2.63, P = 0.0086, two-tailed) (Fig. 3C).…”

Section: Resultsmentioning

confidence: 75%

“…Each colour represents one subject. ( C ) Serum NT50 for the SARS-CoV-2 B.1 lineage in macaques compared to human reference data 36,37 . ( D – F ) Serum neutralising activity for the SARS-CoV-2 BA.4/BA.5 lineage.…”

Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 vaccination of laboratory rhesus monkeys (Macaca mulatta): Monitoring and efficacy

Grothe

Lukaß

et al. 2022

Preprint

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The availability of effective vaccines and a high vaccination rate allowed the recent mitigation, or even withdrawal, of many protective measures for containing the SARS CoV-2 pandemic. At the same time, new and highly mutated variants of the virus are found to have significantly higher transmissibility and reduced vaccine efficacy, thus causing high infection rates during the third year of the pandemic. The combination of reduced measures and increased infectivity poses a particular risk for unvaccinated individuals, including animals susceptible to the virus. Among the latter, non-human primates (NHPs) are particularly vulnerable. They serve as important models in various fields of biomedical research and because of their cognitive capabilities, they receive particular attention in animal welfare regulations around the world. Yet, although they played an extraordinarily important role for developing and testing vaccines against SARS-CoV-2, the protection of captive rhesus monkeys against Covid-19 has rarely been discussed. We here report upon twofold mRNA vaccination of a cohort of 19 rhesus monkeys (Macaca mulatta) against infection by SARS-CoV-2. All animals were closely monitored on possible side effects of vaccination, and were tested for neutralising antibodies against the virus. The data show that vaccination of rhesus monkeys is a safe and reliable measure to protect these animals against SARS-CoV-2.

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Lung cell entry, cell–cell fusion capacity, and neutralisation sensitivity of omicron sublineage BA.2.75

Cited by 17 publications

References 11 publications

Resistance of Omicron subvariants BA.2.75.2, BA.4.6, and BQ.1.1 to neutralizing antibodies

Resistance of Omicron subvariants BA.2.75.2, BA.4.6, and BQ.1.1 to neutralizing antibodies

Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

SARS-CoV-2 vaccination of laboratory rhesus monkeys (Macaca mulatta): Monitoring and efficacy

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