SARS-CoV-2 Omicron spike mediated immune escape and tropism shift

Abstract

The Omicron variant emerged in southern Africa in late 2021 and is characterised by multiple spike mutations across all spike domains. Here we show that the Omicron spike confers very significant evasion of vaccine elicited neutralising antibodies that is more pronounced for ChAdOx-1 adenovirus vectored vaccine versus BNT162b2 mRNA vaccine. Indeed neutralisation of Omicron was not detectable for the majority of individuals who had received two doses of ChAdOx-1. Third dose mRNA vaccination rescues neutralisation in the short term. Despite three mutations predicted to favour spike S1/S2 cleavage, observed cleavage efficiency is lower than for wild type Wuhan-1 D614G and Delta. We demonstrate significantly lower infectivity of lung organoids and Calu-3 lung cells expressing endogenous levels of ACE2 and TMPRSS2 but similar infection as compared to Delta when using H1299 lung epithelial cells. Importantly, fusogenicity of the Omicron spike is impaired, leading to marked reduction in syncitia formation. These observations indicate that Omicron has gained immune evasion properties whilst possibly modulating properties associated with replication and pathogenicity.

Interpretable and Predictive Deep Modeling of the SARS-CoV-2 Spike Protein Sequence

“…The reduced severity of Omicron as compared to Delta is consistent with early laboratory evidence that there is a reduction in lower lung infectivity, deficient cell entry, and a reduction in syncytium formation due to reduced ability of the spike protein to mediate plasma membrane fusion. [178], [179] A decrease in severe disease is also consistent with preliminary clinical and epidemiological evidence that had emerged by the time of this manuscript's preparation, suggesting that patients had less severe disease in South Africa. [180] Reduced severe disease in South Africa may be due to a particularly high degree of seroprevalence in South Africa as a result of prior infection and vaccination of the vulnerable population.…”

“…However, the model’s predictions are consistent with the preliminary data showing that Omicron may have deficient cell entry and less induction of cell-cell fusion as compared to wild type (ancestral genome) as well as Delta. [178] It has also been suggested based on free energy calculations that the Omicron spike protein has deficient ACE2 binding as compared to wild type or Omicron. [182] Even if these and other preliminary results and predictions of lower severity on an individual basis bear out, epidemiological evidence clearly shows that Omicron is highly transmissible, significantly more so than Delta.…”

Direct Comparison of SARS-CoV-2 Nasal RT-PCR and Rapid Antigen Test (BinaxNOW™) at a Community Testing Site During an Omicron Surge

“…Omicron putatively has a shorter incubation period than prior variants. Symptoms are more intense in the upper respiratory track, and the virus appears to be less pathogenic in the lower airway compared to prior variants (11). One small study with five positive health care workers suggested detection is faster from oral versus nasal swabs (12).…”

Molecular basis of SARS-CoV-2 Omicron variant receptor engagement and antibody evasion and neutralization

“…With 37 mutations in its spike, this variant shows striking immune evasion while it also displays increased binding affinity with human ACE2 relative to the WT strain 15,16,28 . Recent reports also showed that the Omicron S exhibits reduced furin cleavage and less S1 shedding 45,46 . It is essential to understand how the mutations present in the Omicron S contribute to the higher transmissibility and immune escape observed for this threatening variant.…”