A comparative study of spike protein of SARS-CoV-2 and its variant Omicron (B.1.1.529) on some immune characteristics

Abstract

The emergence of Omicron variant raises great concerns because of its rapid transmissibility and its numerous mutations in spike protein (S-protein). S-protein can act as a pathogen-associated molecular pattern and complement activator as well as antigen. We compared some immune characteristics of trimer S-proteins for wild type (WT-S) and B.1.1.529 Omicron (Omicron-S) to investigate whether the mutations have affected its pathogenicity and antigenic shift. The results indicated that WT-S and Omicron-S directly activated nuclear factor-κB (NF-κB) and induced the release of pro-inflammatory cytokines in macrophages, but the actions of Omicron-S were weaker. These inflammatory reactions could be abrogated by a Toll-like receptor 4 antagonist TAK-242. Two S-proteins failed to induce the production of antiviral molecular interferon-β. In contrast to pro-inflammatory effects, the ability of two S-proteins to activate complement was comparable. We also compared the binding ability of two S-proteins to a high-titer anti-WT-receptor-binding domain antibody. The data showed that WT-S strongly bound to this antibody, while Omicron-S was completely off-target. Collectively, the mutations of Omicron have a great impact on the pro-inflammatory ability and epitopes of S-protein, but little effect on its ability to activate complement. Addressing these issues can be helpful for more adequate understanding of the pathogenicity of Omicron and the vaccine breakthrough infection.

SARS-CoV-2 Variants Show Different Host Cell Proteome Profiles With Delayed Immune Response Activation in Omicron-Infected Cells

“…In addition, Omicron BA.1 infected patients showed a low systemic inflammatory response compared to patients infected with previous SARS-CoV-2 variants ( 44 ). Mechanistically, the direct comparison of the B.1 S protein with the BA.1 S protein revealed that the BA.1 S protein induced less activation of immune modulators, such as NF-κB ( 45 ).…”

Exploring the immunogenic properties of SARS-CoV-2 structural proteins: PAMP:TLR signaling in the mediation of the neuroinflammatory and neurologic sequelae of COVID-19

“…Most studies of SARS-CoV-2 structural proteins have been conducted in vitro using an array of human and mouse cells. Both the S protein or it’s S1 subunit is sufficient to elicit a proinflammatory immune response in primary cells and cell lines including human lung cells ( Forsyth et al, 2022 , Khan et al, 2021 , Patra et al, 2020 ), human endothelial cells ( Perico et al, 2022 ), human intestinal epithelial cells ( Forsyth et al, 2022 ), HL-60 cells ( Zhao et al, 2021 ), human monocytes/macrophages ( Karwaciak et al, 2021 , Khan et al, 2021 , Pantazi et al, 2021 , Schroeder and Bieneman, 2022 , Shirato and Kizaki, 2021 , Zhao et al, 2021 ), mouse macrophages ( Li et al, 2022 , Shirato and Kizaki, 2021 , Zhao et al, 2021 ), human peripheral blood mononuclear cells ( Olajide et al, 2021b ), and TF1PIGA null cells ( Yu et al, 2020 ). Interestingly, Zhao and colleagues examined the proinflammatory effects of different domains of the S protein and found that the N-terminal (NT) and receptor binding (RB) domains (D) failed to elicit a proinflammatory cytokine response.…”

“…However, Li et al conducted a comparison of the proinflammatory properties between the S protein of the original isolate and the Omicron (B.1.1.529) variant. They found that the Omicron S variant produced a weaker inflammatory response compared to the original isolate ( Li et al, 2022 ). Otherwise, it is largely unknown to what extent mutations in the S and S1 subunit of variants affect the proinflammatory properties of these proteins.…”

“…However, unlike Khan et al, we found that the S2 subunit failed to elicit a proinflammatory response in both HEK TLR2 and TLR4 cell lines ( Frank et al, 2022 ). Conversely, Li et al found that a TLR4 receptor antagonist blocked the proinflammatory effects of the S protein, whereas a TLR2 receptor antagonist failed to block these effects in RAW264.7 cells ( Li et al, 2022 ). Olajide et al also found that a TLR4 receptor antagonist as well as TLR4 siRNA blocked the proinflammatory effects of the S1 subunit in BV-2 microglial cells ( Olajide et al, 2021a ).…”

Effects of Different Types of Recombinant SARS-CoV-2 Spike Protein on Circulating Monocytes Structure

“…Succinctly, we typically found larger alterations in samples challenged with 20 ng/mL of the recombinant protein as compared to those where the lower 2 ng/mL concentration was added, as well as in those especially challenged with SARS-CoV-2 recombinant spike protein of the Alpha and Delta variants. Thus, it is conceivable that the sequence and structure of these two spike protein variants may display better affinity for some receptors expressed at monocyte surface and/or may be capable to more intensely trigger monocyte activation and injury compared to the Omicron spike protein, as was earlier conjectured [35]. The lower chemical stability of the Omicron spike protein compared to the spike protein of former variants the has also been suggested as an important characteristic that may explain the lower pathogenetic burden of this strain [36].…”