Potential immune evasion of the severe acute respiratory syndrome coronavirus 2 Omicron variants

Abstract

Coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global pandemic. The Omicron variant (B.1.1.529) was first discovered in November 2021 in specimens collected from Botswana, South Africa. Omicron has become the dominant variant worldwide, and several sublineages or subvariants have been identified recently. Compared to those of other mutants, the Omicron variant has the most highly expressed amino acid mutations, with almost 60 mutations throughout the genome, most of which are in the spike (S) protein, especially in the receptor-binding domain (RBD). These mutations increase the binding affinity of Omicron variants for the ACE2 receptor, and Omicron variants may also lead to immune escape. Despite causing milder symptoms, epidemiological evidence suggests that Omicron variants have exceptionally higher transmissibility, higher rates of reinfection and greater spread than the prototype strain as well as other preceding variants. Additionally, overwhelming amounts of data suggest that the levels of specific neutralization antibodies against Omicron variants decrease in most vaccinated populations, although CD4⁺ and CD8⁺ T-cell responses are maintained. Therefore, the mechanisms underlying Omicron variant evasion are still unclear. In this review, we surveyed the current epidemic status and potential immune escape mechanisms of Omicron variants. Especially, we focused on the potential roles of viral epitope mutations, antigenic drift, hybrid immunity, and "original antigenic sin" in mediating immune evasion. These insights might supply more valuable concise information for us to understand the spreading of Omicron variants.

Keywords: Omicron variant; SARS-CoV-2; hybrid immunity; immune evasion; original antigenic sin.

Figure 1

The schematic representation of the mutations in protein of five SARS-CoV-2 variants of concern (VOCs). (A) Reported essential mutations in the S-glycoprotein of SARS-CoV-2 variants. (B) Reported critical mutations in the N, M and E proteins of SARS-CoV-2 variants. Data are from WHO (Coronavirus disease (COVID-19): Variants of SARS-COV-2, https://www.who.int/news-room/). NTD, N-terminal domain; CTD, C-terminal domain; LKR, Central linker region; SP, Signal peptide; RBD, Receptor-binding structural domain; RBM, Receptor-binding motif; FP, Fusion peptide; HR1, Heptapeptide repeat 1; HR2, Heptapeptide repeat 2; TM, Transmembrane structural domain; CT, Cytoplasmic tail. WT, Wuhan-Hu-1 strain.

Figure 2

The potential immune escape mechanism of Omicron variants. Lots of immunodominant epitopes are found in the prototype of SARS-CoV-2 (Wuhan-Hu-1) and the first generation of COVID-19 Vaccines which developed are based on the S-glycoprotein of SARS-CoV-2 (common epitopes), these common epitopes can activate naïve T cells and finally differentiate into memory T cells in persons who are suffered from Wuhan-Hu-1 infection or got COVID-19 vaccination. The Omicron variants also have some of these common epitopes, which might also rapidly activate the memory T cells to release inflammatory factors, by thus induce immune damage and immune evasion. However, if the amino acid mutations of Omicron variants are taken place in these common epitopes, these epitopes are possibly unable to activate memory T cells and finally induce immune escape (escape epitopes). Furthermore, if the amino acid mutations are found in some places where leads to the formation of some novel epitopes (mutated epitopes), these mutated epitopes might activate naïve T cells and control Omicron variants spread, thereafter induce immune protection.