SARS-CoV-2 Omicron variant: Immune escape and vaccine development

Abstract

New genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constantly emerge through unmitigated spread of the virus in the ongoing Coronavirus disease 2019 pandemic. Omicron (B.1.1.529), the latest variant of concern (VOC), has so far shown exceptional spread and infectivity and has established itself as the dominant variant in recent months. The SARS-CoV-2 spike glycoprotein is a key component for the recognition and binding to host cell angiotensin-converting enzyme 2 receptors. The Omicron variant harbors a cluster of substitutions/deletions/insertions, and more than 30 mutations are located in spike. Some noticeable mutations, including K417N, T478K, N501Y, and P681H, are shared with the previous VOCs Alpha, Beta, Gamma, or Delta variants and have been proven to be associated with higher transmissibility, viral infectivity, and immune evasion potential. Studies have revealed that the Omicron variant is partially resistant to the neutralizing activity of therapeutic antibodies and convalescent sera, which poses significant challenges for the clinical effectiveness of the current vaccines and therapeutic antibodies. We provide a comprehensive analysis and summary of the epidemiology and immune escape mechanisms of the Omicron variant. We also suggest some therapeutic strategies against the Omicron variant. This review, therefore, aims to provide information for further research efforts to prevent and contain the impact of new VOCs during the ongoing pandemic.

Keywords: Omicron variant; immune escape; spike; vaccine development.

FIGURE 1

The estimated proportion curve of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Delta variant and Omicron variant in total samples. The proportion curve of Delta (A) and Omicron (B) cases were shown weekly from November 8, 2021, to January 24, 2022, in six countries (South Africa, India, Brazil, the United States, France, and the United Kingdom). Proportion is relative to all samples collected. Data were obtained from GISAID and accessed on February 12, 2022.

FIGURE 2

The schematic representation of the mutations in the spike protein of five SARS‐CoV‐2 variants of concern (VOCs). Mutation data were from CoVariants. The same and similar mutations (red word) among those VOCs are highlighted. Omicron variant mutations are based on 21K or BA.1. RBD, receptor‐binding domain

FIGURE 3

The impaired inhibition of neutralizing antibodies against Omicron variant infection. (A) Two cell entry pathways of SARS‐CoV‐2 Omicron. Left is the plasma membrane pathway using transmembrane protease serine type 2 and right is the endocytic pathway. (B) The immune evasion of Omicron from neutralizing antibodies. (1) Neutralizing antibodies from individuals prevent the wild‐type (WT) SARS‐CoV‐2 viruses into host cells by neutralizing viruses. The Omicron variant largely escaped neutralization by convalescent and vaccinated sera; therefore, viruses successfully entered into host cells by binding to the angiotensin‐converting enzyme 2 receptor

FIGURE 4

The protective effects of Coronavirus disease 2019 (COVID‐19) booster vaccines. (A) Antibodies produced by two doses of COVID‐19 vaccine showed effective protection against WT SARS‐CoV‐2 virus but reduced protection against Omicron variant between 14 days to 6 months after the second dose of vaccine. After the full vaccination, the protective effects decreased against both WT SARS‐CoV‐2 virus and Omicron variant. (B), (C) the heterologous booster (C) evaluated higher protective effects against both WT SARS‐CoV‐2 virus and Omicron variant than the homologous booster (B)