The significant immune escape of pseudotyped SARS-CoV-2 variant Omicron

Abstract

The emergence of Omicron/BA.1 has brought new challenges to fight against SARS-CoV-2. A large number of mutations in the Spike protein suggest that its susceptibility to immune protection elicited by the existing COVID-19 infection and vaccines may be altered. In this study, we constructed the pseudotyped SARS-CoV-2 variant Omicron. The sensitivity of 28 serum samples from COVID-19 convalescent patients infected with SARS-CoV-2 original strain was tested against pseudotyped Omicron as well as the other variants of concern (VOCs, Alpha, Beta, Gamma, Delta) and variants of interest (VOIs, Lambda, Mu). Our results indicated that the mean neutralization ED50 of these sera against Omicron decreased to 66, which is about 8.4-folds compared to the D614G reference strain (ED50 = 556), whereas the neutralization activity of other VOC and VOI pseudotyped viruses decreased only about 1.2-4.5-folds. The finding from our in vitro assay suggest that Omicron variant may lead to more significant escape from immune protection elicited by previous SARS-CoV-2 infection and perhaps even by existing COVID-19 vaccines.

Keywords: BA.1; SARS-CoV-2; VOC; convalescence serum; neutralization.

Figure 1.

A. Schematic Illustration of Omicron Spike. All of the 32 mutations were located on Omicron Spike, which was used to construct the pseudotyped Omicron virus. B–H. The neutralization analysis of convalescent sera against Omicron, VOCs and VOIs. The neutralization activity of 28 convalescent sera from COVID-19 patients was tested. The neutralization ED50 and ratio compared to the reference strain D614G was also displayed as indicated. Data represented ED50 of three independent experiments. I. The comparison of neutralization activity against different VOCs and VOIs. J–K. The neutralization sensitivity of sera collected from convalescent patients at different time point against Omicron. The neutralization ED50 and ratio compared to the reference strain D614G was also displayed as indicated. Data represented ED50 of three independent experiments. J sera were collected 1-month after recovery; K, sera were collected 3-month after recovery; L. The heatmap of individual neutralization data. Data represented ED50 of three independent experiments. The Red to blue colour represented ED50 high to low as shown in the scale bar. CS1–15 sera were collected 1-month after recovery; CS16–28 sera were collected 3-month after recovery.