Neutralization against Omicron SARS-CoV-2 from previous non-Omicron infection

Abstract

The spread of the Omicron SARS-CoV-2 variant underscores the importance of analyzing the cross-protection from previous non-Omicron infection. We have developed a high-throughput neutralization assay for Omicron SARS-CoV-2 by engineering the Omicron spike gene into an mNeonGreen USA-WA1/2020 SARS-CoV-2 (isolated in January 2020). Using this assay, we determine the neutralization titers (defined as the maximal serum dilution that inhibited 50% of infectious virus) of patient sera collected at 1- or 6-months after infection with non-Omicron SARS-CoV-2. From 1- to 6-month post-infection, the neutralization titers against USA-WA1/2020 decrease from 601 to 142 (a 4.2-fold reduction), while the neutralization titers against Omicron-spike SARS-CoV-2 remain low at 38 and 32, respectively. Thus, at 1- and 6-months after non-Omicron SARS-CoV-2 infection, the neutralization titers against Omicron are 15.8- and 4.4-fold lower than those against USA-WA1/2020, respectively. The low cross-neutralization against Omicron from previous non-Omicron infection supports vaccination of formerly infected individuals to mitigate the health impact of the ongoing Omicron surge.

Fig. 1. Reduced neutralization of Omicron SARS-CoV-2 by previous non-Omicron viral infection.

50% fluorescent focus reduction neutralization titers (FFRNT₅₀) were measured for two serum panels from patients previously infected with non-Omicron SARS-CoV-2. The first serum panel was collected at 1-month post-infection (n = 64) and the second panel collected at 6-months post-infection (n = 36). For each serum, FFRNT₅₀ values were determined against mNG USA-WA1/2020 (in gray color) and Omicron-spike SARS-CoV-2 (in red color). a FFRNT₅₀s of 1-month postinfection sera (shown as circles). b FFRNT₅₀s of 6-month postinfection sera (shown as triangles). Supplementary Tables 1 and 2 summarize the FFRNT₅₀ values and serum information for (a) and (b), respectively. Each symbol of dots (a) and triangles (b) represents one serum specimen. The FFRNT₅₀ value for each serum was determined in duplicate assays and is presented as the geometric mean. The bar heights and the numbers above each set of data indicate geometric mean titers. The whiskers indicate 95% confidence intervals. The dotted line indicates the first serum dilution (1:20) of the FFRNT assay. The FFRNT₅₀ values of sera that did not show any inhibition of viral infection are presented as 10 for plot purposes and statistical analysis. Statistical analysis was performed using the Wilcoxon matched-pairs signed-rank test. The statistical significance of the difference between the geometric mean titers against USA-WA1/2020 and Omicron-spike SARS-CoV-2 is p < 0.0001 in both (a) and (b).