key: cord-0945474-bkiobjex
authors: Zou, Jing; Kurhade, Chaitanya; Xia, Hongjie; Liu, Mingru; Xie, Xuping; Ren, Ping; Shi, Pei-Yong
title: Cross-neutralization of Omicron BA.1 against BA.2 and BA.3 SARS-CoV-2
date: 2022-03-31
journal: bioRxiv
DOI: 10.1101/2022.03.30.486409
sha: e493e95e99c45d3b4584e9d5fb744b9afe13fd1f
doc_id: 945474
cord_uid: bkiobjex

The Omicron SARS-CoV-2 has three distinct sublineages, among which sublineage BA.1 is responsible for the initial Omicron surge and is now being replaced by BA.2 world-wide, whereas BA.3 is currently at a low frequency. The ongoing BA.1-to-BA.2 replacement underscores the importance to understand the cross-neutralization among the three Omicron sublineages. Here we tested the neutralization of BA.1-infected human sera against BA.2, BA.3, and USA/WA1-2020 (a strain isolated in late January 2020). The BA.1-infected sera neutralized BA.1, BA.2, BA.3, and USA/WA1-2020 SARS-CoV-2s with geometric mean titers (GMTs) of 445, 107, 102, and 16, respectively. Thus, the neutralizing GMTs against heterologous BA.2, BA.3, and USA/WA1-2020 were 4.2-, 4.4-, and 28.4-fold lower than the GMT against homologous BA.1, respectively. These findings have implications in COVID-19 vaccine strategy.

surge. Third, vaccine-mediated T cell immunity and non-neutralizing antibodies that mediate antibody-dependent cytotoxicity could also confer protection against severe COVID-19. After vaccination or infection, the majority of T cell epitopes are highly preserved against Omicron spikes 7 . In agreement with this notion, 3 doses of BNT162b2 conferred efficacy against Omicron disease, but the protection wanes over time, with overall efficacy remaining high up to 6 months after dose 3 [8] [9] [10] [11] [12] . The real-world vaccine effectiveness and laboratory studies will guide vaccine booster strategy to achieve optimal breadth and duration of protection. cell monolayer in 96-well plates. After 1 h infection, the inoculum was aspirated and overlay medium (100 μ l supplemented with 0.8% methylcellulose) was added to each well. After incubating the plates at 37°C for 16-18 h, raw images of mNG foci were acquired using Cytation TM 7 (BioTek). The foci in each well were counted and normalized to the no-serum-treated controls to calculate infection rates. The FFRNT 50 value was defined as the minimal serum dilution that suppressed >50% of fluorescent foci. The neutralization titer of each serum was determined in duplicates, and the geometric mean was presented. FFRNT 50 of <20 was treated as 10 for plot purpose and statistical analysis. Tables 1 summarizes the FFRNT 50 results.

Statistics. The nonparametric Wilcoxon matched-pairs signed rank test was used to analyze the statistical significance in Figure 1B .

The data that support the findings of this study are available from the corresponding authors upon request. *Individual FFRNT 50 value is the geometric mean of duplicate plaque assay results. ^FFRNT 50 of <20 was treated as 10 for plot purpose and statistical analysis. $ NA: not available. # Geometric mean neutralizing titers (GMT). † 95% confidence interval (95% CI) for the GMT.

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C) FFRNT 50 values with connected lines for individual sera. Two sera exhibiting slightly higher FFRNT 50 s against BA.2 virus than that against BA.1-spike SARS-CoV-2 are indicated by symbol * (serum ID 1 and 2 in Table 1)