Less neutralization evasion of SARS-CoV-2 BA.2.86 than XBB sublineages and CH.1.1

Abstract

The highly mutated BA.2.86, with over 30 spike protein mutations in comparison to Omicron BA.2 and XBB.1.5 variants, has raised concerns about its potential to evade COVID-19 vaccination or prior SARS-CoV-2 infection-elicited immunity. In this study, we employ a live SARS-CoV-2 neutralization assay to compare the neutralization evasion ability of BA.2.86 with other emerged SARS-CoV-2 subvariants, including BA.2-derived CH.1.1, Delta-Omicron recombinant XBC.1.6, and XBB descendants XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1 and FL.1.5.1. Our results show that BA.2.86 is less neutralization evasive than XBB sublineages. XBB descendants XBB.1.16, EG.5.1, and FL.1.5.1 continue to significantly evade neutralization induced by the parental COVID-19 mRNA vaccine and a BA.5 Bivalent booster. Notably, when compared to XBB.1.5, the more recent XBB descendants, particularly EG.5.1, display increased resistance to neutralization. Among all the tested variants, CH.1.1 exhibits the greatest neutralization evasion. In contrast, XBC.1.6 shows a slight reduction but remains comparably sensitive to neutralization when compared to BA.5. Furthermore, a recent XBB.1.5-breakthrough infection significantly enhances the breadth and potency of cross-neutralization. These findings reinforce the expectation that the upcoming XBB.1.5 mRNA vaccine would likely boost the neutralization of currently circulating variants, while also underscoring the critical importance of ongoing surveillance to monitor the evolution and immune evasion potential of SARS-CoV-2 variants.

Keywords: BA.2.86; SARS-CoV-2; mRNA vaccine; neutralization; variants.

Figure 1.

Neutralization titres against Omicron sublineages. (A) FFRNT₅₀ of 28 sera collected after BA.5-bivalent booster from individuals without prior SARS-CoV-2 infection. (B) FFRNT₅₀ of 20 sera collected after BA.5-bivalent-booster from individuals with prior SARS-CoV-2 infection. (C) FFRNT₅₀ of 42 sera collected after XBB.1.5-breakthrough infection from individuals with parental mRNA vaccination. (D) FFRNT₅₀ of 19 sera collected after XBB.1.5-breakthrough infection from individuals with parental mRNA vaccination plus BA.5-bivalent booster. The solid lines and numeric values above each panel indicate the geometric mean titres (GMTs). The error bars represent the 95% confidence intervals (Cis). The fold reduction in GMT against each Omicron sublineage, compared with the GMT against USA-WA1/2020 or BA.5-spike, is shown in italic font. The green italic numbers indicate more sensitivity to neutralization. The dotted line indicates the limit of detection of FFRNT₅₀. FFRNT₅₀ of <20 was treated as 10 for plotting purposes and statistical analysis. The p values (determined using the Wilcoxon matched-pairs signed-rank test) for group comparison of GMTs are shown in Table S5.