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. Among all the tested variants, CH.1.1 exhibits the greatest neutralization evasion. In comparison to XBB.1.5, the more recent XBB descendants, particularly EG.5.1 and FL.1.5.1, display increased resistance to neutralization induced by parental COVID-19 mRNA vaccine and a BA.5-Bivalent-booster. In contrast, XBC.1.6 shows a slight reduction but remains comparable sensitivity 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.

Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion

“…Six months after the boost, the efficacy of the sera against EG.5.1.3 and BA.2.86.1/JN.1 was barely detectable. This confirms reports indicating that these two variants are among the most immune evasive viruses described so far, even if some variations between studies have been observed 16,[21][22][23][24][25][26][27][28][29][30] .…”

“…XBB.1.16.1 and EG.5.1.3 neutralization titers were the lowest (22 and 30-fold lower than BA.1, respectively). BA.2.86.1 neutralization was about 2-fold more sensitive to neutralization than EG.5.1.3, confirming recent results 16,[21][22][23][24][25][26][27][28][29][30] .…”

“…The impact of this unprecedented combination of mutations on antibody evasion has started to be deciphered. A few recent articles and preprints reported that NAb responses to BA.2.86 are lower than BA.2, but comparable or slightly higher than to other simultaneously circulating XBB-derived variants 16,[21][22][23][24][25][26][27][28][29][30][31]20 . Most of these studies were performed with lentiviral or VSV pseudotypes.…”

A deep learning framework for predicting the neutralizing activity of COVID-19 therapeutics and vaccines against evolving SARS-CoV-2 variants

“…Our findings indicate that the model can accurately predict the impact of new spike protein mutants on the neutralization activity of therapeutics and vaccines (R 2 = 0.77), making it a valuable tool for identifying emerging viral variants that are likely to evade current COVID-19 treatments Our model's predictions for emerging SARS-CoV-2 lineages align with current research findings. Consistent with recent data, [27][28][29] the model predicts that the newer XBB descendants, specifically EG.5, FL.1.5.1, and XBB.1.16, have significantly reduced in vitro susceptibility to both vaccines and monoclonal antibodies, rising concerns for evading vaccine-driven immunity and lack of efficacy to clinically relevant monoclonal antibodies. On further analysis of mutations linked to reduced responsiveness, our model identifies the spike mutation F456L, present in EG.5 and FL.1.5.1, as a primary contributor to reduced neutralization by selected COVID-19 antibodies and vaccines.…”

“…On August 17, 2023, the World Health Organization (WHO) designated BA.2.86, a highly mutated subvariant originating from BA.2, as a variant under monitoring due to potential immune evasion risks. However, recent studies employing live and pseudovirus neutralization assays indicate that BA.2.86 elicits a higher neutralizing antibody response to mRNA bivalent boosters than newer XBB descendants, 27,29,32 though slightly lower than its parental lineage (BA.2). Despite over 30 amino acid mutations in its spike region compared to the parental lineage (BA.2), 32 many of which are novel to both the VAE and neural network, our model accurately predicted BA.2.86's behavior, underscoring its performance in emerging lineages.…”