Study characterizes SARS-CoV-2 Omicron BA.2.86: New variant under watch

In a recent article posted to the bioRxiv* server, researchers performed an experimental assessment of the antigenicity and infectivity of BA.2.86, a newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) saltation variant designated as a variant under monitoring (VUM) by the World Health Organization (WHO) on August 18, 2023.

Study: Antigenicity and infectivity characterization of SARS-CoV-2 BA.2.86. Image Credit: JBArt / ShutterstockStudy: Antigenicity and infectivity characterization of SARS-CoV-2 BA.2.86. Image Credit: JBArt / Shutterstock

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

So far, researchers have detected only 24 genomic sequences of BA.2.86; however, notably, they originated in individuals in multiple countries with no travel history. While BA.2.86 sequences might not be of any epidemiological relevance, this variant exhibits the potential for global spread. Furthermore, BA.2.86 harbors many more mutations than its predecessors, BA.2 and XBB.1.5, suggesting its distinct antigenicity.

Mutations that mediate its enhanced resistance to convalescent plasma from XBB breakthrough infection (BTI) and reinfections are nested inside the receptor-binding domain (RBD) of its spike (S) glycoprotein. In addition, mutations in BA.2.86's N-terminal domain (NTD) and sub-domain 1 (SD1) contribute to its enhanced resistance. 

It seems like BA.2.86 has traded off its infectivity for acquiring higher immune evading capabilities during evolution, which calls for close monitoring.

About the study

In the present study, researchers first developed a BA.2.86 pseudovirus and then determined its antigenic distance from wildtype (WT) and other preceding SARS-CoV-2 variants, including Omicron sublineages, BA.5, BQ.1.1, and XBB.

Further, they evaluated the immunity-evading capabilities of BA.2.86 pseudovirus. To this end, they performed pseudovirus neutralization assays using plasma samples from two groups and against a monoclonal antibodies (mAbs) panel. 

The first group comprised 27 individuals who experienced XBB BTI only once after vaccination, and the second group had 54 convalescents who contracted XBB (re)infection after BTI from BA.5/BF.7. All participants had received three doses of an inactivated coronavirus disease 2019 (COVID-19) vaccine before XBB BTI.

Furthermore, the team delineated the key RBD mutations of BA.2.86 from that found in XBB.1.5, for which they tested a panel of neutralizing antibodies (nAbs) against XBB.1.5-based pseudoviruses carrying one BA.2.86 RBD mutation. Finally, the team evaluated the cellular infectivity of BA.2.86 by testing the efficacy of its pseudovirus form in infecting hACE2-HEK293T cell lines.

Results

BA.2.86 showed a pronounced antigenic drift from WT, BA.2/BA.5, and XBB.1.5 SARS-CoV-2 variants, suggesting it could strongly evade XBB-induced antibodies. It also exhibited exceptionally high resistance in neutralization assays across all vaccinated groups.

Interestingly, BA.2.86's immune evading potential exceeded EG.5 but was comparable to Omicron's "FLip" variant HK.3, a double mutant with L455F & F456L combination mutations. Despite their comparable level of immune evasion, the relative activities of HK.3 and BA.2.86 varied across samples, indicating their antigenic distance. Further, BA.2.86 induced markedly higher antibody evasion against XBB-stimulated plasma. Except for SA55, other mAbs tested in this study failed to neutralize BA.2.86.

Importantly, the E554K mutation in combination with XBB.1.5 mutations enhanced plasma evasion of BA.2.86, suggesting that SD1- targeting nAbs majorly constitute XBB-stimulated convalescent plasma. Furthermore, BA.2.86's NTD mutations enhanced its neutralizing evasion.

In pseudovirus assays, relative to XBB.1.5 and EG.5.1/EG.5, BA.2.86 exhibited the lowest infectivity. The authors noted that K356T, V483del, and E554K mutations mainly contributed to its lower infectivity. Specifically, K356T introduced an N-linked glycosylation motif for amino acid site N354, and V483del was close to angiotensin-converting enzyme 2 (ACE2)-binding sites, with both events affecting viruses' host cell entry efficacy.

The researchers measured BA.2.86 infectivity through pseudovirus assays; thus, these results require further validation using authentic isolates. 

Conclusion

The study data suggested that BA.2.86 exhibited exceptional immunity-evading potential compared to currently circulating SARS-CoV-2 Omicron variants. Furthermore, BA.2.86 was antigenically farther from all Omicron variants tested and could escape XBB-induced nAbs, i.e., resist XBB-elicited humoral immunity and XBB-effective mAbs.

Even though, at present, it seems that BA.2.86 might not prevail due to its lower infectiousness. However, if it further mutates during host-viral evolution and transmission, it might enhance its infectivity. Given its potential to become a predominant SARS-CoV-2 variant shortly, like Omicron's XBB subvariants, global cooperation would be necessary to chart the BA.2.86 evolution over time. 

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Preliminary scientific report. Antigenicity and infectivity characterization of SARS-CoV-2 BA.2.86, Sijie Yang, Yuanling Yu, Fanchong Jian, Weiliang Song, Ayijiang Yisimayi, Xiaosu Chen, Yanli Xu, Peng Wang, Lingling Yu, Jing Wang, Xiao Niu, Jing Wang, Tianhe Xiao, Ran An, Yao Wang, Qingqing Gu, Fei Shao, Ronghua Jin, Zhongyang Shen, Youchun Wang, Yunlong Richard Cao, bioRxiv 2023.09.01.555815; doi: https://doi.org/10.1101/2023.09.01.555815https://www.biorxiv.org/content/10.1101/2023.09.01.555815v1
Neha Mathur

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.

Citations

Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Mathur, Neha. (2023, September 06). Study characterizes SARS-CoV-2 Omicron BA.2.86: New variant under watch. News-Medical. Retrieved on June 25, 2024 from https://www.news-medical.net/news/20230906/Study-characterizes-SARS-CoV-2-Omicron-BA286-New-variant-under-watch.aspx.

  • MLA

    Mathur, Neha. "Study characterizes SARS-CoV-2 Omicron BA.2.86: New variant under watch". News-Medical. 25 June 2024. <https://www.news-medical.net/news/20230906/Study-characterizes-SARS-CoV-2-Omicron-BA286-New-variant-under-watch.aspx>.

  • Chicago

    Mathur, Neha. "Study characterizes SARS-CoV-2 Omicron BA.2.86: New variant under watch". News-Medical. https://www.news-medical.net/news/20230906/Study-characterizes-SARS-CoV-2-Omicron-BA286-New-variant-under-watch.aspx. (accessed June 25, 2024).

  • Harvard

    Mathur, Neha. 2023. Study characterizes SARS-CoV-2 Omicron BA.2.86: New variant under watch. News-Medical, viewed 25 June 2024, https://www.news-medical.net/news/20230906/Study-characterizes-SARS-CoV-2-Omicron-BA286-New-variant-under-watch.aspx.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment
Post

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Curcuminoid compounds show promise against COVID-19 in neuronal cells