Virus isolation and neutralisation of SARS-CoV-2 variants BA.2.86 and EG.5.1.

In late July, 2023, SARS-CoV-2 surveillance programmes identified a new, highly mutated omicron subvariant, BA.2.86.1Rasmussen M Møller FT Gunalan V et al.First cases of SARS-CoV-2 BA.2.86 in Denmark, 2023.Euro Surveill. 2023; 282300460Crossref Scopus (4) Google Scholar Initial estimates place the effective reproduction number of BA.2.86 at 1·29-times greater than that of XBB.1.5 and near equivalent to that of EG.5.1, one of the most rapidly expanding XBB subvariants.2Uriu K Ito J Kosugi Y et al.Transmissibility, infectivity, and immune evasion of the SARS-CoV-2 BA.2.86 variant.Lancet Infect Dis. 2023; 23: 460-461Summary Full Text Full Text PDF Scopus (0) Google Scholar Since the emergence of BA.2.86, multiple countries have reported its presence, including an outbreak in a British care home, with an attack rate above 85%, where the majority of infected residents had received a SARS-CoV-2 Beta variant-based subunit vaccine 4 months earlier.3Reeve L Tessier E Trindall A et al.High attack rate in a large care home outbreak of SARS-CoV-2 BA.2.86, East of England, August 2023.Euro Surveill. 2023; 282300489Crossref Scopus (0) Google Scholar Relative to the SARS-CoV-2 index strain, the BA.2.86 spike protein has 60 amino acid changes, located predominantly in the N-terminal and receptor binding domains (figure A). Of these, 26 amino acid changes are distinct to BA.2.86 (figure B). This variation is anticipated to modulate the spike-mediated infectivity and antigenicity of BA.2.86. To test these hypotheses, we investigated the ability of BA.2.86 to infect different immortalised cell lines from clinical sample material and evaluated serum neutralisation for virus isolates. From clinical sample material, BA.2.86 established an infection in human-derived cell lines CaLu-3 and iGROV-1, but not African green monkey kidney-derived cell lines Vero E6, Vero/hSLAM, and Vero E6 overexpressing ACE-2 and TMPRSS2. In contrast, EG.5.1 was readily isolated from Vero E6 cells. These findings of replication-competent BA.2.86 provide further evidence of its altered infectivity characteristics, including higher infectivity of CaLu-3 cells, as observed for pseudoviruses in immortalised cell lines.4Qu P Xu K Faraone JN et al.Immune evasion, infectivity, and fusogenicity of SARS-CoV-2 omicron BA.2.86 and FLip variants.bioRxiv. 2023; (published online Sept 12.) (preprint).http://10.1101/2023.09.11.557206Google Scholar, 5Yang S Yu Y Jian F et al.Antigenicity and infectivity characterisation of SARS-CoV-2 BA.2.86.Lancet Infect Dis. 2023; 23: 457-459Summary Full Text Full Text PDF Scopus (0) Google Scholar Once isolated, BA.2.86 efficiently infected Vero E6 cells and induced a clear cytopathic effect (appendix p 5). Next, we evaluated BA.2.86 serum or plasma neutralisation for individuals who had an XBB.1.5 breakthrough infection (n=13; 12 received more than three vaccinations), BA.4 or BA.5 breakthrough infection (n=30; 23 received more than three vaccinations), or bivalent BA.4 or BA.5 mRNA vaccination (n=6, all received four vaccinations) 14–90 days before serum or plasma collection (appendix p 6). The median ages of the groups were 59·0 years (range 31–79), 59·5 years (20–76), and 53·5 years (28–73), respectively. The prevalence of comorbidities in the study group, diagnosed from 5 years before the first SARS-CoV-2 vaccination or Dec 27, 2020, did not differ significantly from more than 17 000 combined XBB.1.5 and BA.4 or BA.5 cases confirmed by whole genome sequencing in the same period. In people with XBB.1.5 or BA.4 or BA.5 breakthrough infections, the geometric mean neutralisation titres for BA.2.86 were substantially reduced compared with B.1, omicron BA.2, omicron BA.5, measuring 6–12-times lower (figure C; p<0·05 for all comparisons). Conversely, the geometric mean titres for BA.2.86 did not differ significantly from that of XBB.1 and EG.5.1, in any of the three cohorts (figure C; p>0·05 for all comparisons). In conclusion, this study addresses the paucity of BA.2.86 and EG.5.1 virus characterisation data on clinical isolates, which represent the pathogens circulating among individuals. Together with pseudovirus investigations, these live virus data suggest that, despite the highly different spike mutation constellation of BA.2.86 that alters monoclonal antibody specificities, the overall ability of polyclonal serum antibodies after an XBB.1.5 or BA.4 or BA.5 breakthrough infection to neutralise BA.2.86 is similar to that of circulating XBB recombinant strains.4Qu P Xu K Faraone JN et al.Immune evasion, infectivity, and fusogenicity of SARS-CoV-2 omicron BA.2.86 and FLip variants.bioRxiv. 2023; (published online Sept 12.) (preprint).http://10.1101/2023.09.11.557206Google Scholar, 5Yang S Yu Y Jian F et al.Antigenicity and infectivity characterisation of SARS-CoV-2 BA.2.86.Lancet Infect Dis. 2023; 23: 457-459Summary Full Text Full Text PDF Scopus (0) Google Scholar, 6Lasrado N Collier AY Hachmann N et al.Neutralization escape by SARS-CoV-2 omicron subvariant BA.2.86.bioRxiv. 2023; (published online Sept 5.) (preprint).https://doi.org/10.1101/2023.09.04.556272PubMed Google Scholar, 7Sheward DJ Yang Y Westerberg M et al.Sensitivity of BA.2.86 to prevailing neutralising antibody responses.Lancet Infect Dis. 2023; 23: 462-463Summary Full Text Full Text PDF Scopus (0) Google Scholar, 8An Y Zhou X Tao L et al.SARS-CoV-2 omicron BA.2.86: less neutralization evasion compared to XBB sub-variants.bioRxiv. 2023; (published online Sept 27.) (preprint).https://doi.org/10.1101/2023.09.26.559580Google Scholar This work was supported by co-funding from the EU's EU4Health programme (grant agreement number 101102733 DURABLE). Views and opinions expressed do not necessarily reflect those of the EU or European Health and Digital Executive Agency. Neither the EU nor the granting authority can be held responsible for them. The funder did not have any role in writing of the Correspondence or the decision to submit it for publication. LN serves as a council member of the European Society of Clinical Virology and is head of the Danish Society for Clinical Microbiology virology working group. PJ is the science officer of the European Society of Clinical Microbiology and Infectious Diseases Study Group in Public Health Microbiology, and a member of the European Society of Clinical Microbiology and Infectious Diseases Emerging Infections Task Force. All other authors declare no competing interests. Download .pdf (.58 MB) Help with pdf files Supplementary appendix