A master of immune escape but not taking on yet

In a recent study posted to the medRxiv preprint* server, researchers isolate BA.2.86, a brand new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant, and assess its immune-evading and replication properties.

Study: Evolution and neutralization escape of the SARS-CoV-2 BA.2.86 subvariant. Image Credit: Starshaker / Shutterstock.com

*Essential notice: medRxiv publishes preliminary scientific reports that usually are not peer-reviewed and, subsequently, shouldn’t be thought to be conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

BA.2.86 is a derivative of the Omicron BA.2 subvariant. This novel SARS-CoV-2 variant shares the spike (S) protein substitution S939F and synonymous mutation C26681T with BA.2 genomes collected in South Africa in early 2022. Nonetheless, the C9866T mutation, typically present in most BA.2 sequences sampled from outside South Africa, is absent in BA.2.86. 

BA.2.86 accommodates 30 additional mutations in its S protein relative to BA.2 and essentially the most recently circulating SARS-CoV-2 XBB.1.5 variant. The emergence of Omicron BA.2.86 is concerning, as lots of these latest mutations allow for the escape of neutralizing antibodies (nAbs) induced by prior infection and vaccination.

Global genomic surveillance systems initially detected Omicron BA.2.86 in July 2023. Nonetheless, it stays unclear when BA.2.86 initially emerged and commenced spreading, as surveillance efforts have significantly reduced for the reason that start of the coronavirus disease 2019 (COVID-19) pandemic.

In regards to the study

Researchers extracted viral ribonucleic acid (RNA) from the BA.2.86 swab sample to arrange whole genome sequencing (WGS) libraries, which were quantified using the Qubit double-stranded DNA (dsDNA) high-sensitivity assay. After fragment size evaluation, libraries were pooled, normalized, and loaded onto the Illumina NextSeq 1000/2000 instrument to generate genome sequences for WGS evaluation.

Nextclade and Pangolin versions 2.14.1 and 4.3, respectively, were used for clade and lineage assignments. Nextclade was also used to visualise the sequences and detect frameshift mutations. Oxford Nanopore sequencing was also performed.

The neutralization of BA.2.86 was compared with that of XBB.1.5 using sera from vaccinated individuals, those with a breakthrough infection from an Omicron subvariant, and people infected with only Omicron subvariants. The researchers then determined whether BA.2.86 evolved to flee neutralizing immunity relative to earlier SARS-CoV-2 strains. 

To measure the cellular spread of Omicron BA.2.86, the variety of cells infected by a single cell to form an infected cell cluster was determined using a live virus focus-forming assay in Vero-TMPRSS cells. The cytopathic effect (CPE) and viral replication were also determined.

Phylogenetic evaluation of the BA.2 sequences collected between November 2021 and June 2022 was also performed using data deposited within the Global Initiative on Sharing All Influenza Data (GISAID) database, aligned pairwise against Wuhan-Hu-1. The IQ-tree 2 was used to construct a phylogenetic tree.

Study findings

As in comparison with XBB.1.5, BA.2.86 didn’t exhibit significant immune evasion capabilities. Nonetheless, the immune escape of BA.2.86 relative to the ancestral SARS-CoV-2 strain was five-fold greater than BA.1. Moreover, BA.2.86 exhibited 14-fold greater escape capabilities when tested against the sera of individuals infected with BA.1; nonetheless, XBB.1.5 exhibited a comparable 12-fold escape.

At 20 hours post-infection, XBB.1.5 and BA.2.86 generated infection foci that were 4.5- and five-fold smaller than those of the SARS-CoV-2 ancestral strain. By 72 hours, reduced CPE was observed in BA.2.86- and XBB.1.5-infected cells as in comparison with ancestral SARS-CoV-2 infected cells. 

BA.2.86 appears to have descended from SARS-CoV-2 Omicron sublineages BA.1/BA.2, which were the dominant circulating strains in early 2021. Despite this extensive evolutionary trajectory, BA.2.86 didn’t widely spread on the population level, which can indicate that BA.2.86 originally evolved in an immunosuppressed individual.

Molecular clock evaluation with TreeTime indicated that BA.2.86 likely began to spread from May 2023 onward. Because the time of this study’s publication, the researchers have deposited sequences of isolated Omicron BA.2.86 and its associated metadata within the GISAID.

Conclusions

Although Omicron BA.2.86 evolved to flee nAb-mediated immunity, convalescent plasma recognized it to the same extent as XBB.1.5. These observations provide vital insights into the comparatively slow spread of BA.2.86 relative to Omicron BA.1/BA.2.

Thus, although BA.2.86 might cause latest infections on the population level now, it doesn’t differ significantly from other SARS-CoV-2 variants currently circulating worldwide.

BA.2.86 is more closely related to sequences from Southern Africa than other regions and so can have evolved there, and that evolution led to flee from neutralizing antibodies similar in scale to recently circulating strains of SARS-CoV-2.”

*Essential notice: medRxiv publishes preliminary scientific reports that usually are not peer-reviewed and, subsequently, shouldn’t be thought to be conclusive, guide clinical practice/health-related behavior, or treated as established information.