ABSTRACT
Omicron BA.2.86 subvariant differs from Omicron BA.2 as well as recently circulating variants by over 30 mutations in the spike protein alone. Here we report on the first isolation of the live BA.2.86 subvariant from a diagnostic swab collected in South Africa which we tested for escape from neutralizing antibodies and viral replication properties in cell culture. BA.2.86 did not have significantly more escape than Omicron XBB.1.5 from neutralizing immunity elicited by infection of Omicron subvariants ranging from BA.1 to XBB, either by infection alone or as breakthrough infection in vaccinated individuals. Neutralization escape was present relative to earlier strains: BA.2.86 showed extensive escape both relative to ancestral virus in sera from pre-Omicron vaccinated individuals and relative to Omicron BA.1 in sera from Omicron BA.1 infected individuals. We did not observe substantial differences in viral properties in cell culture relative to XBB.1.5. Both BA.2.86 and XBB.1.5 produced infection foci of similar size, had similar cytopathic effect (both lower than ancestral SARS-CoV-2), and had similar replication dynamics. We also investigated the relationship of BA.2.86 to BA.2 sequences and found that the closest were BA.2 samples from Southern Africa circulating in early 2022. These observations suggest that BA.2.86 is more closely related to sequences from Southern Africa than other regions and so may have evolved there, and that evolution led to escape from neutralizing antibodies similar in scale to recently circulating strains of SARS-CoV-2.
Subject(s)
Breakthrough PainABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in southern Africa has been characterised by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, whilst the second and third waves were driven by the Beta and Delta variants respectively. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng Province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, predicted to influence antibody neutralization and spike function4. Here, we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity.
Subject(s)
Severe Acute Respiratory SyndromeABSTRACT
Global genomic surveillance of SARS-CoV-2 has identified variants associated with increased transmissibility, neutralization resistance and disease severity. Here we report the emergence of the PANGO lineage C.1.2, detected at low prevalence in South Africa and eleven other countries. The emergence of C.1.2, associated with a high substitution rate, includes changes within the spike protein that have been associated with increased transmissibility or reduced neutralization sensitivity in SARS-CoV-2 VOC/VOIs. Like Beta and Delta, C.1.2 shows significantly reduced neutralization sensitivity to plasma from vaccinees and individuals infected with the ancestral D614G virus. In contrast, convalescent donors infected with either Beta or Delta showed high plasma neutralization against C.1.2. These functional data suggest that vaccine efficacy against C.1.2 will be equivalent to Beta and Delta, and that prior infection with either Beta or Delta will likely offer protection against C.1.2.