SARS-CoV-2 BA.2.86 enters lung cells and evades neutralizing antibodies with high efficiency

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continually evolves, with new variants emerging.
• The BA.2.86 sublineage, a descendant of Omicron BA.2, possesses numerous spike protein mutations and has been detected globally.
• Understanding the biological characteristics of emerging SARS-CoV-2 variants is crucial for public health.

Purpose of the Study:

• To investigate the biological traits of the SARS-CoV-2 BA.2.86 variant, focusing on viral entry mechanisms.
• To assess the susceptibility of BA.2.86 to neutralization by therapeutic antibodies and vaccine-induced immunity.

Main Methods:

• Utilized pseudotyped particles to evaluate viral entry into Calu-3 lung cells.
• Confirmed findings with authentic BA.2.86 virus.
• Assessed neutralization by antibodies from non-adapted and XBB.1.5-adapted vaccines, as well as therapeutic antibodies.

Main Results:

• BA.2.86 demonstrated efficient entry into lung cells, dependent on serine proteases but not cysteine proteases.
• Authentic BA.2.86 showed robust lung cell infection but low specific infectivity.
• BA.2.86 exhibited high resistance to therapeutic antibodies and antibodies from non-adapted vaccines.
• Antibodies from XBB.1.5-adapted vaccines effectively neutralized BA.2.86 and EG.5.1.

Conclusions:

• BA.2.86 has regained efficient lung cell entry, a characteristic of early SARS-CoV-2 lineages.
• The variant demonstrates significant immune evasion capabilities against existing antibody-based interventions.
• Low specific infectivity might mitigate the transmissibility of BA.2.86 despite its other concerning traits.