A structure-function analysis shows SARS-CoV-2 BA.2.86 balances antibody escape and ACE2 affinity

Area of Science:

• Virology
• Immunology
• Structural Biology

Background:

• BA.2.86 is a novel sublineage of SARS-CoV-2 Omicron with extensive spike gene mutations.
• It is antigenically distinct from previously dominant XBB variants.
• Concerns exist regarding its potential for immune evasion and causing new infection waves.

Purpose of the Study:

• To assess the immune-evasive properties of BA.2.86 against antibody responses.
• To compare BA.2.86's immune evasion with that of XBB.1.5.
• To investigate the structural basis for BA.2.86's interaction with ACE2 and its potential impact on transmissibility.

Main Methods:

• Analysis of BA.2.86's antibody evasion using sera from vaccinated or naturally infected individuals.
• Antigenic landscape mapping of BA.2.86 relative to other SARS-CoV-2 variants.
• Evaluation of BA.2.86's escape from potent monoclonal antibodies.
• Structural analysis of BA.2.86's binding affinity to ACE2.

Main Results:

• BA.2.86 demonstrated marginally less immune evasion compared to XBB.1.5.
• The study provides a structural explanation for BA.2.86's increased affinity for ACE2.
• BA.2.86 exhibits distinct antigenic properties within the Omicron variant landscape.

Conclusions:

• BA.2.86 possesses a notable degree of immune evasion but is less evasive than XBB.1.5.
• Increased ACE2 binding affinity suggests potentially higher transmissibility for BA.2.86.
• Further monitoring of BA.2.86 is warranted due to its unique mutational profile and potential for spread.