Delta-Omicron recombinant escapes therapeutic antibody neutralization

Area of Science:

• Virology
• Immunology
• Public Health

Background:

• Recombinant viruses can emerge with novel characteristics, posing risks to public health.
• The selective advantages and clinical implications of SARS-CoV-2 recombination are not fully understood.
• Monoclonal antibodies are crucial therapeutics for managing SARS-CoV-2 infections.

Purpose of the Study:

• To identify and characterize SARS-CoV-2 recombinants.
• To investigate the functional impact of recombination on viral resistance to therapeutic monoclonal antibodies.
• To understand the role of recombination in viral immune escape.

Main Methods:

• Identification of a SARS-CoV-2 Delta-Omicron recombinant in an immunosuppressed patient.
• Genomic sequencing to pinpoint the recombination breakpoint.
• In vitro neutralization assays to assess viral sensitivity to Sotrovimab.

Main Results:

• A novel Delta-Omicron (AY.45-BA.1) recombinant SARS-CoV-2 was identified.
• The recombination breakpoint was located in the spike N-terminal domain, near the Sotrovimab binding site.
• The recombinant exhibited high resistance to Sotrovimab neutralization, unlike its parental lineages.

Conclusions:

• This is the first report of a SARS-CoV-2 recombinant exhibiting functional resistance to monoclonal antibody treatment.
• Viral recombination can serve as a mechanism for immune escape and treatment resistance.
• The emergence of such recombinants necessitates ongoing surveillance and characterization.