SARS-CoV-2 Omicron sublineages exhibit distinct antibody escape patterns

Area of Science:

• Virology
• Immunology
• Infectious Diseases

Background:

• Neutralizing antibodies are crucial for COVID-19 prevention and treatment.
• Viral evolution, particularly Omicron sublineages (BA.2.12.1, BA.4/5), poses challenges to existing antibody efficacy.
• Understanding antibody escape is vital for effective COVID-19 countermeasures.

Purpose of the Study:

• To assess polyclonal serum activity against emerging Omicron sublineages.
• To delineate antigenic differences and antibody escape patterns among Omicron variants.
• To identify potent neutralizing antibodies effective against SARS-CoV-2 variants.

Main Methods:

• Evaluated serum activity from 50 convalescent or vaccinated individuals.
• Tested antibody neutralization against Omicron sublineages BA.1, BA.1.1, BA.2, BA.2.12.1, and BA.4/5.
• Assessed sensitivity using an extended panel of 163 antibodies.

Main Results:

• Observed reduced susceptibility of BA.4/5 to vaccinee sera.
• Identified distinct antigenic differences and escape patterns among Omicron sublineages.
• Found most clinical-stage monoclonal antibodies ineffective against Omicron sublineages, but identified promising pan-neutralizing antibodies.

Conclusions:

• Antigenic distance and resistance likely drive BA.4/5 expansion.
• Emerging Omicron sublineages exhibit significant antibody escape.
• The study provides insights for developing strategies against SARS-CoV-2 variants.