Potent Omicron-neutralizing antibodies isolated from a patient vaccinated 6 months before Omicron emergence

Area of Science:

• Immunology
• Virology
• Structural Biology

Background:

• Therapeutic antibodies are crucial for combating coronavirus infections.
• Many early antibodies are ineffective against new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains, especially Omicron.
• This necessitates the development of broadly neutralizing antibodies.

Purpose of the Study:

• To identify and characterize novel vaccinee-derived antibodies with broad-spectrum neutralization activity against SARS-CoV-2 variants.
• To understand the structural and biochemical basis for the broad efficacy of these antibodies.
• To evaluate the protective potential of these antibodies in a preclinical model.

Main Methods:

• Screening of vaccinee-derived antibody panels for neutralization activity against SARS-CoV-2 variants.
• Structural and biochemical analyses of lead antibodies, including binding footprint and avidity studies.
• In vivo efficacy testing in the K18 mouse model of SARS-CoV-2 infection.

Main Results:

• Identification of a panel of vaccinee-derived antibodies with broad-spectrum neutralization capabilities.
• Structural and biochemical characterization revealed complementary binding footprints and varying avidity requirements to overcome variant mutations.
• Three selected antibodies demonstrated protective efficacy against BA.1 and BA.2 infections in the K18 mouse model.

Conclusions:

• Vaccinee-derived antibodies can possess broad-spectrum activity against SARS-CoV-2 variants.
• Understanding antibody footprints and avidity is key to overcoming variant-associated mutations.
• These findings provide a foundation for developing next-generation, broadly protective coronavirus therapeutics.