Broadly Sarbecovirus-Neutralizing Antibodies Induced by Ancestral SARS-CoV-2 Infection

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• The COVID-19 pandemic caused by SARS-CoV-2 highlights the threat of emerging sarbecoviruses.
• Neutralizing antibodies targeting the spike (S) glycoprotein's receptor-binding domain (RBD) are key for viral control and vaccine development.
• Understanding cross-reactive immune responses from ancestral SARS-CoV-2 infection is crucial.

Purpose of the Study:

• To investigate cross-reactive humoral responses induced by ancestral SARS-CoV-2 infection.
• To identify broadly neutralizing monoclonal antibodies (mAbs) against SARS-CoV-2 and related sarbecoviruses.

Main Methods:

• Isolation of 105 S-specific mAbs from individuals recovered from SARS-CoV-2 infection.
• Assessment of cross-reactivity against SARS-CoV-1 and neutralization of viral variants.
• Cryo-electron microscopy to determine antibody-epitope interactions.

Main Results:

• 30 out of 105 mAbs cross-recognized SARS-CoV-1, with 25 targeting the RBD.
• 12 mAbs demonstrated cross-neutralizing activity against both SARS-CoV-1 and SARS-CoV-2 variants.
• mAb 12C2 potently neutralized SARS-CoV-1 and SARS-CoV-2 variants by inhibiting membrane fusion and destabilizing the S trimer.

Conclusions:

• Ancestral SARS-CoV-2 infection can induce potent cross-neutralizing antibody responses.
• The identified mAbs, like 12C2, provide a basis for designing broadly protective antibodies and vaccines against sarbecoviruses.
• Understanding antibody binding sites on the RBD is vital for next-generation vaccine strategies.