Potent neutralization by a RBD antibody with broad specificity for SARS-CoV-2 JN.1 and other variants

Area of Science:

• Virology
• Immunology
• Drug Discovery

Background:

• SARS-CoV-2 evolution and antigenic diversification necessitate new therapeutic strategies.
• Current vaccines offer protection but are challenged by viral mutations.
• Prophylactic and treatment interventions are needed that are resistant to viral evolution.

Purpose of the Study:

• To develop a broadly neutralizing human monoclonal antibody against SARS-CoV-2 variants.
• To identify an antibody targeting conserved regions of the Spike protein's Receptor Binding Domain (RBD).
• To evaluate the therapeutic potential of a novel antibody in preclinical models.

Main Methods:

• Developed a recombinant human monoclonal antibody (hmAb) 1301B7 from an Omicron-infected convalescent individual.
• Utilized a differential staining strategy with SARS-CoV-2 RBD-ACE2 fusion and Omicron RBD proteins.
• Assessed neutralization breadth against various SARS-CoV-2 strains and SARS-CoV.
• Determined antibody binding epitope and heavy chain usage (VH1-69).
• Evaluated in vivo efficacy in mouse models challenged with Omicron variants.

Main Results:

• hmAb 1301B7 potently neutralized a wide spectrum of SARS-CoV-2 variants, including Wuhan-1, Omicron JN.1, and SARS-CoV.
• The antibody targets conserved residues (Y501, H505) within the RBD, exclusively via its VH1-69 heavy chain.
• 1301B7 significantly reduced viral burden in respiratory tracts and protected mice against Omicron XBB1.5 and JN.1 challenge.

Conclusions:

• hmAb 1301B7 demonstrates broad neutralizing activity against diverse SARS-CoV-2 variants.
• The antibody's conserved epitope targeting offers potential for durable therapeutic and prophylactic applications.
• 1301B7 may guide the development of universal SARS-CoV-2 vaccines and therapeutics targeting the RBD.