CAO Antibody

Introduction to CAO Antibody

The term "CAO Antibody" refers to a class of monoclonal antibodies (mAbs) discovered and characterized by researchers affiliated with the Yunlong Cao Lab at Peking University, focusing on humoral immunity and antiviral therapeutics . These antibodies are engineered to target highly conserved epitopes of viral pathogens, particularly SARS-CoV-2 variants, with an emphasis on broad-spectrum neutralization and evasion resistance . Notably, CAO Antibodies such as CR9 have demonstrated potent activity against Omicron subvariants, including BA.1, BA.2, BA.4, and BA.5, by binding to critical regions of the viral spike protein’s receptor-binding domain (RBD) .

Key milestones:

• CR9 Identification: Isolated from a convalescent donor’s B-cell library, CR9 was selected for its high affinity to Omicron RBD, with dissociation constants (Kd) ranging from $4.993 \times 10^{-14}$ M (BA.1) to $5.689 \times 10^{-13}$ M (BA.5) .

• Phage Display Screening: A Fab phage display library ($1 \times 10^8$ clones) was screened against SARS-CoV-2 spike proteins, leading to CR9’s isolation and conversion into a full-length IgG1 antibody .

Epitope Mapping:

CR9 binds to a conserved RBD epitope involving residues critical for ACE2 receptor interaction. Cryo-EM studies revealed direct competition with ACE2, blocking viral entry .

Neutralization Mechanisms:

• ACE2 Blockade: CR9 sterically hinders ACE2 binding, reducing viral attachment .

• Conformational Locking: Induces structural rigidity in the RBD, limiting viral membrane fusion .

Neutralization Potency:

CR9 neutralizes Omicron subvariants with half-maximal inhibitory concentrations (IC$_{50}$) as follows:

Source: In vitro pseudovirus assays .

Animal Models:

• Prophylactic Use: Reduced lung viral titers by >99% in hACE2-transgenic mice challenged with BA.2.12.1 .

• Therapeutic Use: Achieved log$_{10}$ 1.44 reduction in viral load post-infection .

Clinical and Research Applications

• Therapeutic Potential: CR9 is under evaluation as an adjunct therapy for Omicron infections due to its resistance to immune evasion .

• Vaccine Design: Epitope characterization informs next-generation vaccines targeting conserved RBD regions .

• Diagnostic Tools: High-affinity binding enables ultrasensitive detection of SARS-CoV-2 antigens .

Research Significance and Challenges

• Immune Evasion: CR9 retains activity against BA.2.86 but shows reduced efficacy against JN.1 due to F486P mutation .

• Antibody Durability: Longitudinal studies indicate waning neutralizing titers over time, necessitating booster strategies .

• Broad-Spectrum Limitations: While effective against Omicron, CAO Antibodies may require iterative updates for emerging variants .