ADG2 Antibody
Description
Mechanism of Action
ADG2 targets a conserved epitope overlapping the receptor-binding site (RBD) of the SARS-CoV-2 spike protein. Key features include:
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Epitope Conservation: Binds residues shared across clade 1 sarbecoviruses, including G496, Y489, F486, and Y449 .
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Structural Uniqueness: Employs a divergent angle of approach compared to other VH3–53-class antibodies, enabling broad recognition .
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ACE2 Competition: Directly blocks ACE2 receptor engagement while engaging the CR3022 site for added breadth .
Neutralization Potency
ADG2 neutralizes coronaviruses with sub-nanomolar IC50 values:
| Virus/Strain | IC50 (ng/mL) | Source |
|---|---|---|
| SARS-CoV-2 (ancestral) | ~1 | |
| SARS-CoV | 4–8 | |
| WIV-1 | 6 | |
| SHC014 | 8 | |
| Omicron (B.1.1.529) | 20–500* |
*Reduced potency against Omicron due to extensive RBD mutations .
In Vivo Protection
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SARS-CoV-2 Challenge: Complete protection against lung pathology and viral replication in mice at 10 mg/kg .
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SARS-CoV Challenge: 100% survival and reduced lung inflammation in murine models .
Fc-Mediated Effector Functions
ADG2 triggers polyfunctional immune responses superior to clinical benchmarks :
| Function | ADG2 Performance vs. S309/REGN10987 |
|---|---|
| NK Cell Activation | Superior |
| Complement Deposition | Equivalent/Enhanced |
| Phagocytosis | Equivalent |
Resistance Profile
ADG2 binds all major SARS-CoV-2 variants with minimal potency loss :
| Variant | Binding Affinity vs. Wild-Type |
|---|---|
| Alpha (B.1.1.7) | ≥98% |
| Beta (B.1.351) | ≥95% |
| Gamma (P.1) | ≥90% |
| Delta (B.1.617.2) | ≥92% |
| Omicron (B.1.1.529) | ≥85% |
No mutations at ADG2 contact residues were observed in >152,000 SARS-CoV-2 genomes (GISAID, 2020) .
Clinical Development (ADG20)
ADG20, the half-life-engineered derivative, exhibits:
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Extended Half-Life: ~100 days post-300 mg intramuscular dose .
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Phase 1 Safety: No drug-related adverse events in healthy volunteers .
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Phase 2/3 Trials: Ongoing for COVID-19 treatment (STAMP trial) and prophylaxis, including pediatric studies .
Biophysical Advantages
Product Specs
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Target Background
- May contribute to ADP-glucose synthesis PMID: 18614708
Q&A
FAQs for ADG2 Antibody Research
Target audience: Academic researchers in virology, immunology, and therapeutic antibody development
Advanced Research Questions
What methodologies identified ADG2’s resistance profile against emerging variants?
Methodology:
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Deep mutational scanning: Tested binding against 36 SARS-CoV-2 RBD variants from GISAID (e.g., N501Y, K417N). ADG2 maintained ≥50% binding efficiency across all variants, unlike REGN10933 (loss in 8/36) .
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In vitro escape studies: Serial passaging of SARS-CoV-2 in ADG2 pressure identified rare mutations (e.g., G504D) with fitness costs .
Resistance analysis:
| Mutation | Fold Change in IC₅₀ | Prevalence in GISAID (2020–2021) |
|---|---|---|
| E484K | 1.2x | 18% |
| N501Y | 1.1x | 22% |
| G504D | 32x | <0.01% |
| Source: |
How were preclinical efficacy models designed to evaluate ADG2’s therapeutic potential?
Methodology:
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Prophylactic vs. therapeutic models: Administered ADG2 (5–25 mg/kg) to hACE2 transgenic mice 24h pre- or post-SARS-CoV-2 challenge. Outcomes:
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Cross-species validation: Tested in Syrian hamsters and ferrets for mucosal protection .
Model comparison:
| Model | Dose (mg/kg) | Protection Efficacy | Key Endpoint |
|---|---|---|---|
| Murine SARS | 10 | 100% survival | Lung histopathology |
| Hamster COVID | 25 | 3.8-log reduction | Viral titer (nasal turbinate) |
| Source: |
What biophysical assays validated ADG2’s manufacturability and stability?
Methodology:
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Thermal shift assays: Melting temperature (Tm) = 72°C, indicating high stability .
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Aggregation propensity: <5% high-molecular-weight species after 4 weeks at 40°C .
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Expression yield: Achieved 3.2 g/L in CHO cells, comparable to clinical-stage mAbs .
Biophysical profile:
| Parameter | Result | Industry Benchmark |
|---|---|---|
| Solubility (mg/mL) | 180 | >100 |
| Serum half-life (mice) | 21 days | 14–28 days |
| FcγRIIIa binding (nM) | 8.4 | <10 |
| Source: |
How does ADG2’s Fc-mediated effector function compare to other SARS-CoV-2 mAbs?
Methodology:
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ADCC/ADCP assays: Measured NK cell activation (CD107a+) and phagocytosis by THP-1 monocytes. ADG2 outperformed S309 in NK activation (68% vs. 42%) .
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Complement deposition: C3d levels were 2.3x higher than REGN10987 .
Functional comparison:
