Bispecific antibodies targeting the N-terminal and receptor binding domains potently neutralize SARS-CoV-2 variants of concern.
Total: 79.0Innovation: 9Impact: 8Rigor: 7Citation: 8
Summary
Engineering NTD–RBD bispecific antibodies (CoV2-biRNs) yielded potent and breadth-resilient neutralization across Omicron variants (XBB.1.5, BA.2.86, JN.1), outperforming monotherapy/cocktail parents. Prophylactic bsAb delivery reduced XBB.1.5 lung viral load in K18-hACE2 mice.
Key Findings
- C1596 NTD mAb recognizes a distinct epitope outside the NTD site i supersite, enabling broad binding.
- NTD–RBD bispecifics (CoV2-biRN5/7) retained potent neutralization against Omicron variants XBB.1.5, BA.2.86, and JN.1, outperforming parental mAbs/cocktails.
- Prophylactic CoV2-biRN5 reduced lung viral load in K18-hACE2 mice challenged with XBB.1.5.
Clinical Implications
Supports development of bispecific antibody therapeutics resilient to VOC escape; may inform next-generation COVID-19 prophylaxis or treatment strategies.
Why It Matters
Demonstrates a generalizable antibody architecture that maintains potency against highly evasive Omicron lineages, with structural rationale and in vivo validation.
Limitations
- Lack of human clinical efficacy or safety data for bsAbs
- Manufacturing complexity and potential immunogenicity of bispecific constructs not addressed
Future Directions
Advance bsAbs to phase 1 human trials, assess durability against emerging variants, and compare prophylactic vs. therapeutic use.
Study Information
- Study Type
- Basic/Mechanistic
- Research Domain
- Treatment
- Evidence Level
- III - Preclinical structural, in vitro neutralization, and mouse efficacy data
- Study Design
- OTHER