Human monoclonal antibodies isolated after seasonal vaccination broadly neutralize antigenically drifted influenza B viruses.
Summary
Post-2019 influenza B strains escape several prior bnAbs, but two new human bnAbs (CAV-CF22, CAV-CH76) isolated after quadrivalent vaccination broadly neutralize and protect against contemporary Victoria and Yamagata lineages. Structural analyses show HCDR3-mediated receptor-binding-site mimicry that is resilient to K136E drift, informing drift-resistant vaccine and antibody design.
Key Findings
- Post-2019 IBV strains escaped several previously identified head-directed bnAbs.
- Two new human bnAbs (CAV-CF22, CAV-CH76) broadly neutralized Victoria and Yamagata lineages and conferred in vivo protection.
- Fixation of K136E in Victoria HA disrupted many prior antibody epitopes.
- High-resolution structures showed HCDR3 insertion into the RBS to mimic sialic acid, explaining breadth and drift resilience.
Clinical Implications
Guides immunogen design toward conserved RBS features and supports development of bnAb therapeutics robust to K136E drift; suggests surveillance of K136E as a marker of vaccine escape. Translation could reduce seasonal vaccine mismatch for influenza B.
Why It Matters
This paper identifies drift-resilient neutralizing solutions to a rapidly evolving respiratory virus, combining human mAb discovery, in vivo protection, and structural mechanisms. It directly informs next-generation influenza B vaccines and therapeutic antibodies.
Limitations
- Preclinical nature without human efficacy data for the bnAbs.
- Limited number of bnAbs characterized; future drift patterns beyond K136E may still affect breadth.
Future Directions
Design and test RBS-mimicking immunogens and evaluate these bnAbs and vaccine concepts in clinical studies; monitor HA-136 variants for impact on antibody breadth.
Study Information
- Study Type
- Basic/mechanistic study
- Research Domain
- Pathophysiology
- Evidence Level
- V - Preclinical mechanistic and structural biology evidence with in vivo animal protection
- Study Design
- OTHER