De novo design of CR2 binder as vaccine scaffold
Liu, Y.-T.; Yin, Y.-N.; Xu, H.-Q.; Du, W.-T.; Xie, C.; Wu, P.-H.; Zhou, H.; Cheng, B.-Z.; Bu, G.-L.; Feng, G.-K.; Zhong, Q.; Liu, Z.; Zeng, M.-S.; Sun, C.
Show abstract
Efficient B cell activation during vaccine-induced humoral immunity relies on both B cell receptor (BCR) antigen recognition and synergistic signaling from co-receptors. Complement receptor 2 (CR2), the primary BCR co-receptor on B cells, lowers the activation threshold and amplifies downstream kinase signaling by orders of magnitude when engaged by complement fragment C3d decorated antigens. Targeting CR2 therefore represents a rational vaccine enhancement strategy, yet native C3d suffers from low affinity, poor stability, and manufacturing challenges. Here, we report the de novo design of a highly stable, high-affinity CR2 binder using deep learning driving protein design methods. Biophysical characterization, high-resolution cryoEM structural determination, and functional assays in vitro and in vivo confirm that the designed binder matches computational design models and specifically engages CR2 to boost B cell activation. When fused to antigen as a vaccine scaffold, the trimeric CR2 binder elicits robust humoral immune responses comparable to nanoparticle vaccines, while retaining the simplicity of single-chain protein production. Our work establishes a modular CR2 targeting vaccine scaffold platform with broad translational potential for next-generation protein vaccines.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates 95%
- Multivalency transforms SARS-CoV-2 antibodies into broad and ultrapotent neutralizers 95%
- Engineered Immunogens to Elicit Antibodies Against Conserved Coronavirus Epitopes 94%
Similar papers in this journal
- Structural insights into VRC01-class bnAb precursors with diverse light chains elicited in the IAVI G001 human vaccine trial 96%
- An engineered closed-shell, two-component, 480-subunit nucleocapsid 94%
- Deep Mining of the Human Antibody Repertoire Identifies Frequent and Immunogenetically Diverse CDRH3 Topologies Targetable by Vaccination 94%
Similar papers in this journal
Similar papers in this journal
- SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8 T cells 91%
- Distinct baseline immune characteristics associated with responses to conjugated and unconjugated pneumococcal polysaccharide vaccines in older adults 91%
- High-Throughput and High-Dimensional Single Cell Analysis of Antigen-Specific CD8+ T cells 90%
Similar papers in this journal
- Structural basis for antibody cross-neutralization of dengue and Zika viruses 92%
- TH5487 specifically targets NLRP3 in FCAS patients resistant to MCC950 92%
- Combinatorial multimer staining and spectral flow cytometry facilitate quantification and characterization of polysaccharide-specific B cell immunity 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.