| Title | In vivo evolution of antibody CR3022 expands cross-neutralization of SARS-CoV-2 variants and informs pan-sarbecovirus immunity. |
| Publication Type | Journal Article |
| Year of Publication | 2026 |
| Authors | Fu Y, Feng Z, Erickson SA, Halfmann PJ, Li L, Chervin JC, Troxell CA, Sun J, Yasuhara A, Changrob S, Huang M, Zheng N-Y, Yuan M, Kawaoka Y, Wilson IA, Wilson PC |
| Journal | Cell Rep |
| Volume | 45 |
| Issue | 4 |
| Pagination | 117137 |
| Date Published | 2026 Mar 21 |
| ISSN | 2211-1247 |
| Abstract | The epitope that monoclonal CR3022 binds to represents a promising target for broad protection against a wide range of human and zoonotic coronaviruses. We develop a powerful model to evaluate antibody affinity maturation in vivo using immunoglobulin (Ig)-humanized mice that express the predicted germline heavy chain of antibody CR3022. Severe acute respiratory syndrome coronavirus (SARS-CoV)/SARS-CoV-2 sequential immunization leads to the convergent evolution of the germline CR3022 through somatic hypermutation (SHM), resembling the affinity-matured CR3022 from a human but now also adapting to key variants and divergent sarbecoviruses. While simple prime-boost strategies drive CR3022-epitope targeting, an intensive vaccination protocol elicits dominant responses to other epitopes. X-ray crystal structures reveal that SARS-CoV-2-neutralizing CR3022-like antibodies exhibit enhanced affinity by increasing polar and electrostatic interactions. Overall, these findings show that CR3022-like clones can be readily adapted through SHM to increase breadth and potency to sarbecoviruses by relatively minor shifts in affinity with appropriate vaccination strategies. |
| DOI | 10.1016/j.celrep.2026.117137 |
| Custom 1 | |
| Alternate Journal | Cell Rep |
| PubMed ID | 41865371 |