tetano
Editor, Senior Moderator
Cell Rep
. 2026 Mar 21;45(4):117137.
doi: 10.1016/j.celrep.2026.117137. Online ahead of print.
In vivo evolution of antibody CR3022 expands cross-neutralization of SARS-CoV-2 variants and informs pan-sarbecovirus immunity
Yanbin Fu[SUP] 1 [/SUP], Ziqi Feng[SUP] 2 [/SUP], Steven A Erickson[SUP] 3 [/SUP], Peter J Halfmann[SUP] 4 [/SUP], Lei Li[SUP] 5 [/SUP], Jordan C Chervin[SUP] 1 [/SUP], Chloe A Troxell[SUP] 1 [/SUP], Jiayi Sun[SUP] 1 [/SUP], Atsuhiro Yasuhara[SUP] 1 [/SUP], Siriruk Changrob[SUP] 1 [/SUP], Min Huang[SUP] 1 [/SUP], Nai-Ying Zheng[SUP] 1 [/SUP], Meng Yuan[SUP] 2 [/SUP], Yoshihiro Kawaoka[SUP] 4 [/SUP], Ian A Wilson[SUP] 2 [/SUP], Patrick C Wilson[SUP] 6 [/SUP]
Affiliations
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.
Keywords: B cell responses; CP: immunology; CP: microbiology; CR3022 antibody; SARS-CoV-2 neutralizations; antibody evolution; somatic hypermutation.
. 2026 Mar 21;45(4):117137.
doi: 10.1016/j.celrep.2026.117137. Online ahead of print.
In vivo evolution of antibody CR3022 expands cross-neutralization of SARS-CoV-2 variants and informs pan-sarbecovirus immunity
Yanbin Fu[SUP] 1 [/SUP], Ziqi Feng[SUP] 2 [/SUP], Steven A Erickson[SUP] 3 [/SUP], Peter J Halfmann[SUP] 4 [/SUP], Lei Li[SUP] 5 [/SUP], Jordan C Chervin[SUP] 1 [/SUP], Chloe A Troxell[SUP] 1 [/SUP], Jiayi Sun[SUP] 1 [/SUP], Atsuhiro Yasuhara[SUP] 1 [/SUP], Siriruk Changrob[SUP] 1 [/SUP], Min Huang[SUP] 1 [/SUP], Nai-Ying Zheng[SUP] 1 [/SUP], Meng Yuan[SUP] 2 [/SUP], Yoshihiro Kawaoka[SUP] 4 [/SUP], Ian A Wilson[SUP] 2 [/SUP], Patrick C Wilson[SUP] 6 [/SUP]
Affiliations
- PMID: 41865371
- DOI: 10.1016/j.celrep.2026.117137
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.
Keywords: B cell responses; CP: immunology; CP: microbiology; CR3022 antibody; SARS-CoV-2 neutralizations; antibody evolution; somatic hypermutation.