tetano
Editor, Senior Moderator
iScience
. 2026 Aug 11;29(8):117166.
doi: 10.1016/j.isci.2026.117166. eCollection 2026 Aug 21.
Michael S Piepenbrink 1 , Yao Ma 2 , Simran Panjwani 3 , Alexandra R Blake 1 , Allison M Bell 1 , James L Kizziah 3 , Sara H Mahmoud 2 , Gregory C Ippolito 2 , Nathan B Erdmann 1 , Paul A Goepfert 1 , Luis Martinez-Sobrido 2 , James J Kobie 1 , Mark R Walter 3
Affiliations
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution reduces the efficacy of prophylactic vaccines and monoclonal antibody (mAb) therapies. To evaluate potency and breadth, receptor binding domain (RBD)-targeting neutralizing mAbs were identified from patient B cells using an Omicron KP3.1.1 Spike (S) protein bait. MAbs exhibiting the greatest neutralization potency (1332D4 and 1332E5) and binding breadth (1324A10 and 1316C10) were evaluated in greater detail. Cryo-electron microscopy (Cryo-EM) studies revealed 1332D4 and 1332E5 target RBD residue segments 439-446 and 498-506 of KP3.1.1 S, respectively. 1332E5 is a knob498-506-targeting class-1/4 mAb that exhibits pan-Omicron specificity but does not bind or neutralize ancestral Wuhan-1. Further analysis suggests mAbs generically defined as class 1/4 mAbs may be separated into two classes. Class 1/4 mAbs, like 1332E5, and class 4/1 mAbs that make extensive interactions with the class-4 epitope and limited contacts with the class-1 knob498-596. Despite these differences, the specificity of both mAb classes can be altered by mutations in knob498-506.
Keywords: KP3.1.1; Omicron; SARS-CoV-2; broadly neutralizing antibody; cryoEM; structure; variant.
. 2026 Aug 11;29(8):117166.
doi: 10.1016/j.isci.2026.117166. eCollection 2026 Aug 21.
Emergence of neutralizing RBD antibodies following Omicron infection with limited activity against ancestral SARS-CoV-2
Michael S Piepenbrink 1 , Yao Ma 2 , Simran Panjwani 3 , Alexandra R Blake 1 , Allison M Bell 1 , James L Kizziah 3 , Sara H Mahmoud 2 , Gregory C Ippolito 2 , Nathan B Erdmann 1 , Paul A Goepfert 1 , Luis Martinez-Sobrido 2 , James J Kobie 1 , Mark R Walter 3
Affiliations
- PMID: 42621159
- PMCID: PMC13486884
- DOI: 10.1016/j.isci.2026.117166
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution reduces the efficacy of prophylactic vaccines and monoclonal antibody (mAb) therapies. To evaluate potency and breadth, receptor binding domain (RBD)-targeting neutralizing mAbs were identified from patient B cells using an Omicron KP3.1.1 Spike (S) protein bait. MAbs exhibiting the greatest neutralization potency (1332D4 and 1332E5) and binding breadth (1324A10 and 1316C10) were evaluated in greater detail. Cryo-electron microscopy (Cryo-EM) studies revealed 1332D4 and 1332E5 target RBD residue segments 439-446 and 498-506 of KP3.1.1 S, respectively. 1332E5 is a knob498-506-targeting class-1/4 mAb that exhibits pan-Omicron specificity but does not bind or neutralize ancestral Wuhan-1. Further analysis suggests mAbs generically defined as class 1/4 mAbs may be separated into two classes. Class 1/4 mAbs, like 1332E5, and class 4/1 mAbs that make extensive interactions with the class-4 epitope and limited contacts with the class-1 knob498-596. Despite these differences, the specificity of both mAb classes can be altered by mutations in knob498-506.
Keywords: KP3.1.1; Omicron; SARS-CoV-2; broadly neutralizing antibody; cryoEM; structure; variant.