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TitleEmergence of neutralizing RBD antibodies following Omicron infection with limited activity against ancestral SARS-CoV-2.
Journal, issue, pagesiScience, Vol. 29, Issue 8, Page 117166, Year 2026
Publish dateAug 21, 2026
AuthorsMichael S Piepenbrink / Yao Ma / Simran Panjwani / Alexandra R Blake / Allison M Bell / James L Kizziah / Sara H Mahmoud / Gregory C Ippolito / Nathan B Erdmann / Paul A Goepfert / Luis Martinez-Sobrido / James J Kobie / Mark R Walter /
PubMed AbstractSevere 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 ...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 knob-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 knob. Despite these differences, the specificity of both mAb classes can be altered by mutations in knob.
External linksiScience / PubMed:42621159 / PubMed Central
MethodsEM (single particle)
Resolution3.23 - 3.62 Å
Structure data

75696

11hm

EMDB-75696, PDB-11hm:
1332D4-RBD KP3.1.1 Complex
Method: EM (single particle) / Resolution: 3.56 Å

75698

11ho

EMDB-75698, PDB-11ho:
1332D4 Spike KP3.1.1 Complex
Method: EM (single particle) / Resolution: 3.26 Å

75725

11is

EMDB-75725, PDB-11is:
1332E5 Spike KP3.1.1 Complex
Method: EM (single particle) / Resolution: 3.23 Å

75726

11it

EMDB-75726, PDB-11it:
1332E5-RBD KP3.1.1 Complex Local Refine
Method: EM (single particle) / Resolution: 3.62 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • homo sapiens (human)
  • severe acute respiratory syndrome coronavirus 2
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / KP3.1.1 / Antibody / Complex / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / Fab

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