biostudies-literatureUnknown12(1)Zheng CDespite the vast diversity of B cell repertoires, serum antibody responses during viral infection often focus on a limited set of epitopesa phenomenon known as immunodominance. This inherent bias establishes a hierarchy of epitope responses, which often facilitates viral immune evasion and presents a major challenge for universal vaccine design. It remains unclear whether serum immunodominance is primarily driven by antigen-intrinsic properties or by the spatial constraints imposed by virion-bound antigen presentation. Here, using Ebola virus glycoprotein (GP) as a model system, we found that trimeric GP elicited varied epitope hierarchies between individual animals during primary immunization. In contrast, multivalent GP presentation on either a vesicular stomatitis virus or ferritin nanACS central science100-110https://www.ebi.ac.uk/biostudies/studies/S-EPMC12856675biostudies-literatureOriented Multivalent Display Drives Consistent Serum Immunodominance to the Ebola Virus Glycoprotein.PMC12856675Kim PSPham DPan ZRubio AABarnes COZheng CVasquez SfalseOriented Multivalent Display Drives Consistent Serum Immunodominance to the Ebola Virus Glycoprotein.Despite the vast diversity of B cell repertoires, serum antibody responses during viral infection often focus on a limited set of epitopesa phenomenon known as immunodominance. This inherent bias establishes a hierarchy of epitope responses, which often facilitates viral immune evasion and presents a major challenge for universal vaccine design. It remains unclear whether serum immunodominance is primarily driven by antigen-intrinsic properties or by the spatial constraints imposed by virion-bound antigen presentation. Here, using Ebola virus glycoprotein (GP) as a model system, we found that trimeric GP elicited varied epitope hierarchies between individual animals during primary immunization. In contrast, multivalent GP presentation on either a vesicular stomatitis virus or ferritin nan2026-01-01T00:00:00Z2026 Jan2026-06-18T05:52:35.683Z2026-06-18T03:07:24.806ZS-EPMC128566754162522510.1021/acscentsci.5c01886