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TitleOriented Multivalent Display Drives Consistent Serum Immunodominance to the Ebola Virus Glycoprotein.
Journal, issue, pagesACS Cent Sci, Vol. 12, Issue 1, Page 100-110, Year 2026
Publish dateJan 28, 2026
AuthorsChu Zheng / Adonis A Rubio / Sheena Vasquez / Dominic Pham / Zhuangyu Pan / Christopher O Barnes / Peter S Kim /
PubMed AbstractDespite 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 ...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 nanoparticlesin the native orientation found on the Ebola viruselicited highly consistent and more refined epitope hierarchies across multiple mice and guinea pigs. These findings reveal a key role of oriented multivalent presentation in shaping serum immunodominance. The striking consistency of epitope hierarchy among individuals suggests that oriented multivalent presentation may promote more uniform immune protection at the population level, beyond increasing the magnitude of antibody binding and neutralizing responses.
External linksACS Cent Sci / PubMed:41625225 / PubMed Central
MethodsEM (single particle)
Resolution15.0 Å
Structure data

EMDB-72372: Polyclonal immune complex of guinea pig Fab from sera binding Ebola glycoprotein (nsEM, GP-trimer map 4)
Method: EM (single particle) / Resolution: 15.0 Å

EMDB-72373: Polyclonal immune complex of guinea pig Fab from sera binding Ebola glycoprotein (nsEM, GP-Ferritin map 1)
Method: EM (single particle) / Resolution: 15.0 Å

EMDB-72374: Polyclonal immune complex of guinea pig Fab from sera binding Ebola glycoprotein (nsEM, GP-Ferritin map 2)
Method: EM (single particle) / Resolution: 15.0 Å

EMDB-72375: Polyclonal immune complex of guinea pig Fab from sera binding Ebola glycoprotein (nsEM, GP-Ferritin map 3)
Method: EM (single particle) / Resolution: 15.0 Å

Source
  • Ebola virus - Mayinga, Zaire, 1976
  • Cavia porcellus (domestic guinea pig)

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