# Oriented Multivalent Display Drives Consistent Serum Immunodominance to the Ebola Virus Glycoprotein

## TL;DR

The study shows that how antigens are presented to the immune system affects the consistency of antibody responses, which could improve vaccine design.

## Contribution

The study reveals that oriented multivalent antigen presentation leads to consistent serum immunodominance across individuals.

## Key findings

- Trimeric GP caused varied epitope responses in individual animals.
- Multivalent GP on nanoparticles induced consistent epitope hierarchies in mice and guinea pigs.
- Oriented multivalent display may enhance uniform immune protection at the population level.

## Abstract

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.