Complexity of Viral Epitope Surfaces as Evasive Targets for Vaccines and Therapeutic Antibodies
Name
fimmu-13-904609.pdf
Description
Published version
Size
1.73 MB
Format
Adobe PDF
Checksum (MD5)
b8377f931f42e677b55f6fd19552abb4
Author(s)
Miller, Nathaniel L
Raman, Rahul
Clark, Thomas
Sasisekharan, Ram
Date Issued
2022
Journal
Frontiers in Immunology
Publisher
Frontiers Media SA
Citation
Miller, Nathaniel L, Raman, Rahul, Clark, Thomas and Sasisekharan, Ram. 2022. "Complexity of Viral Epitope Surfaces as Evasive Targets for Vaccines and Therapeutic Antibodies." Frontiers in Immunology, 13.
Version
Final published version
Abstract
The dynamic interplay between virus and host plays out across many interacting surfaces as virus and host evolve continually in response to one another. In particular, epitope-paratope interactions (EPIs) between viral antigen and host antibodies drive much of this evolutionary race. In this review, we describe a series of recent studies examining aspects of epitope complexity that go beyond two interacting protein surfaces as EPIs are typically understood. To structure our discussion, we present a framework for understanding epitope complexity as a spectrum along a series of axes, focusing primarily on 1) epitope biochemical complexity (e.g., epitopes involving N-glycans) and 2) antigen conformational/dynamic complexity (e.g., epitopes with differential properties depending on antigen state or fold-axis). We highlight additional epitope complexity factors including epitope tertiary/quaternary structure, which contribute to epistatic relationships between epitope residues within- or adjacent-to a given epitope, as well as epitope overlap resulting from polyclonal antibody responses, which is relevant when assessing antigenic pressure against a given epitope. Finally, we discuss how these different forms of epitope complexity can limit EPI analyses and therapeutic antibody development, as well as recent efforts to overcome these limitations.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.3389/fimmu.2022.904609
