Complexity of Viral Epitope Surfaces as Evasive Targets for Vaccines and Therapeutic Antibodies

Front Immunol. 2022 Jun 17;13:904609. doi: 10.3389/fimmu.2022.904609. eCollection 2022.

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.

Keywords: N-glycan; SARS-CoV-2; antibody; epitope; escape; glycoepitope; paratope; repurposing.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies
  • Antigens, Viral
  • Binding Sites, Antibody
  • Epitopes
  • Vaccines*

Substances

  • Antibodies
  • Antigens, Viral
  • Epitopes
  • Vaccines