Volume 70, January–February 2024, 108283Author links open overlay panel, , Highlights•

The development of viral glycoprotein mimetics has accelerated viral vaccinology

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Viral glycosylation exhibits wide implications in viral function and immunogenicity

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Native-like glycan mimicry is often important for effective vaccine design

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Glycoengineering strategies have been shown to improve immunogen antigenicity

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Continued glycoengineering innovation will be crucial for future vaccine design

Abstract

A key aspect of successful viral vaccine design is the elicitation of neutralizing antibodies targeting viral attachment and fusion glycoproteins that embellish viral particles. This observation has catalyzed the development of numerous viral glycoprotein mimetics as vaccines. Glycans can dominate the surface of viral glycoproteins and as such, the viral glycome can influence the antigenicity and immunogenicity of a candidate vaccine. In one extreme, glycans can form an integral part of epitopes targeted by neutralizing antibodies and are therefore considered to be an important feature of key immunogens within an immunization regimen. In the other extreme, the existence of peptide and bacterially expressed protein vaccines shows that viral glycosylation can be dispensable in some cases. However, native-like glycosylation can indicate native-like protein folding and the presence of conformational epitopes. Furthermore, going beyond native glycan mimicry, in either occupancy of glycosylation sites or the glycan processing state, may offer opportunities for enhancing the immunogenicity and associated protection elicited by an immunogen. Here, we review key determinants of viral glycosylation and how recombinant immunogens can recapitulate these signatures across a range of enveloped viruses, including HIV-1, Ebola virus, SARS-CoV-2, Influenza and Lassa virus. The emerging understanding of immunogen glycosylation and its control will help guide the development of future vaccines in both recombinant protein- and nucleic acid-based vaccine technologies.

Keywords

Glycoprotein

Virus

Glycosylation

Vaccine

Immunogen

AbbreviationsbnAb

broadly neutralizing antibody

CDR

complementarity determining region

EMPEM

electron microscopy polyclonal epitope mapping

ERAD

ER-associated degradation

GlcNAc

N-acetylglucosamine

GnTI

N-acetylglucosaminyltransferase

GPI

glycosyl phosphatidylinositol

HIV-1

Human immuno deficiency virus 1

HLA

Human leukocyte antigen

IMP

intrinsic mannose patch

LAMP-1

lysosomal-associated membrane protein 1

LRT

lower respiratory tract

MBL

mannose binding lectin

MPER

membrane-proximal external region

Neu5Ac

N-acetylneuraminic acid

Neu5Gc

N-glycolylneuraminic acid

NFL

natively flexibly linked

OST

oligosaccharyltransferase

PNGS

potential N-linked glycosylation site

RBD

receptor binding domain

SHM

somatic hyper mutation

TAMP

trimer associated mannose patch

UFO

uncleaved prefusion-optimized

UGG7

UDP-glucose:glycoprotein glucosyltransferase

URT

upper respiratory tract

© 2023 The Authors. Published by Elsevier Inc.