Influence of glycosylation on the immunogenicity and antigenicity of viral immunogens
Influence of glycosylation on the immunogenicity and antigenicity of viral immunogens
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.
Glycoprotein, Glycosylation, Immunogen, Vaccine, Virus
Newby, Maddy L.
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Allen, Joel D.
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Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
18 November 2023
Newby, Maddy L.
417cba47-6a6f-42b9-8b9c-640f0518c621
Allen, Joel D.
c89d5569-7659-4835-b535-c9586e956b3a
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Newby, Maddy L., Allen, Joel D. and Crispin, Max
(2023)
Influence of glycosylation on the immunogenicity and antigenicity of viral immunogens.
Biotechnology Advances, 70, [108283].
(doi:10.1016/j.biotechadv.2023.108283).
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.
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Accepted/In Press date: 9 November 2023
e-pub ahead of print date: 14 November 2023
Published date: 18 November 2023
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Funding Information:
This work is supported by the International AIDS Vaccine Initiative , the Bill and Melinda Gates Foundation through the Collaboration for AIDS Discovery (OPP1084519 and OPP1115782), and the US National Institute of Allergy and Infectious Diseases (1U01AI169587; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, UM1AI100663) to M.C.. Figures were generated using BioRender ( www.biorender.com ) and ChimeraX ( Pettersen et al., 2021 ).
Keywords:
Glycoprotein, Glycosylation, Immunogen, Vaccine, Virus
Identifiers
Local EPrints ID: 486078
URI: http://eprints.soton.ac.uk/id/eprint/486078
ISSN: 0734-9750
PURE UUID: d2179ef6-752d-4fc7-8d85-31d49fcf2320
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Date deposited: 09 Jan 2024 17:30
Last modified: 18 Mar 2024 04:03
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Author:
Maddy L. Newby
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