Impact of Protein Glycosylation on the Design of Viral Vaccines
Glycans play crucial roles in various biological processes such as cell proliferation, cell-cell interactions, and immune responses. Since viruses co-opt cellular biosynthetic pathways, viral glycosylation mainly depends on the host cell glycosylation mac
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Impact of Protein Glycosylation on the Design of Viral Vaccines Kathleen Schön, Bernd Lepenies, and Guillaume Goyette-Desjardins
Contents 1 Introduction 2 Protein N- and O-Glycosylation 2.1 Biosynthesis of N-Glycans in Mammals 2.2 Biosynthesis of N-Glycans in Insects 2.3 Biosynthesis of O-Glycans 3 Viral Glycosylation 3.1 Viral Glycans in the Replication of Enveloped Viruses 3.2 Viral Glycans in Immune Evasion 4 Viral Vaccine Design 4.1 Live-Attenuated Vaccines 4.2 Inactivated Vaccines 4.3 Subunit Vaccines 4.4 Influenza Virus: A Representative Example of the Importance of Glycosylation 5 Novel Glycan-Exploiting Vaccine Strategies 5.1 Sialylated Glycans with N-Glycolylneuraminic Acid 5.2 The α-Gal Epitope 5.3 Targeting CLRs: Mannose-Rich and Other Fungal Glycans 5.4 Insect-Produced Glycans 5.5 Plant-Produced Glycans 6 Perspectives References
K. Schön Immunology Unit and Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Hanover, Germany Institute for Parasitology, Centre for Infection Medicine, University of Veterinary Medicine Hannover, Hanover, Germany B. Lepenies (*) and G. Goyette-Desjardins (*) Immunology Unit and Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Hanover, Germany e-mail: [email protected]; [email protected]
K. Schön et al.
Abstract Glycans play crucial roles in various biological processes such as cell proliferation, cell-cell interactions, and immune responses. Since viruses co-opt cellular biosynthetic pathways, viral glycosylation mainly depends on the host cell glycosylation machinery. Consequently, several viruses exploit the cellular glycosylation pathway to their advantage. It was shown that viral glycosylation is strongly dependent on the host system selected for virus propagation and/or protein expression. Therefore, the use of different expression systems results in various glycoforms of viral glycoproteins that may differ in functional properties. These differences clearly illustrate that the choice of the expression system can be important, as the resulting glycosylation may influence immunological properties. In this review, we will first detail protein N- and O-glycosylation pathways and the resulting glycosylation patterns; we will then discuss different aspects of viral glycosylation in pathogenesis and in vaccine development; and finally, we will elaborate on how to harness viral glycosylation in order to optimize the design of viral vaccines. To this end, we will highlight specific examples to demonstrate how glycoengineering approaches and exploitation of different expression systems could pave the way towards better self-adjuvanted glycan-based viral vaccines. Graphical Abstract
Controlled by the choice of expression system
Novel strategies for glycan-based viral vaccines
Non-human and non-mammalian glycans - Neu5Gc-capped glycans - α-Gal-capped glycans - CLR targeting via mannose-rich glycans - Insect glycans - Plant glycans
Tailor-made
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