Modification of Asparagine-Linked Glycan Density for the Design of Hepatitis B Virus Virus-Like Particles with Enhanced Immunogenicity

Journal of Virology
Michiko HyakumuraHans J Netter

Abstract

The small envelope proteins (HBsAgS) derived from hepatitis B virus (HBV) represent the antigenic components of the HBV vaccine and are platforms for the delivery of foreign antigenic sequences. To investigate structure-immunogenicity relationships for the design of improved immunization vectors, we have generated biochemically modified virus-like particles (VLPs) exhibiting glycoengineered HBsAgS. For the generation of hypoglycosylated VLPs, the wild-type (WT) HBsAgS N146 glycosylation site was converted to N146Q; for constructing hyperglycosylated VLPs, potential glycosylation sites were introduced in the HBsAgS external loop region at positions T116 and G130 in addition to the WT site. The introduced T116N and G130N sites were utilized as glycosylation anchors resulting in the formation of hyperglycosylated VLPs. Mass spectroscopic analyses showed that the hyperglycosylated VLPs carry the same types of glycans as WT VLPs, with minor variations regarding the degree of fucosylation, bisecting N-acetylglucosamines, and sialylation. Antigenic fingerprints for the WT and hypo- and hyperglycosylated VLPs using a panel of 19 anti-HBsAgS monoclonal antibodies revealed that 15 antibodies retained their ability to bind to the differen...Continue Reading

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Citations

Apr 18, 2016·Molecular Aspects of Medicine·Ian LokeMorten Thaysen-Andersen
Aug 16, 2016·Journal of Proteome Research·Ling Y LeeMorten Thaysen-Andersen
Mar 27, 2018·Glycobiology·Ieva Bagdonaite, Hans H Wandall
Aug 6, 2019·Liver International : Official Journal of the International Association for the Study of the Liver·Renae WalshStephen Locarnini
Apr 25, 2020·Mass Spectrometry Reviews·David J Harvey
Jun 10, 2020·Cells·Mihaela-Olivia DobricaNorica Branza-Nichita
Nov 25, 2020·Vaccines·Nathaniel Nyakaat NinyioAbdul Razak Mariatulqabtiah
Mar 7, 2021·Vaccines·Mei-Ling LiGary Brewer
Nov 1, 2021·Journal of Molecular Biology·Himanshi ChawlaMax Crispin

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