Recombinant Glycoprotein E of Varicella Zoster Virus Contains Glycan-Peptide Motifs That Modulate B Cell Epitopes into Discrete Immunological Signatures

Autor: Rickard Nordén, Ebba Samuelsson, Tomas Bergström, Sigvard Olofsson, Carina Sihlbom, Christian Risinger, Göran Larson, Jonas Nilsson, Ola Blixt
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Serum
Acetylgalactosamine
glycoprotein E
medicine.disease_cause
law.invention
lcsh:Chemistry
chemistry.chemical_compound
0302 clinical medicine
Viral Envelope Proteins
law
immune system diseases
hemic and lymphatic diseases
Cricetinae
vaccine
030212 general & internal medicine
varicella zoster virus
lcsh:QH301-705.5
Spectroscopy
Attenuated vaccine
biology
Chemistry
Chinese hamster ovary cell
hemic and immune systems
General Medicine
Recombinant Proteins
Computer Science Applications
Recombinant DNA
antibody binding
B cell epitope
Epitopes
B-Lymphocyte
Glycan
Glycosylation
glycosylation
chemical and pharmacologic phenomena
CHO Cells
Catalysis
Virus
Article
Inorganic Chemistry
03 medical and health sciences
Cricetulus
Polysaccharides
medicine
Animals
Humans
Amino Acid Sequence
Physical and Theoretical Chemistry
Molecular Biology
Organic Chemistry
Varicella zoster virus
Vaccine efficacy
Virology
carbohydrates (lipids)
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
biology.protein
Peptides
Zdroj: International Journal of Molecular Sciences, Vol 20, Iss 4, p 954 (2019)
International Journal of Molecular Sciences
Nordén, R, Nilsson, J, Samuelsson, E, Risinger, C, Sihlbom, C, Blixt, O, Larson, G, Olofsson, S & Bergström, T 2019, ' Recombinant Glycoprotein E of Varicella Zoster Virus Contains Glycan-Peptide Motifs That Modulate B Cell Epitopes into Discrete Immunological Signatures ', International Journal of Molecular Sciences (Online), vol. 20, no. 4, 954 . https://doi.org/10.3390/ijms20040954
Volume 20
Issue 4
ISSN: 1422-0067
DOI: 10.3390/ijms20040954
Popis: A recombinant subunit vaccine (Shingrix®
) was recently licensed for use against herpes zoster. This vaccine is based on glycoprotein E (gE) of varicella zoster virus (VZV), the most abundantly expressed protein of VZV, harboring sites for N- and O-linked glycosylation. The subunit vaccine elicits stronger virus-specific CD4+ T cell response as well as antibody B cell response to gE, compared to the currently used live attenuated vaccine (Zostavax®
). This situation is at variance with the current notion since a live vaccine, causing an active virus infection, should be far more efficient than a subunit vaccine based on only one single viral glycoprotein. We previously found gE to be heavily glycosylated, not least by numerous clustered O-linked glycans, when it was produced in human fibroblasts. However, in contrast to Zostavax®
which is produced in fibroblasts, the recombinant gE of Shingrix®
is expressed in Chinese hamster ovary (CHO) cells. Hence, the glycan occupancy and glycan structures of gE may differ considerably between the two vaccine types. Here, we aimed at (i) defining the glycan structures and positions of recombinant gE and (ii) identifying possible features of the recombinant gE O-glycosylation pattern contributing to the vaccine efficacy of Shingrix®
Firstly, recombinant gE produced in CHO cells (&ldquo
Shingrix situation&rdquo
) is more scarcely decorated by O-linked glycans than gE from human fibroblasts (&ldquo
Zostavax situation&rdquo
), with respect to glycan site occupancy. Secondly, screening of immunodominant B cell epitopes of gE, using a synthetic peptide library against serum samples from VZV-seropositive individuals, revealed that the O-linked glycan signature promoted binding of IgG antibodies via a decreased number of interfering O-linked glycans, but also via specific O-linked glycans enhancing antibody binding. These findings may, in part, explain the higher protective efficacy of Shingrix®
and can also be of relevance for development of subunit vaccines to other enveloped viruses.
Databáze: OpenAIRE
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