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 ("Shingrix situation") is more scarcely decorated by O-linked
glycans than gE from human fibroblasts ("
Zostavax situation"), 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.