ArticleCommunications medicine2025
Modifying the glycosylation profile of SARS-CoV-2 spike-based subunit vaccines alters focusing of the humoral immune response in a mouse model.
Article in Communications medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Site-Specific Glycosylation Profiling of Protein Subunit and Inactivated Virus Vaccines.Vaccines · 2026Article
- Nucleocapsid protein enhances spike- and RBD-specific humoral and cellular immune responses in protein-based SARS-CoV-2 vaccine.BMC infectious diseases · 2026Article
- Rewriting the viral script: post-translational modifications orchestrating SARS-CoV-2 pathogenesis and immune evasion.Frontiers in microbiology · 2026Review
- Architects of folding, editors of immunity: the strategic use ofFrontiers in immunology · 2026Article
- A Safe and Accessible Cell-Based Spike-ACE2 Binding Assay for Evaluating SARS-CoV-2 Neutralization Activity in Biological Samples Using Flow Cytometry.Methods and protocols · 2025Article
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Authors and funding
21 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundProtein subunit vaccines have a strong track record of efficacy and safety and have been widely applied for prevention of a variety of infectious diseases. The impacts of post-translational modifications of vaccine antigens are often overlooked, despite the fact that they can vary significantly depending on the expression hosts (e.g., bacteria, yeast, plant, insect or mammalian cells) and the culture conditions used for their manufacturing.
methodsUsing SARS-CoV-2 spike trimers as model antigens, we sought to evaluate the immunological impact of modulating their state of glycosylation. Spike proteins rich in complex-type (CT), high-mannose (HM) or paucimannose (PM) N-linked glycans were produced using Chinese Hamster Ovary (CHO) cells (cultured with or without the mannosidase inhibitor kifunensine) or insect cells.
resultsHere we show that when these antigens are adjuvanted with liposomes composed of sulfated lactosyl archaeol (SLA), all glycoforms are highly immunogenic and induce abundant spike-specific serum IgG and IFN-γ producing T-cells within female C57BL/6 mice. The spike antigen with CT glycans induces a significantly more potent neutralizing immune response, which directly correlates to more abundant receptor binding domain (RBD)-specific IgG when comparing to the antigen with HM glycans. This observation remains true whether the spike is resistin- or T4 foldon-trimerized, indicating that the glycosylation effect is not trimerization domain-specific. Spike with PM glycans induces remarkably low titers of neutralizing antibodies and RBD-specific IgG.
conclusionsThe results highlight the significant impacts of a vaccine's antigen glycosylation profile in directing the immune response, which should be an important consideration for designing efficient protein-based vaccines.
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Registered trials
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