Dataset Information

Glycosylation profiling of Influenza A Virus H3 HA

ABSTRACT: The quest for a universal influenza vaccine holds great promise for mitigating the global burden of influenza-related morbidity and mortality. Despite significant progress, challenges persist in identifying conserved epitopes capable of inducing broadly protective immune responses, understanding the correlates of protection against influenza infection, and ensuring vaccine safety and efficacy across diverse populations. In this study, we explore the influence of glycan evolution on H3 HA from 1968 to the present. Our in-depth analysis unveiled how glycan addition significantly and differentially impacted HA antigenicity and immunogenicity over time. We observe that adding glycans influenced the polyclonal immune response elicited post-immunization. We propose that the appearance of PNGS at N158 potentially impacted the binding of head-specific broadly neutralizing antibodies (bnAbs). We further observe that, while enzymatic de-glycosylation barely impacted HK/68 HA stability, it destabilized and unfolded in the hyperglycosylated head domain and the membrane-proximal region of the stem domain in Sing/16. These insights expand our understanding of glycans beyond their conventional role in protein folding and as immune evasion tactics and highlight the intricate interplay among glycan integration, viral fitness, and immune recognition. Our findings have implications for vaccine design and manufacturing processes, offering valuable insights for developing more effective influenza vaccines. Moreover, they contribute to ongoing efforts to refine influenza research strategies, emphasizing the potential of stem-directed antibodies in creating more effective and universally applicable influenza vaccines.

INSTRUMENT(S):

ORGANISM(S): Influenza A Virus

SUBMITTER: Joost Snijder

LAB HEAD: Joost Snijder

PROVIDER: PXD051492 | Pride | 2026-01-12

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	200205_IAV_01_Sing16.fasta	Fasta
	200205_IAV_03_HK-68.fasta	Fasta
	20250425_E1_UM4_plitt001_SA_EXT00_HK_chy_1.raw	Raw
	20250425_E1_UM4_plitt001_SA_EXT00_HK_chy_1.raw_20250520_1051.zip	Raw
	20250425_E1_UM4_plitt001_SA_EXT00_HK_chy_1_2.raw	Raw

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Publications

Structural and immunological characterization of the H3 influenza hemagglutinin during antigenic drift.

de Paiva Froes Rocha Rebeca R Tomris Ilhan I Bowman Charles A CA Stevens Emma E Kantorow Jason J Plitt Corinna M CM Peng Weiwei W Oeverdieck Svearike S Galdino Andrade Thales T Ferguson James A JA Jung Diana D DD Marques Rafael Elias RE Herfst Sander S Snijder Joost J Chakraborty Srirupa S Torrents de la Peña Alba A Berndsen Zachary T ZT de Vries Robert P RP Ward Andrew B AB

Nature communications 20251211 1

The quest for a universal influenza vaccine holds great promise for mitigating the global burden of influenza-related morbidity and mortality. However, challenges persist in identifying conserved epitopes capable of eliciting robust and durable immune responses. In this study, we explore the influence of glycan evolution on H3 hemagglutinin from 1968 to present day and its impacts on protein structure, antigenicity and immunogenicity by using computational, biochemical and biophysical techniques ...[more]

PMID: 41381528

Similar Datasets

Project description:Influenza A virus (IAV) mutates rapidly, preventing a single seasonal vaccine from targeting more than one strain, and year-to-year vaccine effectiveness is low. One challenge in designing effective vaccines is that genetic mutations frequently cause amino acid variations in IAV envelope protein hemagglutinin (HA) that create new N-glycosylation sequons; resulting N-glycans cause antigenic shielding, allowing viral escape from adaptive immune responses. Vaccine candidate strain selection currently involves correlating antigenicity with HA protein sequence among circulating strains, but quantitative comparison of site-specific glycosylation information is likely to improve the ability to design vaccines with broader effectiveness against evolved strains. However, there is poor understanding of the influence of glycosylation on immunodominance, antigenicity, and immunogenicity of HA, and there are no well-tested methods for comparing glycosylation similarity among virus samples. Here, we present a method for statistically rigorous quantification of similarity between two related virus strains that considers the presence and abundance of glycopeptide glycoforms. We demonstrate the strength of our approach by determining that there was a quantifiable difference in glycosylation at the protein level between wild-type IAV HA from A/Switzerland/9715293/2013 (SWZ13) and a mutant strain of SWZ13, even though no N-glycosylation sequons were changed. We determined site-specifically that WT and mutant HA have varying similarity at the glycosylation sites of the head domain, reflecting competing pressures to evade host immune response while retaining viral fitness. To our knowledge, our results are the first to quantify changes in glycosylation state that occur in related proteins of considerable glycan heterogeneity. Our results provide a method for understanding how changes in glycosylation state are correlated with variations in protein sequence, which is necessary for improving IAV vaccine strain selection. Understanding glycosylation will be especially important as we find new expression vectors for vaccine production, as glycosylation state depends greatly on the host species.