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          Institute: MPI für Dynamik komplexer technischer Systeme     Collection: Bioprocess Engineering     Display Documents

ID: 571758.0, MPI für Dynamik komplexer technischer Systeme / Bioprocess Engineering
Impact of Influenza A virus hemagglutinin N-glycosylation on immunogenicity
Authors:Hütter, J; Rödig, J.; Reichl, U.; Seeberger, P H; Rapp, E.; Lepenies, B
Date of Publication (YYYY-MM-DD):2011
Title of Journal:Glycoconjugate Journal
Volume (in Journal):28
Issue / Number:5 - Special Issue : XXI International Symposium on Glycoconjugates
Start Page:305
End Page:305
Name of Conference/Meeting:21st International Symposium on Glycoconjugates (Glyco 21)
Place of Conference/Meeting:Wien, Östereich
(Start) Date of Conference/Meeting
End Date of Conference/Meeting 
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Glycosylation of infl uenza virus proteins is host dependent and can infl uence protein properties such as structural stability, protease resistence, or biological activity. It has already been reported that hemagglutinin (HA) from the infl uenza A H1N1/PR/8/34/RKI strain propagated in various cell lines exhibits distinct N-glycosylation patterns. However, it is still discussed whether and in which way differential glycosylation effects immunogenicity of the virus. In this study, we investigated whether the difference in the N-glycosylation pattern of infl uenza A virus produced in MDCK cells (M-variant) or Vero cells (V-variant) had an impact on virus immunogenicity. For this purpose, a stimulation assay using TCR-HA transgenic spleen cells was performed. All T cells from TCR-HA transgenic mice have an αβ T cell receptor specific for the peptide 110-120 from infl uenza HA presented by I-Ed MHC class II molecules. In this assay, a signifi cant difference in the up-regulation of the T cell activation marker CD69 and in cytokine production was observed. Spleen cells incubated with the V-variant up-regulated CD69 faster and to a signifi cantly higher extent than splenocytes incubated with the M-variant. Additionally, the V-variant led to a signifi cantly increased secretion of IL-2. In contrary, spleen cells incubated with the M-variant secreted higher levels of effector cytokines such as IL-4 and IFN-γ. The difference in the immunostimulatory effect can be due to a differential uptake and/or processing of virus derived proteins or recognition by different lectin receptors leading to the activation of distinct signaling pathways. In conclusion, we show that virus protein glycosylation has a signifi cant effect on immunogenicity. This finding might have important implications for infl uenza vaccine manufacturing. In vivo immunization studies with TCR-HA transgenic mice are currently ongoing.
External Publication Status:published
Document Type:Conference-Paper
Communicated by:Udo Reichl
Affiliations:MPI für Dynamik komplexer technischer Systeme/Bioprocess Engineering
Identifiers:URL:http://dx.doi.org/10.1007/s10719-011-9334-5 [Abstract]
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