FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2952809212> ?p ?o ?g. }

• W2952809212 abstract "Influenza viruses cause significant morbidity and mortality worldwide. Vaccines are the best tools available to reduce the disease burden; however, vaccine effectiveness varies significantly between years, target populations and strains. Medicago Inc. has developed a highly efficient platform to produce plant-derived virus-like particle (VLP) vaccines bearing influenza hemagglutinin (HA) that have been shown to elicit strong humoral and CD4+ T cell responses in both pre-clinical and clinical studies. To better understand the immunogenicity of these vaccines, we studied the early interactions of VLPs with antigen-presenting cells (APC) in vitro. We demonstrated that VLPs bind to human monocytoid U-937 cells and monocyte-derived macrophages (MDMs) in a sialic acid-dependent manner. VLP attachment to the cell surface led to internalization, trafficking to acidic cell compartments and fusion of the VLP lipid envelope with endosomal membranes. Incubation of MDMs with VLPs bearing H1 (HA sequence from A/California/07/2009 (H1N1) strain) but not H5 (HA sequence from A/Indonesia/05/2005 (H5N1) induced proliferation of autologous lymphoid cells suggesting antigen processing by MDMs and stimulation of a memory T cell response. Pulse-exposure of MDMs with H1-VLPs resulted in a rapid and massive intracellular accumulation of HA that was driven by clathrin-mediated and clathrin-independent endocytosis as well as macropinocytosis/phagocytosis. The H1-VLPs endosomal distribution pattern suggested that HA delivered by VLP had entered both high-degradative late (supporting major histocompatibility complex (MHC) II-restricted antigen presentation) and low-degradative static early and/or recycling (favoring MHC I-restricted antigen cross-presentation) endosomal pathways. High-resolution tandem mass spectrometry identified a large number of HA-derived peptides associated with MHC I in the H1-VLP-treated MDMs. In addition, many host-derived MHC I peptides were identified in VLP-treated samples. These peptides were mainly processed by matrix metalloproteinases and cathepsins. The host proteins associated with these peptides were primarily involved in pathways modulating inflammation (i.e. stimulation and attenuation), innate and adaptive immunity, clathrin-mediated endocytosis, protein synthesis and endo-lysosomal degradation. Finally, tools we used while studying endosome-lysosome fusion led to the development of a novel serological assay for influenza based on 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine perchlorate (DiD) fluorescence dequenching. This assay measures 'functional' influenza antibody titers, is free from observer bias and has the potential to be fully automated. In summary, we demonstrated that HA delivery to APCs in a form of plant-derived VLPs facilitates antigen uptake, endosomal processing, presentation and cross-presentation. These observations may help to explain the broad and cross-reactive immune responses generated by VLP vaccines. The new DiD fluorescence dequenching assay we developed may give new…" @default.
• W2952809212 created "2019-06-27" @default.
• W2952809212 creator A5046502858 @default.
• W2952809212 date "2019-01-01" @default.
• W2952809212 modified "2023-09-26" @default.
• W2952809212 title "Influenza vaccine development: immunogenicity and correlates of protection" @default.
• W2952809212 hasPublicationYear "2019" @default.
• W2952809212 type Work @default.
• W2952809212 sameAs 2952809212 @default.
• W2952809212 citedByCount "0" @default.
• W2952809212 crossrefType "journal-article" @default.
• W2952809212 hasAuthorship W2952809212A5046502858 @default.
• W2952809212 hasConcept C139770010 @default.
• W2952809212 hasConcept C147483822 @default.
• W2952809212 hasConcept C1491633281 @default.
• W2952809212 hasConcept C159047783 @default.
• W2952809212 hasConcept C203014093 @default.
• W2952809212 hasConcept C2522874641 @default.
• W2952809212 hasConcept C2776090121 @default.
• W2952809212 hasConcept C2778692840 @default.
• W2952809212 hasConcept C2780868878 @default.
• W2952809212 hasConcept C28005876 @default.
• W2952809212 hasConcept C55493867 @default.
• W2952809212 hasConcept C83464605 @default.
• W2952809212 hasConcept C86803240 @default.
• W2952809212 hasConcept C8891405 @default.
• W2952809212 hasConcept C89423630 @default.
• W2952809212 hasConceptScore W2952809212C139770010 @default.
• W2952809212 hasConceptScore W2952809212C147483822 @default.
• W2952809212 hasConceptScore W2952809212C1491633281 @default.
• W2952809212 hasConceptScore W2952809212C159047783 @default.
• W2952809212 hasConceptScore W2952809212C203014093 @default.
• W2952809212 hasConceptScore W2952809212C2522874641 @default.
• W2952809212 hasConceptScore W2952809212C2776090121 @default.
• W2952809212 hasConceptScore W2952809212C2778692840 @default.
• W2952809212 hasConceptScore W2952809212C2780868878 @default.
• W2952809212 hasConceptScore W2952809212C28005876 @default.
• W2952809212 hasConceptScore W2952809212C55493867 @default.
• W2952809212 hasConceptScore W2952809212C83464605 @default.
• W2952809212 hasConceptScore W2952809212C86803240 @default.
• W2952809212 hasConceptScore W2952809212C8891405 @default.
• W2952809212 hasConceptScore W2952809212C89423630 @default.
• W2952809212 hasLocation W29528092121 @default.
• W2952809212 hasOpenAccess W2952809212 @default.
• W2952809212 hasPrimaryLocation W29528092121 @default.
• W2952809212 hasRelatedWork W139890194 @default.
• W2952809212 hasRelatedWork W1537147943 @default.
• W2952809212 hasRelatedWork W184552897 @default.
• W2952809212 hasRelatedWork W2007340000 @default.
• W2952809212 hasRelatedWork W2048479947 @default.
• W2952809212 hasRelatedWork W2071726327 @default.
• W2952809212 hasRelatedWork W2082134991 @default.
• W2952809212 hasRelatedWork W2084480062 @default.
• W2952809212 hasRelatedWork W2102990388 @default.
• W2952809212 hasRelatedWork W2140504124 @default.
• W2952809212 hasRelatedWork W2156472928 @default.
• W2952809212 hasRelatedWork W2160576748 @default.
• W2952809212 hasRelatedWork W2548461336 @default.
• W2952809212 hasRelatedWork W2742418645 @default.
• W2952809212 hasRelatedWork W2895165331 @default.
• W2952809212 hasRelatedWork W2900523742 @default.
• W2952809212 hasRelatedWork W2908867824 @default.
• W2952809212 hasRelatedWork W3047529002 @default.
• W2952809212 hasRelatedWork W3090303973 @default.
• W2952809212 hasRelatedWork W2131274553 @default.
• W2952809212 isParatext "false" @default.
• W2952809212 isRetracted "false" @default.
• W2952809212 magId "2952809212" @default.
• W2952809212 workType "article" @default.