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Sökning: WFRF:(Risinger C)

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1.
  • Hinkula, Jorma, et al. (författare)
  • Immunization with DNA Plasmids Coding for Crimean-Congo Hemorrhagic Fever Virus Capsid and Envelope Proteins and/or Virus-Like Particles Induces Protection and Survival in Challenged Mice
  • 2017
  • Ingår i: Journal of Virology. - : AMER SOC MICROBIOLOGY. - 0022-538X .- 1098-5514. ; 91:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Crimean-Congo hemorrhagic fever virus (CCHFV) is a bunyavirus causing severe hemorrhagic fever disease in humans, with high mortality rates. The requirement of a high-containment laboratory and the lack of an animal model hampered the study of the immune response and protection of vaccine candidates. Using the recently developed interferon alpha receptor knockout (IFNAR(- / -)) mouse model, which replicates human disease, we investigated the immunogenicity and protection of two novel CCHFV vaccine candidates: a DNA vaccine encoding a ubiquitin-linked version of CCHFV Gc, Gn, and N and one using transcriptionally competent virus-like particles (tc-VLPs). In contrast to most studies that focus on neutralizing antibodies, we measured both humoral and cellular immune responses. We demonstrated a clear and 100% efficient preventive immunity against lethal CCHFV challenge with the DNA vaccine. Interestingly, there was no correlation with the neutralizing antibody titers alone, which were higher in the tc-VLP-vaccinated mice. However, the animals with a lower neutralizing titer, but a dominant cell-mediated Th1 response and a balanced Th2 response, resisted the CCHFV challenge. Moreover, we found that in challenged mice with a Th1 response (immunized by DNA/DNA and boosted by tc-VLPs), the immune response changed to Th2 at day 9 postchallenge. In addition, we were able to identify new linear B-cell epitope regions that are highly conserved between CCHFV strains. Altogether, our results suggest that a predominantly Th1-type immune response provides the most efficient protective immunity against CCHFV challenge. However, we cannot exclude the importance of the neutralizing antibodies as the surviving immunized mice exhibited substantial amounts of them. IMPORTANCE Crimean-Congo hemorrhagic fever virus (CCHFV) is responsible for hemorrhagic diseases in humans, with a high mortality rate. There is no FDAapproved vaccine, and there are still gaps in our knowledge of the immune responses to infection. The recently developed mouse models mimic human CCHF disease and are useful to study the immunogenicity and the protection by vaccine candidates. Our study shows that mice vaccinated with a specific DNA vaccine were fully protected. Importantly, we show that neutralizing antibodies are not sufficient for protection against CCHFV challenge but that an extra Th1-specific cellular response is required. Moreover, we describe the identification of five conserved B-cell epitopes, of which only one was previously known, that could be of great importance for the development of diagnostics tools and the improvement of vaccine candidates.
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  • Figgemeier, Egbert, et al. (författare)
  • Modification of electron transfer properties in photoelectrochemical solar cells by substituting {Ru(terpy)(2)}(2+) dyes with thiophene
  • 2004
  • Ingår i: Inorganic Chemistry Communications. - 1387-7003 .- 1879-0259. ; 7:1, s. 117-121
  • Tidskriftsartikel (refereegranskat)abstract
    • A comparison of the properties of the 2-thienyl-substituted carboxyphenyl {RuII(terpy)2} dyes with their non-substituted analogues has enabled us to gain insight into the electronic properties that are prerequisite for efficient electron injection into the TiO2 conduction band in photoelectrochemical solar cells. Introducing the thienyl group has a profound effect upon the efficiency of photoinduced electron injection. This effect can be explained by a significant shift in the LUMO position from the terpy ligand anchored on the TiO2 surface towards the 2-thienyl substituted ligand, which is shown by means of electrochemistry and semiempirical calculations.
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  • Nordén, Rickard, et al. (författare)
  • Recombinant Glycoprotein E of Varicella Zoster Virus Contains Glycan-Peptide Motifs That Modulate B Cell Epitopes into Discrete Immunological Signatures
  • 2019
  • Ingår i: International Journal of Molecular Sciences. - 1422-0067. ; 20:4
  • Tidskriftsartikel (refereegranskat)abstract
    • A recombinant subunit vaccine (Shingrix((R))) 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((R))). 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((R)), which is produced in fibroblasts, the recombinant gE of Shingrix((R)) 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((R)). 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((R)), and can also be of relevance for development of subunit vaccines to other enveloped viruses.
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  • Resultat 1-10 av 14
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