Valérie Künzi

AVACO AG, Switzerland, Basel-Landschaft, Switzerland

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Publications (7)30.13 Total impact

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    ABSTRACT: Despite the established benefit of intramuscular (i.m.) influenza vaccination, new adjuvants and delivery methods for comparable or improved immunogenicity are being explored. Intradermal (i.d.) antigen administration is hypothesized to initiate an efficient immune response at reduced antigen doses similar to that observed after i.m. full dose vaccination. In a randomized, partially blinded phase II study 224, healthy adults aged >or=18 to <or=60 years were randomly assigned to four groups and received trivalent influenza vaccine at single doses of 3.0, 4.5 and 6.0 microg hemagglutinin (HA) antigen of each influenza virus strain via i.d. injection or 15.0 microg HA of each influenza strain via i.m. delivery. Serum anti-influenza virus antibodies were determined by hemagglutination inhibition (HI) assay before and 3 weeks after vaccination. Safety assessments were made at baseline and at the follow-up visit by the investigators and for a 4-day period post-vaccination by the subjects themselves. The EMEA requirements for re-licensing of influenza vaccines were fulfilled in all groups 3 weeks after vaccination, irrespective of dose and mode of administration. High seroconversion rates were observed in all study groups and for all strains ranging from 50.9 to 85.5% and 70.4 to 87.0% after i.d. and i.m. vaccination, respectively. Seroprotection rates for the A strains A/Solomon Islands and A/Wisconsin were generally higher compared to the B/Malaysia strain and ranged from 89.1 to 98.2% across the i.d. groups. Similar rates of 96.3% for the A/Solomon Islands and 94.4% for the A/Wisconsin strain were observed in the i.m. group. Seroprotection rates for the B/Malaysia strain were 65.5, 83.0 and 72.7% after i.d. administration of 3.0, 4.5, and 6.0 microg HA of each strain, respectively, compared to a seroprotection rate of 85.2% in the i.m. group. In addition, marked increases in geometric mean titer (GMT) were observed across the groups for all influenza virus strains ranging from 6.9 to 70.5 for i.d. and from 16.9 to 56.5 for i.m. antigen delivery. Both routes of administration were well tolerated. Systemic reactions were broadly similar across the groups. With respect to local reactions the frequency of injection site pain and ecchymosis were significantly lower following i.d. vaccination, while other local reactions such as erythema occurred at higher rates with i.d. than with i.m. vaccine administration, as expected due to the mechanism of action for the i.d. route. The virosomal adjuvanted influenza vaccine (Inflexal V) was shown to be overall highly immunogenic and well tolerated when given i.d. at reduced doses to healthy adults, eliciting an immune response similar to that observed with full dose i.m. administration and thus suggesting a promising antigen-sparing strategy for universal influenza vaccination against endemic influenza. ISRCTN registry number: 33950739.
    Vaccine 06/2009; 27(27):3561-7. · 3.49 Impact Factor
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    ABSTRACT: Since the introduction to the Swiss market in 1997, Crucell (former Berna Biotech Ltd.), has sold over 41 million doses worldwide of the virosomal adjuvanted influenza vaccine, Inflexal V. Since 1992, 29 company sponsored clinical studies investigating the efficacy and safety of Inflexal V have been completed in which 3920 subjects participated. During its decade on the market, Inflexal V has shown an excellent tolerability profile due to its biocompatibility and purity. The vaccine contains no thiomersal or formaldehyde and its purity is reflected in the low ovalbumin content. By mimicking natural infection, the vaccine is highly efficacious. Inflexal V is the only adjuvanted influenza vaccine licensed for all age groups and shows a good immunogenicity in both healthy and immunocompromised elderly, adults and children. This review presents and discusses the experience with Inflexal V during the past decade.
    Vaccine 06/2009; 27(33):4381-7. · 3.77 Impact Factor
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    ABSTRACT: A post-marketing study was conducted in 26 paediatric practices in Germany to collect safety information on the virosomal adjuvanted influenza vaccine Inflexal® V (in Germany marketed as Infectovac Flu®). Children aged 6 months to 6 years received one or two doses. Adverse events were documented by parents/legal guardians in a questionnaire for four days after vaccination. The rates of adverse events were low: 14% of vaccine exposures were associated with systemic and 25% with local adverse events. Most symptoms were mild to moderate and resolved within a few days. Nearly 100% of parents/legal guardians would agree to have their child vaccinated again with Inflexal® V. Vaccination with Inflexal® V was safe, well tolerated and highly accepted by parents/legal guardians.
    Vaccine. 01/2009;
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    ABSTRACT: Measles virus (MV) has shown promise as an oncolytic virus in the treatment of different tumor models for human B-cell lymphoma, multiple myeloma, ovarian cancer, and glioma. We have shown that, in a phase I clinical trial, MV vaccine induces tumor regression in cutaneous T-cell lymphoma (CTCL) patients. Here, we investigated in detail, the effect of recombinant MV (rMV) vaccine strain in CTCL cell cultures, and in vivo in established CTCL xenografts in nude mice. The susceptibility of three CTCL cell lines, originating from patients, to rMV was tested by determination of cell surface expression of MV receptors. All cell lines expressed the receptors CD150 and CD46 and were easily infected by rMV and induced complete cell lysis. The cytoreductive activity was apparent in cells forming aggregates, indicating a cell-to-cell spread of MV and cytolysis owing to virus infection. Intratumoral (i.t.) injection of rMV, expressing enhanced green fluorescent protein induced complete regression of large established human CTCL tumors in nude mice, whereas tumors with control treatment progressed exponentially. Immunohistochemical analysis of tumor biopsies, after i.t. treatment, for MV-NP protein complex demonstrated replication of MV within the tumors. The data demonstrate the potential of MV as a therapeutic agent against CTCL.
    Journal of Investigative Dermatology 12/2006; 126(11):2525-32. · 6.19 Impact Factor
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    ABSTRACT: Some cutaneous T-cell lymphomas, (CTCLs) clonal T cells are deficient in interferon signaling, making them promising targets for viral oncolysis. We evaluated cytopathic effects of measles virus (MV) in CTCL. CTCL cell lines and infiltrating lymphocytes in CTCL expressed MV receptors CD150 and CD46. In a phase 1 dose escalation trial a total of 16 injections of live MV, Edmonston-Zagreb vaccine strain, were given intratumorally to 5 patients with CTCL. Patients had antimeasles-serum antibodies and were pretreated with interferon-alpha to prevent uncontrolled virus spread. The well-tolerated treatment with MV resulted in clinical responses. Evaluation of biopsies, before and at 11 days after injection, by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated local viral activity with positive staining for MV nucleoprotein (NP), an increase of the interferon gamma (IFN-gamma)/CD4 and IFN-gamma/CD8 mRNA ratios and a reduced CD4/CD8 ratio. All patients demonstrated an increased antimeasles antibody titer after therapy. The data demonstrate that CTCLs are promising targets for an MV-based oncolytic therapy.
    Blood 11/2005; 106(7):2287-94. · 9.78 Impact Factor
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    ABSTRACT: Transmissible spongiform encephalopathies often are caused by peripheral uptake of infectious prions, and the peripheral nervous system is involved in prion spread to the brain. Although the cellular prion protein is subjected to fast axonal transport, the mechanism of intranerval transport of infectious prions is unclear. Here we administered prions intranervally to transgenic mice overexpressing the four-repeat human tau protein, which exhibit defective fast axonal transport. These mice showed unaltered neuroinvasion, suggesting that transport mechanisms distinct from fast axonal transport effect prion neuroinvasion along peripheral nerves. Surprisingly, scrapie-sick tau transgenic mice accumulated intraneuronal deposits of hyperphosphorylated tau protein. The coincidence of tau and prion pathology resembled Gerstmann-Sträussler-Scheinker syndrome. These findings identify tau pathology as a possible end stretch of prion-induced neurodegeneration.
    Journal of Neuroscience 10/2002; 22(17):7471-7. · 6.91 Impact Factor
  • Valérie. Künzi
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    ABSTRACT: Diss. Naturwiss. Bern. Literaturverz. Universität, Bern

Publication Stats

176 Citations
30.13 Total Impact Points

Institutions

  • 2009
    • AVACO AG, Switzerland
      Basel-Landschaft, Switzerland
  • 2006
    • LKC Switzerland Ltd.
      Basel-Landschaft, Switzerland
  • 2002
    • University of Zurich
      • Institut für Neuropathologie
      Zürich, ZH, Switzerland