The purpose of this phase I/II trial is to evaluate safety and tolerability of a single dose of GHB16L2 administered by liquid nasal spray for vaccination against seasonal influenza virus infection. It is also performed to assess immunogenicity and pharmacokinetics (shedding).

开始日期2011-01-01

申办/合作机构

Avir Green Hills Biotechnology AG

NCT01078701 / Completed临床2期

Randomised, Double-blind, Placebo-controlled, Phase IIa Dose Finding Study of Single Dose GHB11L1 in Healthy Adults

The purpose of this phase IIa trial is to evaluate the immunogenicity of a single dose of GHB11L1 administered by liquid nasal spray for vaccination against influenza A (H1N1) virus.
This study is also performed to assess safety, tolerability and pharmacokinetics (shedding) of a single dose of GHB11L1 administered by liquid nasal spray.

开始日期2009-12-01

申办/合作机构

Avir Green Hills Biotechnology AG

NCT03745274 / Completed临床1期

Randomised, Double-blind, Placebo-controlled, Phase I Dose- Escalation Study of Two Doses GHB04L1 in Healthy Adults

This study evaluates safety, tolerability and immunogenicity of two doses of GHB04L1, a liquid formulation of the replication- deficient influenza A/Vietnam/1203/04(H5N1)-like ∆NS1 virus in healthy adults. Subjects are randomised at a ratio of 2:1 for GHB04L1 (6.8 log10 or 7.5 log10 TCID50/dose/volunteer) or placebo.

开始日期2008-12-19

申办/合作机构

Avir Green Hills Biotechnology AG

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0 项与 Avir Green Hills Biotechnology AG 相关的专利（医药）

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2019-06-01·Vaccine3区 · 医学

Safety and immunogenicity of a replication-deficient H5N1 influenza virus vaccine lacking NS1

3区 · 医学

Article

作者: Kiselev, Oleg ; Seipelt, Joachim ; Nicolodi, Christina ; Wolschek, Markus ; Groiss, Franz ; Muster, Thomas

BACKGROUNDTraditional inactivated influenza vaccines are the type of vaccines that were most frequently developed for immunization against the highly pathogenic avian H5N1 influenza virus. However, clinical trials with inactivated influenza vaccines for H5N1 indicated that high doses and at least two immunizations are required for an effective immune response (Nicholson et al., 2001; Treanor, Campbell et al., 2006; Treanor, Schiff et al., 2006; Ehrlich et al., 2008). We investigated the safety and immunogenicity of a live attenuated H5N1 vaccine (delNS1-H5N1) lacking the interferon antagonist nonstructural protein 1 (NS1).METHODSWe conducted a double-blind, placebo-controlled, phase 1 study in healthy adult participants who were randomly assigned at a 2:1 ratio to receive two immunizations of delNS1-H5N1 vaccine at 6.8 log10 50% tissue culture infectious doses (TCID₅₀)/subject or 7.5 log10 TCID₅₀/subject, or placebo.RESULTSIntranasal vaccination with the live attenuated delNS1-H5N1 vaccine was safe and well tolerated. The most common adverse events identified were symptoms associated with mild influenza infections, such as increased body temperature (>37.0 °C), pharyngeal erythema, rhinitis and throat irritation, and were reported within 7 days after the first immunization. delNS1-H5N1 was able to induce significant vaccine-specific serum antibody titers even at the lower dose level of 6.8 log10 TCID₅₀/subject. Seroconversion occurred in 75% of study participants after only one immunization with 7.5 log10 TCID₅₀/subject. Vaccine-specific local IgA responses were observed in 41.7% of individuals that showed serum antibody responses after 2nd immunization.CONCLUSIONSWe show that vaccination with a live attenuated H5N1 influenza vaccine lacking NS1 is safe and induces significant levels of vaccine-specific antibodies even after one immunization. The safety and immunogenicity data indicate that delNS1-H5N1 has the potential to fulfil the unmet need for an effective influenza vaccine in pandemic situations. (ClinicalTrials.gov identifier NCT03745274).

2017-12-01·Molecular Therapy - Oncolytics

Targeting an Oncolytic Influenza A Virus to Tumor Tissue by Elastase

Article

作者: Egorov, Andrej ; Kuznetsova, Irina ; Garay, Tamas ; Pisareva, Maria ; Pleschka, Stephan ; Bergmann, Michael ; Stukova, Marina ; Arnold, Tobias ; Hegedus, Balazs ; Schwager, Cornelia ; Aschacher, Thomas

Oncolytic viruses are currently established as a novel type of immunotherapy. The challenge is to safely target oncolytic viruses to tumors. Previously, we have generated influenza A viruses (IAVs) containing deletions in the viral interferon antagonist. Those deletions have attenuated the virus in normal tissue but allowed replication in tumor cells. IAV entry is mediated by hemagglutinin (HA), which needs to be activated by a serine protease, for example, through trypsin. To further target the IAV to tumors, we have changed the trypsin cleavage site to an elastase cleavage site. We chose this cleavage site because elastase is expressed in the tumor microenvironment. Moreover, the exchange of the cleavage site previously has been shown to attenuate viral growth in lungs. Newly generated elastase-activated influenza viruses (AE viruses) grew to similar titers in tumor cells as the trypsin-activated counterparts (AT viruses). Intratumoral injection of AE viruses into syngeneic B16f1 melanoma-derived tumors in mice reduced tumor growth similar to AT viruses and had a better therapeutic effect in heterologous human PANC-1-derived tumors. Therefore, the introduction of the attenuation marker "elastase cleavage site" in viral HA allows for safe, effective oncolytic virus therapy.

2015-10-01·Archives of Virology4区 · 医学

A genetically adjuvanted influenza B virus vector increases immunogenicity and protective efficacy in mice

4区 · 医学

Article

作者: Kittel, Christian ; Shurygina, Anna Polina ; Kiselev, Oleg ; Romanovskaya-Romanko, Ekatherina ; Stukova, Marina ; Wolschek, Markus ; Romanova, Julia ; Egorov, Andrej ; Wressnigg, Nina ; Muster, Thomas

The existence of multiple antigenically distinct types and subtypes of influenza viruses allows the construction of a multivalent vector system for the mucosal delivery of foreign sequences. Influenza A viruses have been exploited successfully for the expression of extraneous antigens as well as immunostimulatory molecules. In this study, we describe the development of an influenza B virus vector whose functional part of the interferon antagonist NS1 was replaced by human interleukin 2 (IL2) as a genetic adjuvant. We demonstrate that IL2 expressed by this viral vector displays immune adjuvant activity in immunized mice. Animals vaccinated with the IL2 viral vector showed an increased hemagglutination inhibition antibody response and higher protective efficacy after challenge with a wild-type influenza B virus when compared to mice vaccinated with a control virus. Our results demonstrate that it is feasible to construct influenza B vaccine strains expressing immune-potentiating foreign sequences from the NS genomic segment. Based on these data, it is now hypothetically possible to create a trivalent (or quadrivalent) live attenuated influenza vaccine in which each component expresses a selected genetic adjuvant with tailored expression levels.

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