Novel FluVacc vaccine enters Phase I trial
influenza virus has started a Phase I clinical trial at the Medical
University of Vienna in Austria.
The study with 24 healthy volunteers at the University's Institute of Virology will test the safety of the FluVacc vaccine administered as a single immunisation. It will also analyse the body's response to FluVacc by detecting influenza virus-specific antibodies in the volunteers' blood and nasal secretions. Avir Green Hills Biotechnology (GHB), the Austrian company that is developing FluVacc in collaboration with five other companies and three academic institutions under the European Union's Sixth Framework Programme (FP6), believes the vaccine has safety, efficacy, ease-of-delivery and manufacturing advantages over both the traditional inactivated virus products that dominate the influenza vaccine market and other available vaccines based on live attenuated viruses. FluVacc is administered as an intranasal spray and manufactured in cultured Vero cells. These two characteristics distinguish it from conventional influenza vaccines, along with the Delta NS (delNS) viral engineering technology used to create FluVacc. This technology uses reverse genetics to produce a vaccine that, according to GHB, is highly immunogenic while being safely attenuated. It does this by deleting the pathogenicity factor NS1, so that the resulting vaccine strain "looks like a pathogenic influenza virus to the body but is unable to cause disease". Live attenuated-virus vaccines for influenza induce longer-lasting and more cross-protective immunity than conventional inactivated-virus vaccines, with significantly higher protection rates, GHB says. While the live attenuated viruses currently on the market have a good safety record, "shedding of the vaccine virus occurs and unexpected complications in young children, the elderly and immunocompromised people might arise from widespread use", it comments. The company has already shown FluVacc to be safe, immunogenic and protective against experimental challenge with wild-type virus in different animal models such as ferrets and macaque monkeys, it notes. FluVacc is given intranasally with a nebuliser instead of being injected into muscle. In addition to ease of administration, this approach stimulates a protective immune reaction directly at the site of the virus entry, GHB points out. The use of reverse genetics to engineer the vaccine allows for quick and efficient fine-tuning to circulating virus strains, the company says, adding: "This method is essential for attenuation of highly virulent avian influenza viruses and the timely distribution of candidate viruses in the case of a pandemic emergency". It claims similar advantages from manufacturing FluVacc in cultured Vero cells. GHB has developed a system involving automated production in bioreactors that can easily be scaled up to meet increased demand. Manufacturing of conventional influenza vaccines in embryonated chicken eggs can only be automated to a limited extent, the company points out. The technique depends on the availability of pathogen-free eggs, "which can be in short supply, especially during a pandemic". Another drawback is that vaccines produced in chicken eggs cannot be given to people with an egg allergy. GHB is developing FluVacc under the EU's Sixth Framework Programme as part of an international consortium including BIA Separations (Slovenia), Biotest (Czech Republic), GPC Biotech AG (Germany), Weikom & Network (Austria), the Medical University of Vienna, the Robert Koch Institute (Germany) and the Institute for Influenza (Russia). The project started in September 2005 and will be supported for five years with EU funding of €9.2m. The aim is to complete Phase I and II clinical trials with FluVacc by early 2009, after which GHB will seek further funding or a strategic alliance with a pharmaceutical company for Phase III. So far the Austrian company has amassed around €25m for product development in the form of venture capital, grants, silent participation capital and the founders' own funds. GHB has three other collaborative projects running under the Sixth Framework Programme: a combined vaccine for influenza/Severe Acute Respiratory Syndrome (SARS) involving the development of new biosafe virus vectors; an intranasal pandemic influenza vaccine against the H5N1 avian influenza virus; and chimeric vaccines based on the development of the influenza delNS1 virus as a vector for foreign antigens. The company is also developing OncoFlu, an anticancer based on a genetically engineered influenza virus that has shown selective anti-tumour effects in SCID mouse melanoma models; and MelVir, a tool for early diagnosis of melanoma based on GHB's finding that the condition is associated with the expression of endogenous retroviruses.
