Development of Influenza del NS1 Virus as a Vector For Foreign Antigens
The project CHIMERIC VACCINES is being carried out by an international consortium over a 30-month period. The consortium aims at developing a novel vaccine that will provide protection against avian influenza and seasonal influenza. The technical basis is a replication deficient influenza virus that was modified to express foreign antigens.
CHIMERIC VACCINES is led by the Austrian SME Green Hills Biotechnology and consists of three partner companies in Austria, Slovenia and the Czech Republic and two renowned university partners in Austria and Germany. In order to bring these vaccines to clinical use, one of the partners is the Russian WHO reference laboratory for influenza in St Petersburg, which has abundant experience in testing new vaccines.
Avian influenza is an infectious disease of birds caused by type A strains of the influenza virus. The disease occurs worldwide. While all birds are thought to be susceptible to infection with avian influenza viruses, many wild bird species carry these viruses with no apparent signs of harm. A highly pathogenic form was first identified in Italy in 1878 and can lead to a mortality rate in infected animals of 100% within 48 hours.
Influenza viruses are species-specific and only rarely cause infection in other species. Since 1959, instances of human infection with an avian influenza virus have been documented on only 10 occasions. Of the hundreds of strains of avian influenza A viruses, only four are known to have caused human infections: H5N1, H7N3, H7N7 and H9N2. In general, human infection with these viruses has resulted in mild symptoms and very little severe illness, with one notable exception - the highly pathogenic H5N1 virus.
Currently, the H5N1 virus is of greatest significance as it has crossed the species barrier to infect humans on at least three occasions in recent years leading to the current outbreaks that began in December 2003. Currently, no vaccine against avian influenza is available.[+] Read More
This consortium has developed a novel approach for vaccination against avian influenza. The technology is based on the insertion of selected epitopes into a genetically modified influenza virus that is apathogenic. To achieve these results, both a stable vector and promising antigens were identified. Antigen selection was based on bioinformatics methods that were substantiated by experimental validation. The properties of the backbone vector in terms of safety and stability were assessed in preclinical experiments and gave highly satisfactory results. To bring the proposed chimeric vaccine into clinical trials, a production process in small scale was established using a novel purification technology. Finally, preparations for a clinical trial in Russia were made by the Russian Institute of Influenza.
Results of this project will shed light on important aspects in the development of novel vaccination strategies and will help to further develop the concept of a chimeric vaccine. In addition, important information regarding immunogenicity and safety will be generated and a process for the production of purified viruses will be established.
The vaccine developed in this project will be an important step towards a vaccine that can induce an immune response against foreign antigens of pathogens. The technologies that are used in this project will have the potential to be applied to other relevant pathogens as well.