Immumogenicity and Protective Efficacy of Intranasal DELNS1(H5N1) Influenza Vaccine
In collaboration with six partners in four European countries and in Russia, Green Hills Biotechnology is developing a novel vaccine against avian influenza, within the framework of a research project subsidised by the European Union. The project budget totals EUR 2.6 million.
This project is being carried out by an international consortium over a three-year period. Besides Green Hills Biotechnology, a total of three other companies and three universities are participating in the development and evaluation of an intranasal H5 vaccine. The proposed vaccine is based on proprietary technology from Green Hills Biotechnology. Immunological properties will be assessed by the Goethe University in Frankfurt and preclinical experiments will be carried out at Biotest s.r.o. in the Czech Republic. Novel, sensitive methods developed for assessment of the antibody response against viral proteins are being established in cooperation with the Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry in Moscow. These assays will allow the selection of an optimal vaccine candidate that will be subsequently evaluated in clinical trials at the Medical University, Vienna, and at Retroscreen in the UK.[+] Read More
Mankind is threatened by avian influenza. For the period of December 1, 2003, to February 3, 2006, the WHO reported 161 confirmed human cases of avian influenza A (H5N1); of these 86 (or 53%) were fatal. It is not clear how many amino acid substitutions are still needed to convert avian viruses into a new human pandemic strain. Old human influenza viruses of the H1N1 or H2N2 subtypes could also return in humans, causing a new pandemic. Sooner or later there will be an influenza pandemic unless new and more efficient vaccines are developed. Therefore, the current situation with the H5N1 avian flu could be considered as a challenge for global science and the biotech industry.
The main objective of the current project aims to define an intranasal H5N1 pandemic vaccine with enhanced capacity to evoke a strong, long lasting local and systemic immune response in humans. The replication-deficient vaccine is based on the deletion of the NS1 protein (DelNS1 vaccine). First, several vaccine candidates will be screened for parameters including antigenic properties, receptor specificity, attenuation and immunogenicity in animal models. Studies on elucidation of mechanisms responsible for protection will comprise parameters of innate and adaptive immunity. Several standardised immunological techniques such as haemagglutination inhibition (HI) and ELISA will be used for evaluation of vaccine candidates. In addition, novel sensitive methods based on synthetic sialic receptor analogues will be developed for assessment of the antibody response against the haemagglutinin (HA) and neuraminidase (NA).
Protective properties of the vaccine against homologous and heterologous influenza strains will be tested in ferret challenge experiments using different H5 strains. To close the gap between the ferret model and human studies we will use the macaque model to evaluate the immune response. These pre-clinical studies will allow the selection of the most potent vaccine candidate, which will be produced according to cGMP guidelines on Vero cells. After toxicological evaluation of the vaccine, clinical Phase I/II studies will be performed. If permitted by authorities, a human challenge study using attenuated H5 virus will be carried out. Alternatively, for proof of principle of the delNS technology, an H1-delNS1 vaccine will be produced and used in an H1 challenge study.
The proposed clinical evaluation of delNS1 (H5N1) vaccine should be considered as a component of European systemic efforts to prevent and control potential pandemics of avian influenza. This is a severe respiratory infection that poses a major health threat on a worldwide scale. The proposed vaccine will reduce mortality and morbidity rates, lost workdays, and hospitalisations in case of H5N1 outbreak.