The aim of the project is to characterize replication-deficient pandemic influenza vaccine candidates (H5N1) in clinical and preclinical studies. 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 an d adaptive immunity.
Several standardized immunological techniques such as hemagglutination 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 hemagglutinin (HA) and neuraminidase (NA). Protective properties of the vaccine against homologous and heterologous influenza strains will be tested in ferret challenge experiments using dif ferent 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.
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