We have recently developed a novel type of vaccine platform, so-called self-assembling polypeptide nanoparticles (SAPNs). We have demonstrated that these SAPNs are highly immunogenic and induce a strong B cell immune response characterized by high antibody titers without the ned of adjuvant. We have engineered and biophysically characterized SAPNs to which activated nicotine hapten molecules can be coupled. Antibodies induced upon immunization with these SAPNs will bind nicotine in the blood stream and hence counteract the addiction-causing effect of nicotine. The overarching goal of the project is to demonstrate safety, tolerability and immunogenicity of the SAPN nicotine vaccine in a clinical trials phase I study. To achieve this goal we propose to first establish the immunogenicity of these nicotine-SAPNs in mice and to optimize their design with respect to the density of the hapten molecules, the SAPN concentration, and the route of immunization to obtain the highest possible antibody titer. Next, we will optimize the SAPNs for human use by engineering pan-DR binding epitopes that are specific for the human haplotypes into the SAPN scaffold. The immunogenicity of the SAPNs will then be verified in a second animal model followed by toxicity testings that will establish a safety profile of the SAPNs. The translation path will then include protein formulation and lyophilization studies to optimize the long-term storage properties of the SAPNs. Along with the application for Swissmedic approval for clinical studies we will work on a large-scale production protocol of the final vaccine. The vaccine of the present project is adjuvant-free. This will eliminate all adjuvant induced side effects and reduce the price as it will allow a simple galenic formulation of the vaccine. Since the SAPN-vaccines can be applied intranasally their patient acceptance is expected to be higher than for curent vaccine approaches which require painful intramuscular injections.
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