Towards a new nanoparticle vaccine technology. Rational design of pathogen-mimicking nanoparticles for controlled immunostimulation.

Traditional vaccination methods, consisting of live-attenuated or heat-killed pathogens administered to healthy individuals, have been highly successful in preventing and eradicating global diseases (including smallpox and poliomyelitis). However, preventive vaccination still remains elusive for many other diseases (including malaria, tuberculosis and HIV). Therapeutic vaccines, i.e. designed to cure patients who are already infected or ill, have shown promising results against cancer, autoimmune diseases, as well as HIV, tuberculosis and hepatitis, although none of them are yet recognized as efficacious therapy in humans. Therefore, new vaccination strategies, based on a growing understanding of the immune activation mechanisms, are needed.The proposed study focuses on novel nanoparticle vaccines, based on a versatile and robust approach for producing nanomaterials composed of solid core of well defined physicochemical properties and a hydrophilic, immune-stimulating polymeric shell. Combining recent advances in nanotechnology with the requirements of novel vaccine design, this technology will allow the generation of new pathogen-mimicking nanoparticles, designed for specific antigen delivery and controlled immunostimulation.The core material properties will define the nanoparticle size, in vitro and in vivo traceability, degradability. The nanoparticle size can be varied to resemble that of a particular virus and, as recent studies revealed, size is a fundamental variable which affects a) the way nanoparticles (and viruses) enter cells and influence the cell functions, and b) the final vaccine localization and targeting, either in the peripheral tissue or in lymph nodes. The functional polymeric shell will be designed to incorporate the right sequence of chemical groups (saccharides, hydroxyl groups) which activate the innate immune system, as well as antigens to be displaced to the Antigen Presenting Cells. This new vaccine technology will be able to elicit the appropriate immune response, by combining an efficient antigen presentation with adjuvant functions, for a more specific immune regulation and less non-specific (adverse) immune activation.

This research has a threefold impact: - Nanoscience: the constructs studied in this project will allow the advancement of knowledge regarding the development of simple, versatile and robust synthetic routes for the preparation of novel functional bioactive nanomaterials. - Immunology: the new technology is particularly relevant for understanding fundamental phenomena involved in the activation of immune cells and in antigen presentation mechanisms which trigger the adaptive immune response. - Vaccine research: our results will impact mostly on the community involved in vaccine development against major global diseases. Reaching these different communities, while keeping a contact to the biomaterials area, where we originally belong, is an issue that will require a capillary dissemination of results through publications in high impact journals and presentations at international conferences. However, we will specifically target national meetings and workshops, in order to forge a network of possible end-users that will contribute to the validation and improvement of the new materials. National and possibly also international academic or industrial collaborations will allow knowledge exchange and the identification of new targets in vaccine development. It is likely that protectable IP will be generated, both from this project directly and from possible spin-outs, in the areas of nanotechnology and vaccine design. The PI's Research Group works in association with the Organic Materials Innovation Centre (OMIC) and The Knowledge Centre for Materials Chemistry (KCMC) for materials characterisation. The centres will provide strategic links with industry for the advancement of this technology. Moreover, the project will benefit from the Group's partnership with the Manchester Integrating Medicine & Innovative Technology (MIMIT), which will facilitate collaborations between clinicians, scientists, engineers and industry to develop innovative technology for patient benefit.