We hypothesize that capsules mimicking the size, shape and surface properties of bacteria can be used to deceive the immune system, making the body believe that we are administering the pathogens themselves to trigger an effective protective immune response (both humoral and cellular). We have selected as a proof-of-concept infections caused by S. aureus but a priori this universal approach can be used where traditional vaccines have not been able to effectively prevent the advance of a large number of infectious pathologies or to prevent the growth and action of antimicrobial multiresistant (AMR) bacteria. Both are major health challenges that the worldwide society is facing nowadays.
The capsules with an ellipsoidal shape will be done from polyurethane and PLGA using a double emulsion process. To shape the nanocapsules (~500 nm x~700 nm) they will be included in a PVA film, dried and mechanically stretched until the desired shape is achieved. Finally, the film is dissolved and the capsules that maintain the shape are released. The fabrication process also allows us to efficiently encapsulate an active species such as an adjuvant agent, a fluorophore or DNA. In a step further, the capsules will be coated with the antigens of the pathogen itself, so that it interacts with the immune system of the host organism. Finally, a screening of in vivo toxicology will be performed in the invertebrate model of Galleria mellonela and from there best candidate will be evaluated in vivo in mice by analysing their immunoreactivity and immune response triggering.
Multidisciplinarity within BioVac
This project is a combined effort of two complementary groups, each one of them well-recognized in the area of expertise. The first is the Nanostructured Functional Materials (NANOSFUN-ICN2) group, which has a broad and longstanding experience in the synthesis, characterization and encapsulation with micro-/nanocapsules and in the manufacture of novel materials for the industry based on biocompatible coatings. The second, the group of Dr. Eduard Torrents from the Bacterial infection and antimicrobial therapy group, is a world reference in the development of new strategies to combat bacterial infections, via development of artificial cells and biomimetic cell components in order to use these materials to prevent and treat infectious diseases.
How can such complementarity be managed? In the first stage, the nanocapsules will be obtained and characterized at the ICN2. Once isolated, the same group will functionalize them with the antigens kindly provided from our colleague at Hong Kong, Prof. JD Huang. Finally, the amount of antigen added to the surface will be characterized and the surface properly modified, if needed, to ensure a stable colloidal dispersion easy to be manipulated. Afterwards, the samples will be taken by the group at IBEC to perform all the in vitro and in vivo characterization. In addition to frequent chats and exchange of ideas and results between both labs via skype or face-to-face thanks to the proximity of both centres, we also expect the PhD student to actively participate in all three work packages, acting as a link between the two groups.
More information about BioVac, including an updated abstract as of January 2020 can be downloaded below: