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Intracellular Carrier Against Resistant microOrganisms (ICARO)

Periodic Reporting for period 1 - ICARO (Intracellular Carrier Against Resistant microOrganisms (ICARO))

Reporting period: 2022-04-01 to 2023-03-31

Vaccines have a history of success in the control of infectious diseases. The need for new efficient vaccination strategies is of particular significance due to the emergence of new pathogens, lack of effective antivirals and the growing scenario of antibiotic resistances. Intracellular pathogens and viruses are responsible for epidemics like tuberculosis, malaria, or COVID-19. T cells eliminate cells exposing antigens derived from intracellular pathogens via Major-Histocompatibility Complexes. This antigen-presentation pathway is often subverted by viruses or intravacuolar pathogens, for which the antigenic repertoire is greatly diminished.

ICARO take advantage of MEMS capabilities to obtain the proof-of-concept for a new generation of vaccines needed for diseases caused by intracellular pathogens (viruses, bacteria and protozoa) with a high societal impact. The biochips technology underlying this project has been already proven: biochips are optimal to reach and work in the intracellular environment: volume in the range of μm3, easy to manipulate, proven internalization by phagocytic and non-phagocytic cells and the ability to remain long period of time in the cell. Our vision is to develop silicon microchips that will cross the cellular barriers carrying antigens for its presentation.

By achieving that, ICARO might be a ground-breaking new vaccination strategy to boost T cells responses by a rapid scouting of a repertoire of antigens for a given pathogen. We aim to develop standardized methods for ICARO manufacturing and functionalisation to be easily applicable to other pathogens, thus accelerating the generation of new vaccines in the future.
During the first reporting period different ICARO-chip version have been designed and manufactured. In addition, several immobilization strategies have been tested for various pathogens with positive results. Initial in vitro test have been developed to better understand the ICARO chips performance in vitro.
ICARO proposes a completely novel, cutting-edge approach designed to improved current limitations in vaccination strategies. Our ground-breaking project is focused on the binding of entire inactivated pathogens to chips. The biochips technology underlying this project has been already proven: biochips are optimal to reach and work in the intracellular environment: volume in the range of μm3, easy to manipulate, proven internalization by phagocytic and non-phagocytic cells and the ability to remain long period of time in the cell. Our vision is to develop silicon microchips that will cross the cellular barriers carrying antigens for its presentation.
In order to realize the project impact, the consortium has already achieved initial promising results which show the feasibility of the chips manufacturing and the viability of different pathogen immobilization protocols as the first steps of our science-towards-technology effort. In addition, the consortium is starting to characterizing the internalization of the chips and how different sizes, geometries and type of chips may impact on the internalization of the loaded chips. In the following reporting periods, the consortium will answer the most relevant questions in the project, especially in vivo toxicity and efficacy. The consortium has confirmed the good perspectives for protecting a broad concept of the use of silicon-chips loaded with whole (or part of) pathogens as an immunization strategy in the context of infection.