Intracellular Carrier Against Resistant microOrganisms (ICARO)

Project Information

ICARO

Grant agreement ID: 101046927

DOI

10.3030/101046927

EC signature date 24 March 2022

Start date 1 April 2022

End date 30 September 2026

Funded under

• The European Innovation Council (EIC)

Total cost

€ 2 997 047,00

EU contribution

€ 2 997 047,00

Coordinated by

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Spain

Periodic Reporting for period 2 - ICARO (Intracellular Carrier Against Resistant microOrganisms (ICARO))

Reporting period: 2023-04-01 to 2024-09-30

Summary of the context and overall objectives of the project

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, the lack of effective antivirals and the growing scenario of antibiotic rresistance 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 already been 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 a long period of time in the cell. Our vision is to develop silicon microchips to cross the cellular barriers carrying antigens for their presentation.

By achieving that, ICARO might be a ground-breaking new vaccination strategy to boost T cell responses by rapidly scouting a repertoire of antigens for a given pathogen. We aim to develop standardized methods for ICARO manufacturing and functionalisation that are easily applicable to other pathogens, thus accelerating the generation of new vaccines in the future.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the second reporting period, the main tasks of the ICARO project has been focused on demonstrating ICARO bio-chips, functionalized with entire pathogens, inducing an immune response in cells, and boosting the activation of specific lymphocytes. Lack of toxicity has been assessed in-vivo and first assays to explore the protective effects of ICARO bio-chips in mice were launched. Besides that, as the first step for scaling-up the production, the chemistry for pathogen immobilization has been improved to achieve a unique reaction suitable for all the models used (virus, parasites, and bacteria). Finally, the patentability study was updated, and a new regulatory pathway and business plan were established, taking into account future market barriers and main competitors in the field.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

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.