Bioengineering tools to speed up the discovery and preclinical testing of vaccines for SARS-CoV-2 and therapeutic agents for COVID-19

Manuela Teresa Raimondi1, Francesca Donnaloja1, Bianca Barzaghini1, Alberto Bocconi1, Claudio Conci1, Valentina Parodi1, Emanuela Jacchetti1, Stephana Carelli2 1 Department of Chemistry, Materials and Chemical Engineering G. Natta, Politecnico di Milano, Milano, Italy 2 Pediatric Clinical Research Center “Fondazione Romeo ed Enrica Invernizzi”, Department of Biomedical and Clinical Sciences L. Sacco, University of Milano, Italy

We would like to update the international research community on the cell modeling tools in 3D, already used in virology and vaccinology, that could accelerate the understanding of SARS-CoV-2 infection mechanisms and could speed up the development of relevant vaccines and therapeutic agents against COVID-19.

Cell morphology, virus penetration and cell damage are replicated similarly to in-vivo in 3D cell and organoid static culture models, which are impressively more permissive to viral infection than cell monolayers: cell expression of viruses receptors, antiviral genes, antigens to viruses and inflammatory markers is more similar, in time and space, to in-vivo. Moreover, in 3D models, the sensitivity to antiviral drugs is significantly lower and highly comparable to in vivo conditions.

Perfused cell models allow to extend infection studies even up to several months, on stable cell cultures of highly differentiated cells, at higher infection efficiency and at lower multiplicity of infection, compared to non-perfused models. This potentially enables to extend to in vitro systems the study of the life cycle and genetic stability of new viruses like SARS-CoV-2, even if derived in minimal doses from patients, and also to test sequential antiviral drug treatments.

Most importantly, perfused cell models allow to reproduce dynamic interactions between tissue-resident cells and circulating ones, including the response to pathogens of innate and adaptive lymphocytes, thus, to extend to in vitro some aspects of vaccines testing.

Describe funding body that supported the work

This research has received funding from: the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (G.A. No. 646990 – NICHOID, No. 754467 -NICHOIDS and No. 825159 – MOAB); the Italian Ministry of University and Research (MIUR) under the grant program MIUR-FARE-2016 (G.A. No. R16ZNN2R9K – BEYOND); the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) under the CleanCut 2020 Challenge (G.A. No. NC/C01903/1 – MOAB).

Describe conflict of interest (if any)

MTR is a co-founder of a university spin-off company, MOAB S.r.l., and holds shares.