Infectious diseases encompass conditions caused by bacterial, viral or parasitic agents, from chronic infections to emerging threats such as COVID-19. Research here combines an understanding of the mechanisms of infection, the study of the host immune response and prevention strategies, in a context of rising antimicrobial resistance.
The work to which Inovarion has contributed in this field is organised around two groups. The first concerns antiviral immunity and immune memory. Inovarion took part in studying the maturation and persistence of the memory B-cell response against SARS-CoV-2[6], as well as in analysing messenger-RNA vaccination and its ability to recognise viral variants[5]. Other work addresses very-long-term B-cell memory against smallpox[4], or a recombinant viral vector (rAAV) targeting the skin to induce resident-memory CD8 T cells[8]. These studies describe in detail germinal-centre formation, somatic hypermutation and cross-reactivity between betacoronaviruses, offering a fine-grained reading of the quality and durability of protective immunity.
The second group concerns respiratory infections in cystic fibrosis. Inovarion has contributed to identifying the risk factors for acquisition and chronic airway colonisation by Pseudomonas aeruginosa (whose establishment marks a prognostic turning point in the disease)[3], to a genome-wide association study (GWAS) of susceptibility to this infection[1], and to analysing the seasonal and climatic influence on respiratory infections, taking into account the microbial ecology of the airways (Staphylococcus aureus, Aspergillus, Achromobacter)[2]. Added to this is translational bacteriology work on the adherent-invasive Escherichia coli strain associated with Crohn’s disease, and on its antibiotic tolerance within macrophages. An induced pluripotent stem cell line was also generated from a patient carrying a STING gene mutation, a model of a type I interferon-mediated auto-inflammatory vasculopathy[7].
This research mobilises single-cell sequencing (single-cell RNA-seq), antibody repertoire analysis, viral neutralisation assays and biolayer interferometry, genome-wide association studies and Mendelian randomisation, as well as epidemiological models (Cox models, Kaplan-Meier curves). This work has appeared in journals such as Cell, Immunity, European Respiratory Journal and the Journal of Cystic Fibrosis.
Immunology of infection, genetics of susceptibility, epidemiological modelling: Inovarion places this expertise at its partners’ service, from the laboratory to the clinical cohort.
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Representative publications
- Lin et al. Genome-wide association study of susceptibility to Pseudomonas aeruginosa infection in cystic fibrosis. Eur Respir J, 2024. Record → · PubMed
- Mésinèle et al. Seasonal and climatic influence on respiratory infections in children with cystic fibrosis. Scientific Reports, 2024. Record → · PubMed
- Mésinèle et al. Airway infections as a risk factor for Pseudomonas aeruginosa acquisition and chronic colonisation in children with cystic fibrosis. J Cyst Fibros, 2023. Record → · PubMed
- Chappert et al. Human anti-smallpox long-lived memory B cells are defined by dynamic interactions in the splenic niche and long-lasting germinal center imprinting. Immunity, 2022. Record → · PubMed
- Sokal et al. mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants. Immunity, 2021. Record → · PubMed
- Sokal et al. Maturation and persistence of the anti-SARS-CoV-2 memory B cell response. Cell, 2021. Record → · PubMed
- Barnabei et al. Generation of an iPSC line (IMAGINi011-A) from a patient carrying a STING mutation. Stem Cell Res, 2021. Record → · PubMed
- Gross et al. Cross-Presentation of Skin-Targeted Recombinant Adeno-associated Virus 2/1 Transgene Induces Potent Resident Memory CD8(+) T Cell Responses. J Virol, 2019. Record → · PubMed