Human nasal epithelium is the initial site of infection and the first defense barrier during influenza (Flu) virus infection. We challenged the MucilAir™-pool, an in vitro human nasal epithelium model cultured at the air liquid interface, with H1N1 Flu virus and nasal Flu vaccine Fluenz Tetra® (AstraZeneca), a live attenuated vaccine based on four Flu strains: two A/strains (H1N1, H3N2) and two B/strains (Austria, Phuket). Moreover, the anti-SARSCoV-2 mRNA-based vaccine Comirnaty (Pfizer-BioNTech) was also tested on the MucilAir™-pool to evaluate whether a lipid nanoparticles and mRNA-based vaccine was tolerated by nasal epithelium and may constitute a platform for future nasal vaccines. Nasal epithelial integrity was assessed by measuring transepithelial electrical resistance (TEER). Results highlighted a statistically significant decrease of TEER after 48 and 72 hours (h) of H1N1 infection and stimulation with highest doses of Flu vaccine. Next, by evaluating lactate dehydrogenase (LDH) release, a considerable cytotoxic effect was observed only after 72h H1N1 infection, whereas Flu vaccine stimulation drove a time- and dose-dependent cytotoxic effect starting from 24h and peaking at 72h of exposure. Also ciliary function, determined by microscopic recording and image analysis, was affected by high Flu vaccine doses. Interestingly, also a dose- and time-dependent modulation of different cytokines, chemokines and anti-viral transcription was found. Although formulated for intramuscular administration, Comirnaty vaccine resulted well tolerated by the MucilAir™-pool model. Indeed, no significant differences were observed in cytotoxicity, tissue integrity and ciliary function. Our data indicate that the MucilAir™-pool is a robust platform to test different vaccine formulations not only for toxicity evaluation but also to assess nasal epithelium ability to address immune cell activation. Funded by Italian Ministry of Health (RIPrEI project, L106/2021), Swiss State Secretariat for Education, Research and Innovation (SERI) and European Union’s Horizon Europe research and innovation programme (NOSEVAC project. Grant N°101080528
FLU signature in nasal epithelium: from infection to nasal vaccination / Ricci, Daniela; Barbin, Guy; Paola Etna, Marilena; Severa, Martina; Horckmans, Anaïs; Cairo, Giada; Boda, Bernadett; Marina Coccia, Eliana; Constant, Samuel. - (2024). (Intervento presentato al convegno LIVe 2024 Lung in vitro eventfor innovative and predictive models tenutosi a Nice, France).
FLU signature in nasal epithelium: from infection to nasal vaccination
Daniela Ricci;Giada Cairo;
2024
Abstract
Human nasal epithelium is the initial site of infection and the first defense barrier during influenza (Flu) virus infection. We challenged the MucilAir™-pool, an in vitro human nasal epithelium model cultured at the air liquid interface, with H1N1 Flu virus and nasal Flu vaccine Fluenz Tetra® (AstraZeneca), a live attenuated vaccine based on four Flu strains: two A/strains (H1N1, H3N2) and two B/strains (Austria, Phuket). Moreover, the anti-SARSCoV-2 mRNA-based vaccine Comirnaty (Pfizer-BioNTech) was also tested on the MucilAir™-pool to evaluate whether a lipid nanoparticles and mRNA-based vaccine was tolerated by nasal epithelium and may constitute a platform for future nasal vaccines. Nasal epithelial integrity was assessed by measuring transepithelial electrical resistance (TEER). Results highlighted a statistically significant decrease of TEER after 48 and 72 hours (h) of H1N1 infection and stimulation with highest doses of Flu vaccine. Next, by evaluating lactate dehydrogenase (LDH) release, a considerable cytotoxic effect was observed only after 72h H1N1 infection, whereas Flu vaccine stimulation drove a time- and dose-dependent cytotoxic effect starting from 24h and peaking at 72h of exposure. Also ciliary function, determined by microscopic recording and image analysis, was affected by high Flu vaccine doses. Interestingly, also a dose- and time-dependent modulation of different cytokines, chemokines and anti-viral transcription was found. Although formulated for intramuscular administration, Comirnaty vaccine resulted well tolerated by the MucilAir™-pool model. Indeed, no significant differences were observed in cytotoxicity, tissue integrity and ciliary function. Our data indicate that the MucilAir™-pool is a robust platform to test different vaccine formulations not only for toxicity evaluation but also to assess nasal epithelium ability to address immune cell activation. Funded by Italian Ministry of Health (RIPrEI project, L106/2021), Swiss State Secretariat for Education, Research and Innovation (SERI) and European Union’s Horizon Europe research and innovation programme (NOSEVAC project. Grant N°101080528I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
