Novel nasal virosome spray vaccine to protect against COVID-19

Tiziana Patrizia Cremona, Burak Vedat Ozan,Melanie Scalise,Melanie Scherer,Seyran Mutlu, Anna Barbara Tschirren, Farien Bhoelan, Denzel Bemelman,Philippe Plattet, Toon Stegmann,Thomas Geiser, Sylvain Fleury,Amiq Gazdhar

Airway cell biology and immunopathology(2022)

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摘要
Intramuscular COVID-19 vaccines protect, but do not prevent transmission. We developed a nasal vaccine that can be stored at ≥ +4°C and with the aim to induce better upper respiratory tract mucosal immunity, particularly in the nasal cavity to interfere more efficiently with the primary SARS-CoV-2 site of replication. In this study, we focus on tolerance for and the immunogenicity of a thermostable intranasal powder vaccine, containing the Receptor Binding Domain (RBD) of the spike protein of SARS-CoV-2 integrated into the lipid membrane of virosomal nanoparticles. Female and male Wistar rats were immunized with a dry intranasal powder vaccine containing recombinant RBD, administered twice to rats at days 0 and 21. Serum samples were collected at different time points. At the end of the study, bronchoalveolar lavage fluid, nasal washes, lymph nodes, spleen, and lung were collected for analysis. A group of rats of matched age and gender was used as a control. Humoral and cellular immune responses were characterized. Intranasally immunized rats showed no adverse effects related to the local application. Specific anti-RBD antibody response was detected in serum, bronchoalveolar lavage, and nasal wash samples. The neutralizing capacity of serum samples was shown in neutralization assay with pseudovirus particles. RBD-specific T cell responses were observed in lymph nodes, lungs, and bronchoalveolar fluid, and the immune cell populations were characterized. The results obtained encourage further evaluation of this intranasal vaccine candidate for preventing lung disease complications, but also for preventing intranasal virus acquisition and for reducing virus shedding to reduce the virus community transmission.
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