Author:
Tabynov Kairat,Solomadin Maxim,Turebekov Nurkeldi,Babayeva Meruert,Fomin Gleb,Yadagiri Ganesh,Sankar Renu,Yerubayev Toktassyn,Yespolov Tlektes,Petrovsky Nikolai,Renukaradhya Gourapura J,Tabynov Kaissar
Abstract
Abstract
Given the ongoing COVID-19 pandemic and the need to build sustainable herd immunity in the population, the search for novel and safe vaccines for easy mass vaccination is an urgent task. We developed a novel intranasal subunit vaccine called NARUVAX-C19/Nano which is based on the SARS-CoV-2 spike protein receptor-binding domain (RBD) entrapped in mannose-conjugated chitosan nanoparticles (NP). To potentiate the cell mediated cell immune responses by the NP-vaccine formulation included the adjuvant CpG55.2, a toll-like receptor 9 agonist. The vaccine candidates administered intranasal were assessed for immunogenicity, protective efficacy, and virus transmission from vaccinates in inmates. The results were compared with a soluble RBD mixed with alum adjuvant vaccine administered intramuscular. In BALB/c mice administered with both the NP vaccines intranasal twice induced secretory IgA antibodies and pronounced Th1-cell responses, that was absent in intramuscular alum-adjuvanted RBD vaccine group. In Syrian hamsters delivered with similar NP formulations provided protection against a wild-type SARS-CoV-2 (D614G) challenge infection, indicated by significantly rescue in weight loss, reduced viral load in respiratory organs and lung pathology. However, despite significantly reduced viral load in the nasal turbinates and oropharyngeal swabs in NP vaccinated hamsters the virus transmission to naïve sentinel animals could not be blocked. In conclusion, intranasal delivered RBD-based NP vaccine formulations induced mucosal immune responses in mice and protected Syrian hamsters against SARS-CoV-2 infection. These findings are encouraging and supportive for further investigations to develop an intranasal NP-based vaccine platform to mitigate SARS-CoV-2 infection.
Publisher
Research Square Platform LLC
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