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Characterization of stability, safety and immunogenicity of the mRNA lipid nanoparticle vaccine Iribovax® against COVID-19 in nonhuman primates.
- Source :
-
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2023 Aug; Vol. 360, pp. 316-334. Date of Electronic Publication: 2023 Jul 05. - Publication Year :
- 2023
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Abstract
- mRNA-lipid nanoparticle (mRNA-LNP) vaccines have proved their efficacy, versatility and unprecedented manufacturing speed during the COVID-19 pandemic. Here we report on the physicochemical properties, thermostability, immunogenicity, and protective efficacy of the nucleoside-modified mRNA-LNP vaccine candidate Iribovax® (also called SNEG2c). Injection of BALB/c mice, rabbits and nonhuman primates with two doses of SNEG2c induced production of high-titers of SARS-CoV-2 spike-specific and receptor-binding domain (RBD)-neutralizing antibodies in immunized animals. In addition to the strong humoral response, SNEG2c elicited substantial Th1-biased T-cell response. Sera from rhesus macaques immunized with a low dose of the vaccine showed robust spike-specific antibody titers 3-24× as high as those in convalescent sera from a panel of COVID-19 patients and 50% virus neutralization geometric mean titer of 1024 against SARS-CoV-2. Strikingly, immunization with SNEG2c completely cleared infectious SARS-CoV-2 from the upper and lower respiratory tracts of challenged macaques and protected them from viral-induced lung and trachea lesions. In contrast, the non-vaccinated macaques developed moderate to severe pulmonary pathology after the viral challenge. We present the results of repeat-dose and local tolerance toxicity and thermostability studies showing how the physicochemical properties of the mRNA-LNPs change over time and demonstrating that SNEG2 is safe, well tolerated and stable for long-term. These results support the planned human trials of SNEG2c.<br />Competing Interests: Declaration of Competing Interest The authors declare that M.R.J and S.M.J are co-inventors on pending patent applications related to the SNEG2c mRNA-LNP vaccine. The other authors declare no competing interests to this work.<br /> (Copyright © 2023 Elsevier B.V. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1873-4995
- Volume :
- 360
- Database :
- MEDLINE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Publication Type :
- Academic Journal
- Accession number :
- 37355212
- Full Text :
- https://doi.org/10.1016/j.jconrel.2023.06.025