Characterization of Stability, Safety and Immunogenicity of the Mrna Lipid Nanoparticle Vaccine Iribovax® Against Covid-19 in Nonhuman Primates Publisher Pubmed



Zamani P^{1, 2} ; Mashreghi M^{1, 2} ; Rezazade Bazaz M^{1, 3} ; Zargari S⁴ ; Alizadeh F⁴ ; Dorrigiv M² ; Abdoli A^{5, 6} ; Aminianfar H^{7, 8} ; Hatamipour M¹ ; Zarqi J¹ ; Behboodifar S¹ ; Samsami Y⁴ ; Khorshid Sokhangouy S⁴ ; Sefidbakht Y⁹ Show All Authors
Source: Journal of Controlled Release Published:2023

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. © 2023 Elsevier B.V.