Abstract
Several vaccine candidates for COVID-19 have been developed, and few vaccines received emergency approval with an acceptable level of efficacy and safety. We herein report the development of the first recombinant protein-based vaccine in Iran based on the recombinant SARS-CoV-2 spike protein in its monomeric (encompassing amino acid 1-674 for S1 and 685-1211 for S2 subunits) and trimer form (S-Trimer) formulated in the oil-in-water adjuvant system RAS-01 (Razi Adjuvant System-01). The safety and immunity of the candidate vaccine, referred to as RAZI-COV PARS, were evaluated in Syrian hamster, BALB/c mice, Pirbright guinea pig, and New Zeeland white (NZW) rabbit. All vaccinated animals received two intramuscular (IM) and one intranasal (IN) candidate vaccine at 3-week intervals (days 0, 21, and 51). The challenge study was performed intranasally with 5×10 6 pfu of SARS-CoV-2 35 days post-vaccination. None of the vaccinated mice, hamsters, guinea pigs, or rabbits showed any changes in general clinical observations; body weight and food intake, clinical indicators, hematology examination, blood chemistry, and pathological examination of vital organs. Safety of vaccine after the administration of single and repeated dose was also established. Three different doses of candidate vaccine stimulated remarkable titers of neutralizing antibodies, S1, Receptor-Binding Domain (RBD), and N-terminal domain (NTD) specific IgG antibodies as well as IgA antibodies compared to placebo and control groups (P<0.01). Middle and high doses of RAZI-COV PARS vaccine significantly induced a robust and quick immune response from the third-week post-immunization. Histopathological studies on vaccinated hamsters showed that the challenge with SARS-CoV-2 did not induce any modifications in the lungs. The protection of the hamster was documented by the absence of lung pathology, the decreased virus load in the lung, rapid clearance of the virus from the lung, and strong humoral and cellular immune response. These findings confirm the immunogenicity and efficacy of the RAZI-COV PARS vaccine. Of the three tested vaccine regimens, the middle dose of the vaccine showed the best protective immune parameters. This vaccine with heterologous prime-boost vaccination method can be a good candidate to control the viral infection and its spread by stimulating central and mucosal immunity.
Keywords: COVID-19; RAZI-COV PARS; SARS-CoV-2 preclinical study; spike protein; vaccine.
【저자키워드】 COVID-19, Vaccine, Spike protein, RAZI-COV PARS, SARS-CoV-2 preclinical study, 【초록키워드】 SARS-CoV-2, viral infection, Efficacy, Vaccine, High dose, immune response, vaccination, Safety, Immunity, Neutralizing antibodies, hamsters, Cellular immune response, lung, virus, immune, Spread, Iran, mice, RBD, Lungs, SARS-CoV-2 spike protein, vaccine candidate, Efficacy and safety, Placebo, adjuvant, NTD, hamster, blood chemistry, virus load, parameters, intranasal, Protective, intramuscular, N-terminal domain, Lung pathology, Amino acid, mucosal, administration, dose, humoral, heterologous prime-boost, control group, regimens, approval, candidate vaccine, trimer, organs, BALB/c mice, Modification, subunits, clearance, middle, repeated, robust, Pathological examination, stimulated, tested, significantly, intranasally, evaluated, was performed, changes in, absence, induce, the vaccine, interval, New, IgA antibody, different dose, monomeric, pfu, specific IgG antibody, 【제목키워드】 Safety, animal, Model, candidate, Combined, Against, Preclinical,