Immune Responses Following Administration of Whole Gamma Irradiated SARS-CoV-2 Vaccine Stabilized With Disaccharide Trehalose on Syrian Hamster Model

Abstract

Background The SARS-CoV-2 virus is the causative agent of the emerging respiratory zoonosis disease. One of the most important requirements for the control of emerging diseases is the development of vaccines within a short period of time. Methods The use of ionizing radiation to inactivate pathogens has been developed for the rapid production of effective vaccines. In this study, the SARS-CoV-2 virus was isolated from tracheal swabs of an infected man, confirmed by RT-PCR, and propagated on Vero cells. The SARS-CoV-2 virus was irradiated with 14 kGy gamma radiation to completely inactivate it. Evaluation of the antigenic properties of the spike protein subunit S1 showed that the gamma-irradiated virus samples had intact antigens. The gamma-irradiated SARS-CoV-2 virus and formalin-treated virus were used to immunize Syrian hamsters in four vaccine formulations. Results The titer of neutralizing antibodies increased significantly in all vaccinated groups 3 weeks after the second and third vaccinations. Secretory IgA was examined in nasal lavage and NALT fluids and showed that the concentration of sIgA in irradiated vaccine plus trehalose increased significantly 3 weeks after the second and third vaccinations. The splenic lymphocyte proliferation assay showed a significant increase in all vaccinated hamsters, but the increase was greater in irradiated vaccine plus trehalose and irradiated vaccine plus alum. Conclusion In addition, we can introduce irradiated inactivated vaccine SARS-CoV-2 plus disaccharide trehalose via intranasal route of administration and another irradiated inactivated vaccine SARS-CoV-2 plus alum via subcutaneous route as safe and efficient vaccines against COVID-19 which can stimulate mucosal, humeral and cellular immunity.