Veterinary Research Forum
Vet Res Forum

Role of gamma irradiation and disaccharide trehalose to induce immune responses in Syrian hamster model against Iranian SARS-CoV-2 virus isolate

Document Type : Original Article

Authors

Farahnaz Motamedi Sedeh 1
Akbar Khorasani 2
Mohsen Lotfi 3
Seyed Morteza Mousavi 1, 4
Arash Arbabi 5
Seyedeh Maede Hosseini 5

1 Department of Veterinary and Animal Diseases, Nuclear Agriculture Research School, Nuclear Science and Technology Research Institute, Karaj, Iran

2 Department of FMD Vaccine, Razi Vaccine and Serum Research, Education and Extension Organization (AREEO), Karaj, Iran

3 Department of Quality Control, Razi Vaccine and Serum Research, Education and Extension Organization (AREEO), Karaj, Iran

4 Iran Veterinary Organization, Mashhad, Iran

5 MD Student, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

https://doi.org/10.30466/vrf.2024.2022838.4172
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is the causative agent of the emerging zoonotic respiratory disease. One of the most important prerequisites for combating emerging diseases is the development of vaccines within a short period of time. In this study, antigen-irradiated, inactivated SARS-CoV-2 viruses and the disaccharide trehalose were used to enhance immune responses in the Syrian hamster. The SARS-CoV-2 virus was isolated from tracheal swabs, confirmed by Real-Time Polymerase Chain Reaction (RT-PCR), and propagated on Vero cells. For inactivation, it was irradiated with 14.00 kGy gamma radiation. Evaluation of the antigenic properties of the spike protein subunit S1 showed that the antigens were intact after gamma irradiation. The gamma-irradiated and formalin-treated viruses were used to immunize hamsters in four vaccine formulations. Neutralizing antibodies increased significantly in all vaccinated groups three weeks after the second and third vaccinations. The concentration of secretory immunoglobulin A in the irradiated vaccine plus trehalose increased significantly in nasal lavage and nasopharyngeal-associated lymphoid tissue fluids three weeks after the second and third vaccinations. The lymphocyte proliferation test in the spleen showed a significant increase in all vaccinated hamsters, but the increase was greater in irradiated vaccine plus trehalose and irradiated vaccine plus alum. We can recommend the irradiated inactivated vaccine SARS-CoV-2 plus trehalose (intra-nasal) and another irradiated inactivated vaccine SARS-CoV-2 plus alum (subcutaneous) as safe vaccines against coronavirus disease of 2019 (COVID-19), which can stimulate mucosal, humeral, and cellular immunities. However, the protectivity of the vaccine against COVID-19 in vaccinated hamsters must be investigated in a challenge test to assess the potency and efficiency of vaccine.

Keywords

Gamma irradiation
Immune response
Inactivated vaccine
Mucosal immunity
SARS-CoV-2 virus

Subjects

  1. Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 2019; 17(3): 181-192.
  2. Santos IA, Grosche VR, Bergamini FRG, et al. Antivirals against coronaviruses: candidate drugs for SARS-CoV-2 treatment? Front Microbiol 2020; 11: 1818. doi: 10.3389/fmicb.2020.01818.
  3. Rogers TF, Zhao F, Huang D, et al. Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Science 2020; 369(6506): 956-963.
  4. Finkensieper J, Issmail L, Fertey J, et al. Low-energy electron irradiation of tick-borne encephalitis virus provides a protective inactivated vaccine. Front Immunol 2022; 13: 825702. doi: 10.3389/fimmu. 2022.825702.
  5. Mollaei Alamuti M, Ravanshad M, Motamedi-Sedeh F, et al. Immune response of gamma-irradiated inactivated bivalent polio vaccine prepared plus trehalose as a protein stabilizer in a mouse model. Intervirology 2021; 64(3): 140-146.
  6. Unger H, Kangethe RT, Liaqat F, et al. Advances in irradiated livestock vaccine research and production addressing the unmet needs for farmers and veterinary services in FAO/IAEA member states. Front Immunol 2022; 13: 853874. doi: 10.3389/fimmu.2022.853874.
  7. Mullbacher A, Pardo J, Furuya Y. SARS-CoV-2 vaccines: inactivation by gamma irradiation for T and B cell Pathogens 2020; 9(11): 928. doi: 10.3390/ pathogens9110928.
  8. Bhatia SS, Pillai SD. Ionizing radiation technologies for vaccine development - a mini review. Front Immunol 2022: 13: 845514. doi: 10.3389/fimmu.2022.845514.
  9. Jiang RD, Liu MQ, Chen Y, et al. Pathogenesis of SARS-CoV-2 in transgenic mice expressing human angiotensin-converting enzyme. Cell 2020; 182(1): 50-58. e8. doi: 10.1016/j.cell.2020.05.027.
  10. Turan RD, Tastan C, Dilek Kancagi D, et al. Gamma-irradiated SARS-CoV-2 vaccine candidate, OZG-38.61.3, confers protection from SARS-CoV-2 challenge in human ACEII-transgenic mice. Sci Rep 2021; 11(1): 15799. doi: 10.1038/s41598-021-95086-4.
  11. Horiuchi S, Oishi K, Carrau L, et al. Immune memory from SARS-CoV-2 infection in hamsters provides variant-independent protection but still allows virus transmission. Sci Immunol 2021; 6(66): eabm3131. doi: 10.1126/sciimmunol.abm3131.
  12. Haghighi A, Khorasani A, Karimi P, et al. Different formulations of inactivated SARS-CoV-2 vaccine candidates in human compatible adjuvants: potency studies in mice showed different platforms of immune responses. Viral Immunol 2022; 35(10): 663-672.
  13. Motamedi Sedeh F, Khalili I, Wijewardana V, et al. Improved whole gamma irradiated avian influenza subtype H9N2 virus vaccine using trehalose and optimization of vaccination regime on broiler chicken. Front Vet Sci 2022, 9: 907369. doi: 10.3389/fvets. 2022.907369.
  14. Motamedi-Sedeh F, Soleimanjahi H, Jalilian AR, et al. Development of protective immunity against inactivated Iranian isolate of foot-and-mouth disease virus type O/IRN/2007 using gamma ray-irradiated vaccine on BALB/c mice and Guinea pigs. Intervirology 2015; 58(3): 190-196.
  15. Lee HJ, Yoon YS, Lee SJ. Mechanism of neuroprotection by trehalose controversy surrounding autophagy induction. Cell Death Dis 2018, 9(7): 712. doi: 10.1038/s41419-018-0749-9.
  16. Martinon D, Borges VF, Gomez AC, et al. Potential fast COVID-19 containment with trehalose. Front Immunol 2020; 11: 1623. doi: 10.3389/fimmu.2020.01623.
  17. Motamedi-Sedeh F, Saboorizadeh A, Khalili I, et al. Carboxymethyl chitosan bounded iron oxide nanoparticles and gamma‐irradiated avian influenza subtype H9N2 vaccine to development of immunity on mouse and chicken. Vet Med Sci 2022; 8(2): 626-634.
  18. Richards AB, Krakowka S, Dexter LB, et al. Trehalose: a review of properties, history of use and human tolerance, and results of multiple safety studies. Food Chem Toxicol 2002; 40(7): 871-898.
  19. Javan S, Motamedi-Sedeh F, Dezfulian M. Reduction of viral load of avian influenza A virus (H9N2) on SPF eggs and cell line by gamma irradiation. Bulg J Vet Med 2021: 24(1): 144-151.
  20. Alsharifi M, Müllbacher A. The gamma-irradiated influenza vaccine and the prospect of producing safe vaccines in general. Immunol Cell Biol 2021: 88(2): 103-104.
  21. Sabbaghi A, Zargar M, Zolfaghari MR, et al. Protective cellular and mucosal immune responses following nasal administration of a whole gamma-irradiated influenza A (subtype H1N1) vaccine adjuvanted with interleukin-28B in a mouse model. Arch Virol 2021: 166(2): 545-557.
  22. Premkumar L, Segovia-Chumbez B, Jadi R, et al. The receptor-binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients. Sci Immunol 2020: 5(48): eabc8413. doi: 10.1126/sciimmunol.abc8413.
  23. Brandtzaeg P. Immunobiology of the tonsils and adenoids. In: Mestecky J, Strober W, Russell MW, et al. (Eds). Mucosal immunology. 4th Oslo, Norway: Academic Press 2015: 1985-2016.
  24. Russell MW, Moldoveanu Z, Ogra PL, et al. Mucosal immunity in COVID-19: a neglected but critical aspect of SARS-CoV-2 infection. Front Immunol 2020: 11: 611337. doi: 10.3389/fimmu.2020.611337.
  25. Twigg HL 3rd. Humoral immune defense (antibodies): recent advances. Proc Am Thorac Soc 2005; 2 (5): 417-421.
  26. Wang L, Nicols A, Turtle L, et al. T cell immune memory after COVID-19 and vaccination. BMJ MED 2023; 2(1): e000468. doi:10.1136/bmjmed-2022-000468.
  27. Seo HS. Application of radiation technology in vaccines development. Clin Exp Vaccine Res 2015: 4(2): 145-158.
  28. Dorey S, Gaston F, Dupuy N, et al. Reconciliation of pH, conductivity, total organic carbon with carboxylic acids detected by ion chromatography in solution after contact with multilayer films after γ-irradiation. Eur J Pharm Sci 2018: 117: 216-226.
  29. Ohshima H, Iida Y, Matsuda A, et al. Damage induced by hydroxyl radicals generated in the hydration layer of gamma-irradiated frozen aqueous solution of DNA. J Radiat Res 1996: 37(3): 199-207.
  30. Lomax ME, Folkes LK, O’Neill P. Biological consequences of radiation-induced DNA damage: relevance to radiotherapy. Clin Oncol (R Coll Radiol) 2013: 25(10): 578-585.
  31. Prompetchara E, Ketloy C, Alameh MG, et al. Immunogenicity and protective efficacy of SARS-CoV-2 mRNA vaccine encoding secreted non-stabilized spike in female mice. Nat Commun 2023: 14(1): 2309. doi: 10.1038/s41467-023-37795-0.
  32. Offersgaard A, Duarte Hernandez CR, Feng S, et al. An inactivated SARS-CoV-2 vaccine induced cross-neutralizing persisting antibodies and protected against challenge in small animals. iScience 2023: 26(2): 105949. doi: 10.1016/j.isci.2023.105949.
  33. Barda N, Dagan N, Cohen C, et al. Effectiveness of a third dose of the BNT162b2 mRNA COVID-19 vaccine for preventing severe outcomes in Israel: an observational study. Lancet 2021: 398(10316): 2093-2100.
  34. Feng S, Phillips DJ, White T, et al. Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection. Nat Med 2021: 27(11): 2032-2040.
  35. Nasiri H, Valedkarimi Z, Aghebati-Maleki L, et al. Production and purification of polyclonal antibody against F(ab')2 fragment of human immunoglobulin G. Vet Res Forum 2017; 8(4): 307-312.
  36. Twigg HL 3rd. Humoral immune defense (antibodies): recent advances. Proc Am Thorac Soc 2005: 2(5):
    417-421.
  37. Jia Z, Wang K, Xie M, et al. A third dose of inactivated vaccine augments the potency, breadth, and duration of anamnestic responses against SARS-CoV-2. Protein Cell 2024; pwae033. doi: 10.1093/procel/pwae033.
  38. Pilapitiya D, Wheatley AK, Tan HX. Mucosal vaccines for SARS-CoV-2: triumph of hope over experience. EBioMed 2023: 92: 104584.
  39. Grifoni A, Weiskopf D, Ramirez SI, et al. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell 2020; 181(7): 1489-1501.
  40. Lowy RJ, Vavrina GA, LaBarre DD. Comparison of gamma and neutron radiation inactivation of influenza A virus. Antiviral Res 2001; 52(3): 261-273.
  41. Mullbacher A, Marshall ID, Blanden RV. Cross-reactive cytotoxic T cells to alphavirus infection. Scand J Immunol 1979; 10(4): 291-296.
  42. Müllbacher A, Marshall ID, Ferris P. Classification of Barmah Forest virus as an alphavirus using cytotoxic T cell assays. J Gen Virol 1986; 67(Pt 2): 295-299.
Veterinary Research Forum
Volume 15, Issue 12
December 2024
Pages 681-689

  • Receive Date 21 February 2024
  • Revise Date 13 April 2024
  • Accept Date 07 May 2024

Home

Guide for Authors

Submit Manuscript

Reviewers

Contact Us