Animal Pre-Clinical Study of an Inactivated SARS-CoV-2 Vaccine candidate (Osvid-19 ®): Immunogenicity, Protective, and Safety Aspects

Zohre Eftekhari; Seyed Dawood Mousavi Nasab; Ruhollah Dorostkar; Ali Akbar Pourfathollah; Mahyar Jeloudai Mamaghani; Seyed Mehdi Hassanzadeh; Hooman Kaghazian

doi:10.47750/jptcp.2023.30.09.013

Zohre Eftekhari

Biotechnology Departement, Pasteur Institute of Iran, Tehran, Iran

Seyed Dawood Mousavi Nasab

Department of Research and Development, Research& Production Complex, Pasteur Institute of Iran, Tehran

Ruhollah Dorostkar

Kian Gen Azma Company, Tehran, Iran

Ali Akbar Pourfathollah

Immunology Department, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

Mahyar Jeloudai Mamaghani

Department of Quality, Paya Fan Yakhteh Alborz Co, Alborz, Iran

Seyed Mehdi Hassanzadeh

Department of BCG Vaccine Prodution, Research& Production Complex, Pasteur Institute of Iran, Tehran, Iran

Hooman Kaghazian

Biotechnology Departement, Pasteur Institute of Iran, Tehran, Iran

Keywords

immunogenicity, toxicology, vaccine

Abstract

Background: This study aimed to evaluate the outcomes of preclinical studies on the safety and immunogenicity of an inactivated COVID-19 vaccine candidate to warrant further clinical evaluation.
Methods: SARS-CoV-2 positive nasopharyngeal swab specimens were confirmed by real-time polymerase chain reaction and next-generation sequencing. The safety and immunogenicity tests of the COVID-19 vaccine were carried out in rats and Rhesus monkeys, and Balb/C mice and Rhesus monkeys, respectively.
Results: The candidate vaccine was well tolerated and induced promising levels of SARS-CoV-2–specific IgG1, IgG2a, and Granzyme B in Balb/C mice, and anti-SARS-CoV-2 spike IgG and neutralizing antibodies in Rhesus monkeys. Based on cVNT results, the inactivated vaccine in 0.5 and 1 μg/100 μL doses was able to induce a neutralizing effect against the SARS-CoV-2 virus up to a dilution of 1:512 and 1:1000. The protective efficacy of the vaccine candidate was challenged with 2 ×108 PFU of live viruses and confirmed by lung CT scan and histopathological evaluations compared to the control group. Repeated intramuscular injection of the candidate vaccine was generally well-tolerated in Rats and Rhesuses. No significant side effects were observed in rats injected with ten full human doses and in the Rhesus monkeys with three full human doses.
Conclusion: Based on the findings presented in this study, it is recommended that this vaccine be moved into human testing commencing with a phase I clinical trial.

Abstract 141 | PDF Downloads 162

References

1. ur Rehman MF, Fariha C, Anwar A, Shahzad N, Ahmad M, Mukhtar S, et al. Novel coronavirus disease (COVID-19) pandemic: A recent mini review. Comput Struct Biotechnol J. 2020;
2. Nannoni S, de Groot R, Bell S, Markus HS. Stroke in COVID-19: a systematic review and meta-analysis. Int J Stroke. 2021;16(2):137–49.
3. V’kovski P, Kratzel A, Steiner S, Stalder H, Thiel V. Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol. 2021;19(3):155–70.
4. Mittal A, Manjunath K, Ranjan RK, Kaushik S, Kumar S, Verma V. COVID-19 pandemic: Insights into structure, function, and hACE2 receptor recognition by SARS-CoV-2. PLoS Pathog. 2020;16(8):e1008762.
5. Hu B, Guo H, Zhou P, Shi Z-L. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2021;19(3):141–54.
6. Dai L, Gao GF. Viral targets for vaccines against COVID-19. Nat Rev Immunol. 2021;21(2):73–82.
7. Hong J, Jhun H, Choi Y-O, Taitt AS, Bae S, Lee Y, et al. Structure of SARS-CoV-2 Spike glycoprotein for therapeutic and preventive target. Immune Netw. 2021;21(1).
8. Haque A, Pant AB. Efforts at COVID-19 vaccine development: challenges and successes. Vaccines. 2020;8(4):739.
9. Organization WH. Guidelines on clinical evaluation of vaccines: regulatory expectations. WHO Tech Rep Ser. 2004;924.
10. Chakraborty S, Mallajosyula V, Tato CM, Tan GS, Wang TT. SARS-CoV-2 vaccines in advanced clinical trials: Where do we stand. Adv Drug Deliv Rev. 2021;
11. Flanagan KL, Best E, Crawford NW, Giles M, Koirala A, Macartney K, et al. Progress and pitfalls in the quest for effective SARS-CoV-2 (COVID-19) vaccines. Front Immunol. 2020;11:2410.
12. Lounis M, Rais MA, Bencherit D, Aouissi HA, Oudjedi A, Klugarová J, et al. Side Effects of COVID-19 Inactivated Virus vs. Adenoviral Vector Vaccines: Experience of Algerian Healthcare Workers. Front Public Heal. 2022;10.
13. Zhang M-X, Zhang T-T, Shi G-F, Cheng F-M, Zheng Y-M, Tung T-H, et al. Safety of an inactivated SARS-CoV-2 vaccine among healthcare workers in China. Expert Rev Vaccines. 2021 Jul;20(7):891–8.
14. Wang J, Deng C, Liu M, Liu Y, Li L, Huang Z, et al. Four doses of the inactivated SARS-CoV-2 vaccine redistribute humoral immune responses away from the receptor binding domain. medRxiv. 2022;
15. Stauffer F, El-Bacha T, Da Poian AT. Advances in the development of inactivated virus vaccines. Recent Pat Antiinfect Drug Discov. 2006;1(3):291–6.
16. Del Giudice G, Rappuoli R. Inactivated and adjuvanted influenza vaccines. Influ Pathog Control II. 2014;151–80.
17. Levine MM, Sztein MB. Vaccine development strategies for improving immunization: the role of modern immunology. Nat Immunol. 2004;5(5):460–4.
18. Zepp F. Principles of vaccine design—lessons from nature. Vaccine. 2010;28:C14–24.
19. Dai X, Xiong Y, Li N, Jian C. Vaccine types. In: Vaccines-the History and Future. IntechOpen; 2019.
20. Mellet J, Pepper MS. A COVID-19 vaccine: big strides come with big challenges. Vaccines. 2021;9(1):39.
21. Pato TP, Souza MCO, Mattos DA, Caride E, Ferreira DF, Gaspar LP, et al. Purification of yellow fever virus produced in Vero cells for inactivated vaccine manufacture. Vaccine. 2019;37(24):3214–20.
22. Sanders B, Koldijk M, Schuitemaker H. Inactivated viral vaccines. In: Vaccine analysis: strategies, principles, and control. Springer; 2015. p. 45–80.
23. Pasquale A Di, Preiss S, Silva FT Da, Garçon N. Vaccine adjuvants: from 1920 to 2015 and beyond. Vaccines. 2015;3(2):320–43.
24. Uittenbogaard JP, Zomer B, Hoogerhout P, Metz B. Reactions of β-propiolactone with nucleobase analogues, nucleosides, and peptides: Implications for the inactivation of viruses. J Biol Chem. 2011;286(42):36198–214.
25. Rabaan AA, Al-Ahmed SH, Sah R, Tiwari R, Yatoo M, Patel SK, et al. SARS-CoV-2/COVID-19 and advances in developing potential therapeutics and vaccines to counter this emerging pandemic. Ann Clin Microbiol Antimicrob. 2020;19(1):1–37.
26. Dubé E, Laberge C, Guay M, Bramadat P, Roy R, Bettinger JA. Vaccine hesitancy: an overview. Hum Vaccin Immunother. 2013;9(8):1763–73.
27. Pandey SC, Pande V, Sati D, Upreti S, Samant M. Vaccination strategies to combat novel corona virus SARS-CoV-2. Life Sci. 2020;256:117956.28. Malik JA, Mulla AH, Farooqi T, Pottoo FH, Anwar S, Rengasamy KRR. Targets and strategies for vaccine development against SARS-CoV-2. Biomed Pharmacother. 2021;111254.
29. Aubrit F, Perugi F, Léon A, Guéhenneux F, Champion-Arnaud P, Lahmar M, et al. Cell substrates for the production of viral vaccines. Vaccine. 2015 Nov;33(44):5905–12.
30. Takayama K. In vitro and animal models for SARS-CoV-2 research. Trends Pharmacol Sci. 2020;41(8):513–7.
31. Jureka AS, Silvas JA, Basler CF. Propagation, inactivation, and safety testing of SARS-CoV-2. Viruses. 2020;12(6):622.
32. Kalnin K V, Plitnik T, Kishko M, Zhang J, Zhang D, Beauvais A, et al. Immunogenicity and efficacy of mRNA COVID-19 vaccine MRT5500 in preclinical animal models. npj Vaccines. 2021;6(1):1–12.
33. Gao Q, Bao L, Mao H, Wang L, Xu K, Yang M, et al. Development of an inactivated vaccine candidate for SARS-CoV-2. Science (80- ). 2020;369(6499):77–81.
34. Yao Y-F, Wang Z-J, Jiang R-D, Hu X, Zhang H-J, Zhou Y-W, et al. Protective Efficacy of Inactivated Vaccine against SARS-CoV-2 Infection in Mice and Non-Human Primates. Virol Sin. 2021;1–11.
35. Prompetchara E, Ketloy C, Palaga T. Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pacific J allergy Immunol. 2020;38(1):1–9.
36. Graham BS. Rapid COVID-19 vaccine development. Science (80- ). 2020;368(6494):945–6.
37. Kar T, Narsaria U, Basak S, Deb D, Castiglione F, Mueller DM, et al. A candidate multi-epitope vaccine against SARS-CoV-2. Sci Rep. 2020;10(1):1–24.
38. Zhang B, Hu Y, Chen L, Yau T, Tong Y, Hu J, et al. Mining of epitopes on spike protein of SARS-CoV-2 from COVID-19 patients. Cell Res. 2020;30(8):702–4.
39. Yang D, Leibowitz JL. The structure and functions of coronavirus genomic 3′ and 5′ ends. Virus Res. 2015;206:120–33.
40. Kandeil A, Mostafa A, Hegazy RR, El-Shesheny R, El Taweel A, Gomaa MR, et al. Immunogenicity and Safety of an Inactivated SARS-CoV-2 Vaccine: Preclinical Studies. Vaccines. 2021;9(3):214.
41. Walsh EE, Frenck Jr RW, Falsey AR, Kitchin N, Absalon J, Gurtman A, et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N Engl J Med. 2020;383(25):2439–50.
42. Frenck Jr RW, Klein NP, Kitchin N, Gurtman A, Absalon J, Lockhart S, et al. Safety, immunogenicity, and efficacy of the BNT162b2 Covid-19 vaccine in adolescents. N Engl J Med. 2021;

PDF

Published

May 5, 2023

DOI https://doi.org/10.47750/jptcp.2023.30.09.013

How to Cite

Zohre Eftekhari, Seyed Dawood Mousavi Nasab, Ruhollah Dorostkar, Ali Akbar Pourfathollah, Mahyar Jeloudai Mamaghani, Seyed Mehdi Hassanzadeh, & Hooman Kaghazian. (2023). Animal Pre-Clinical Study of an Inactivated SARS-CoV-2 Vaccine candidate (Osvid-19 ®): Immunogenicity, Protective, and Safety Aspects. Journal of Population Therapeutics and Clinical Pharmacology, 30(9), 111–130. https://doi.org/10.47750/jptcp.2023.30.09.013