Immune reactivity of two biological models to vaccination with inactivated vaccine QazVac against coronavirus infection COVID-19

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Abstract

Introduction. Specific prevention of a number of infectious diseases has been introduced into the vaccination schedule. The production of immunoprophylactic drugs, in order to establish standard properties, including safety and specific effectiveness, requires strict adherence to manufacturing regulations, and the reliability of the results obtained requires monitoring of these parameters. The specific effectiveness of vaccine preparations is standardized according to the indicators of stimulation of specific antibody response formed in the body of vaccinated model biological objects.

Objective. Determination of the immune reactivity of white mice to vaccination with the QazVac vaccine to establish the possibility of using them as a biological model in assessing the immunogenicity of the vaccine instead of Syrian hamsters.

Materials and methods. The immune reactivity of model animals was assessed by the seroconversion rate, dynamics of antibody titers to the SARS-CoV-2 virus formed in the body after vaccination with the test vaccine. In the case of seropositivity of animals before administration of vaccine or placebo, the level of immune reactivity was calculated by the difference in antibody titers between control and vaccinated animals or by the difference in antibody titers before and after immunization. Specific antibodies were detected and their titer was determined using a neutralization reaction.

Results. The research results showed that the tested biological models had approximately the same immune reactivity to the administration of the QazVac vaccine, confirmed by the level and dynamics of antibody titers. When analyzing the fold increase in antibody titers in comparison to those of control animals, Syrian hamsters were more reactive compared to mice. But SPF white mice were standardized in their lack of the immune reactivity to SARS-CoV-2 virus before the immunization.

Conclusion. The data obtained indicate that the immune reactivity of white mice to the administration of the QazVac vaccine in terms of the rate and dynamics of the formation of virus-neutralizing antibodies is approximately equivalent to the immune reactivity of Syrian hamsters. Before immunization with the vaccine, SPF white mice, in contrast to Syrian hamsters, do not have humoral immunity specific to the SARS-CoV-2 virus. The immune reactivity equivalent to that observed of Syrian hamsters and the absence of antibodies to the SARS-CoV-2 virus at a baseline indicate the superiority of the use of white mice in assessing the immunogenicity of vaccines against COVID-19 and/or obtaining specific factors of humoral immunity.

About the authors

Balzhan Sh. Myrzakhmetova

Research Institute for Biological Safety Problems

Author for correspondence.
Email: balzhan.msh@mail.ru
ORCID iD: 0000-0002-4141-7174

Candidate of Biological Sciences, Head of the Especially Dangerous Infectious Diseases Laboratory

Kazakhstan, Gvardeysky

Gulzhan A. Zhapparova

Research Institute for Biological Safety Problems

Email: gulzhan1003@mail.ru
ORCID iD: 0000-0001-5382-831X

Master of Biology, Senior Researcher of the Especially Dangerous Infectious Diseases Laboratory

Kazakhstan, Gvardeyskiy

Karina B. Bisenbayeva

Research Institute for Biological Safety Problems

Email: bisenbayeva.karina@bk.ru
ORCID iD: 0000-0001-5788-6074

Master of Biology, Junior Researcher of the Especially Dangerous Infectious Diseases Laboratory

Kazakhstan, Gvardeyskiy

Aizhan S. Toytanova

Research Institute for Biological Safety Problems

Email: aizhana-1308@mail.ru
ORCID iD: 0009-0004-9526-3539

Master of Biology, Junior Researcher of the Especially Dangerous Infectious Diseases Laboratory

Kazakhstan, Gvardeyskiy

Moldir S. Tuyskanova

Research Institute for Biological Safety Problems

Email: monica_94@list.ru
ORCID iD: 0000-0001-6565-082X

Master of Pedagogical Sciences (Biology), Junior Researcher of the Collection of Microorganisms Laboratory

Kazakhstan, Gvardeyskiy

Kuandyk D. Zhugunissov

Research Institute for Biological Safety Problems

Email: kuandyk_83@mail.ru
ORCID iD: 0000-0003-4238-5116

PhD, Head of the Collection of Microorganisms Laboratory

Russian Federation, Gvardeyskiy

Lespek B. Kutumbetov

Research Institute for Biological Safety Problems

Email: lespek.k@gmail.com
ORCID iD: 0000-0001-8481-0673

Doctor of Veterinary Sciences, Professor, Chief Researcher of the Especially Dangerous Infectious Diseases Laboratory

Russian Federation, Gvardeyskiy

References

  1. Young M., Crook H., Scott J., Edison P. COVID-19: Virology, variants, and vaccines. BMJ Med. 2022; 1(1): e000040. DOI: https://doi.org/10.1136/bmjmed-2021-000040
  2. Fu Y., Zhao J., Wei X., Han P., Yang L., Ren T., et al. Effectiveness and cost-effectiveness of inactivated vaccine to address COVID-19 pandemic in China: Evidence from randomized control trials and real-world studies. Front. Public Health. 2022; 10: 917732. DOI: https://doi.org/10.3389/fpubh.2022.917732
  3. Minor P.D. Live attenuated vaccines: Historical successes and current challenges. Virology. 2015; 479-480: 379–92. DOI: https://doi.org/10.1016/j.virol.2015.03.032
  4. Subbarao K. Live attenuated cold-adapted influenza vaccines. Cold Spring Harb. Perspect. Med. 2021; 11(9): a038653. DOI: https://doi.org/10.1101/cshperspect.a038653
  5. Okamura S., Ebina H. Could live attenuated vaccines better control COVID-19. Vaccine. 2021; 39(39): 5719–26. DOI: https://doi.org/10.1016/j.vaccine.2021.08.018
  6. Yarosh O.K., Wandeler A.I., Graham F.L., Campbell J.B., Prevee L. Human adenovirus type 5 vectors expressing rabies glycoprotein. Vaccine. 1996; 14(13): 1257–64. DOI: https://doi.org/10.1016/s0264-410x(96)00012-6
  7. Pushko P., Ishmukhametov А.А., Bredenbeek P.P., Lukashevich I.S. Experimental DNA-launched live-attenuated vaccines against yellow fever. Epidemiologiya i vaktsinoprofilaktika. 2019; 18(1): 18–25. DOI: https://doi.org/10.31631/2073-3046-2019-18-1-18-25 EDN: https://elibrary.ru/scwjvy (in Russian)
  8. Bugybayeva D., Kydyrbayev Z., Zinina N., Assanzhanova N., Yespembetov B., Kozhamkulov Y., et al. A new candidate vaccine for human brucellosis based on influenza viral vectors: a preliminary investigation for the development of an immunization schedule in a guinea pig model. Infect. Dis. Poverty. 2021; 10(1): 13. DOI: https://doi.org/10.1186/s40249-021-00801-y
  9. McMenamin M.E., Cowling B.J. CoronaVac efficacy data from Turkey. Lancet. 2021; 398(10314): 1873–4. DOI: https://doi.org/10.1016/S0140-6736(21)02288-1
  10. Heidary M., Kaviar V.H., Shirani M., Ghanavati R., Motahar M., Sholeh M., et al. A comprehensive review of the protein subunit vaccines against COVID-19. Front. Microbiol. 2022; 13: 927306. DOI: https://doi.org/10.3389/fmicb.2022.927306
  11. Bennett J.V., De Castro L.J., Valdespino-Gomez J.L., Garcia-Garcia Mde L., Islas-Romero R., Echaniz-Aviles G., et al. Aerosolized measles and measles-rubella vaccines induce better measles antibody booster responces than injected vaccines: randomized trials in Mexican schoolchildren. Bull. World Health Organ. 2002; 80(10): 806–12.
  12. Ecunwe E.O. Immunization by inhalation of aerosolized measles vaccine. Ann. Trop. Ped. 1990; 10(2): 145–9. DOI: https://doi.org/10.1080/02724936.1990.11747422
  13. Liashenko V.A., Krasnova V.P., Youminova N.V. Measles IgA in the nasal washings of adult volunteers and children immunized intranasally with measles vaccine L-16. Hum. Antibodies. 1999; 9(3): 143–8.
  14. Bektimirov T.A. Successes of vaccination of measles, rubella and mumps abroad. Vaktsinatsiya. 2006; (4): 4–5. (in Russian)
  15. Unasova T.N., Binyatova A.S., Phadeykina O.V., Sarkisyan K.A., Movsesyants A.A., Ignatyev G.M., et al. Analysis of the quality of national vaccine against Rubella. Voprosy virusologii. 2018; 63(2): 90–6. DOI: https://doi.org/10.18821/0507-4088-2018-63-2-90-96 EDN: https://elibrary.ru/yuujuh (in Russian)
  16. Shamsutdinova O.A. Live attenuated vaccines for the immunoprophylaxis. Infektsiya i immunitet. 2017; 7(2): 107–16. DOI: https://doi.org/10.15789/2220-7619-2017-2-107-116 EDN: https://elibrary.ru/ysktdf (in Russian)
  17. Vanaparthy R., Mohan G., Vasireddy D., Atluri P. Review of COVID-19 viral vector-based vaccines and COVID-19 variants. Infez. Med. 2021; 29(3): 328–38. DOI: https://doi.org/10.53854/liim-2903-3
  18. Logunov D.Y., Dolzhikova I.V., Zubkova O.V., Tukhvatullin A.I., Shcheblyakov D.V., Dzharullaeva A.S., et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet. 2020; 396(10255): 887–97. DOI: https://doi.org/10.1016/s0140-6736(20)31866-3
  19. Khoshnood S., Arshadi M., Akrami S., Koupaei M., Ghahramanpour H., Shariati A., et al. An overview on inactivated and live-attenuated SARS-CoV-2 vaccines. J. Clin. Lab. Anal. 2022; 36(5): e24418. DOI: https://doi.org/10.1002/jcla.24418
  20. Zakarya K., Kutumbetov L., Orynbayev M., Abduraimov Y., Sultankulova K., Kassenov M., et al. Safety and immunogenicity of a QazCovid-in® inactivated whole-virion vaccine against COVID-19 in healthy adults: A single-centre, randomised, single-blind, placebo-controlled phase 1 and an open-label phase 2 clinical trials with a 6 months follow-up in Kazakhstan. EClinicalMedicine. 2021; 39: 101078. DOI: https://doi.org/10.1016/j.eclinm.2021.101078
  21. Khairullin B., Zakarya K., Orynbayev M., Abduraimov Y., Kassenov M., Sarsenbayeva G., et al. Efficacy and safety of an inactivated whole-virion vaccine against COVID-19, QazCovid-in®, in healthy adults: A multicentre, randomised, single blind, placebo-controlled phase 3 clinical trial with a 6-month follow-up. EClinicalMedicine. 2022; 50: 101526. DOI: https://doi.org/10.1016/j.eclinm.2022.101526
  22. Nabirova D., Horth R., Smagul M., Nukenova G., Yesmagambetova A., Singer D., et al. Effectiveness of four vaccines in preventing SARS-CoV-2 infection in Almaty, Kazakhstan in 2021: retrospective population-based cohort study. Front. Public Health. 2023; 11: 1205159. DOI: https://doi.org/10.3389/fpubh.20231205159
  23. Zhugunissov K., Zakarya K., Khairullin B., Orynbayev M., Abduraimov Y., Kassenov M., et al. Development of the inactivated QazCovid-in vaccine: protective efficacy of the vaccine in Syrian hamsters. Front. Microbiol. 2021; 12: 720437. DOI: https://doi.org/10.3389/fmicb.2021.720437
  24. Nurpeisova A., Khairullin B., Abitaev R., Shorayeva K., Jekebekov K., Kalimolda E., et al. Safety and immunogenicity of the first Kazakh inactivated vaccine for COVID-19. Hum. Vaccin. Immunother. 2022; 18(5): 2087412. DOI: https://doi.org/10.1080.21645515.2022.2087412.
  25. Zhugunissov K., Kerimbayev A.A., Kopeev S., Myrzakhmetova B., Tuyskanova M., Nakhanov A., et al. SARS-CoV-2 Virus: isolation, growth, thermostability, inactivation and passages. Vestnik KazNU. Seriya biologicheskaya. 2022; 90(1): 73–89. DOI: https://doi.org/10.26577/eb.2022.v90.il.07 (in Russian)
  26. Imai M., Iwatsuki-Horimoto K., Hatta M., Loeher S., Halfmann P.J., Nakajima N., et al. Syrian hamsters as a small animal model for SARS-CoV-2 infection and countermeasure development. Proc. Natl Acad. Sci. USA. 2020: 117(28): 16587–95. DOI: https://doi.org//10.1073/pnas.2009799117
  27. Kim Y.I., Kim S.G., Kim S.M., Kim E.H., Park S.J., Yu K.M., et al. Infection and rapid transmission of SARS-CoV-2 in ferrets. Cell Host Microbe. 2020: 27(5): 704–9.e2. DOI: https://doi.org/10.1016/j.chom.2020.03.023
  28. Bao L., Deng W., Huang B., Gao H., Liu J., Ren L., et al. The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature. 2020; 583(7818): 830–3. DOI: https://doi.org/10.1038/s41586-020-2312-y
  29. Sun S.H., Chen O., Gu H.J., Yang G., Wang Y.X., Huang X.Y., et al. A mouse model of SARS-CoV-2 infection and pathogenesis. Cell Host Microbe. 2020; 28(1): 124–33.e4. DOI: https://doi.org/10.1016/j.chom.2020.05.020
  30. Soldatov V.O., Kubekina M.V., Silaeva Y.Yu., Bruter A.V., Deykin A.V. On the way from SARS-CoV-2 sensitive mice to murine COVID-19 model. Res. Results Pharmacol. 2020; 6(2): 1–7. DOI: https://doi.org/10.3897/rrpharmacology.6.53633
  31. Schlottau K., Rissmann M., Graaf A., Schön J., Sehl J., Wylezich C., et al. SARS-CoV-2 in fruit bats, ferrets, pigs, and chickens an experimental transmission study. Lancet Microbe. 2020; 1(5): e218–25. DOI: https://doi.org/10.1016/S2666-5247(20)30089-6
  32. Richard M., Kok A., de Meulder D., Bestebroer T.M., Lamers M.M., Okba N.M.A., et al. SARS-CoV-2 is transmitted via contact and via the air between ferrets. Nat. Commun. 2020; 11(1): 3496. DOI: https://doi.org/10.1038/s41467-020-17367-2
  33. Chan J.F., Zhang A.J., Yuan S., Poon V.K., Chan C.C., Lee A.C., et al. Simulation of the clinical and pathological manifestations of Coronavirus Disease 2019 (COVID-19) in golden Syrian hamster model: implications for disease pathogenesis and transmissibility. Clin. Infect. Dis. 2020; 71(9): 2428–46. DOI: https://doi.org/10.1093/cid/ciaa325
  34. Boudewijns R., Thibaut H.J., Kaptein S.J.F., Li R., Vergote V., Seldeslachts J., et al. STAT2 signaling as double-edged sword restricting viral dissemination but driving severe pneumonia in SARS-CoV-2 infected hamsters. bioRxiv. 2020. Preprint. DOI: https://doi.org/10.1101/2020.04.23.056838
  35. Sia S.F., Yan L.M., Chin A.W.H., Fung K., Choy K.T., Wong A.Y.L., et al. Pathogenesis and transmission of SARS-CoV-2 in golden hamsters. Nature. 2020; 583(7818): 834–8. DOI: https://doi.org/10.1038/s41586-020-2342-5
  36. Petrova N.V., Ganina K.K., Tarasov S.A. Susceptibility of animal species to experimental SARS-CoV-2 (Coronaviridae: Coronavirinae: Betacoronavirus; Sarbecovirus) infection. Voprosy virusologii 2021; 66(2): 103–10. DOI: https://doi.org/10.36233/0507-4088-47 EDN: https://elibrary.ru/hfvjns (in Russian)
  37. Takayama K. In vitro and Animal Models for SARS-CoV-2 research. Trends Pharmacol. Sci. 2020; 41(8): 513–7. DOI: https://doi.org/10.1016/j.tips.2020.05.005
  38. Sun J., Zhuang Z., Zheng J., Li K., Wong R.L., Liu D., et al. Generation of a broadly useful model for COVID-19 pathogenesis, vaccination and treatment. Cell. 2020; 182(3): 734–43.e5. DOI: https://doi.org/10.1016/j.cell.2020.06.010
  39. Golden J.W., Cline C.R., Zeng X., Garrison A.R., Carey B.D., Mucker E.M., et al. Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease. JCI Insight. 2020; 5(19): e142032. DOI: https://doi.org/10.1172/jci.insight.142032
  40. Martina B.E., Haagmans B.L., Kuiken T., Fouchier R.A.M., Rimmelzwaan G.F., van Amerongen G., et al. SARS virus infection of cats and ferrets. Nature. 2023; 425(6961): 915. https://doi.org/10.1038/425915a
  41. Nagornykh A.M., Tyumentsev A.I., Tyumentseva M.A., Akimkin V.G. SARS, SARS again, and MERS. Review of animal models of human respiratory syndromes caused by coronavirus infections. Zhurnal mikrobiologii, epidemiologii i immunobiologii. 2020; 97(5): 431–44. DOI: https://doi.org/10.36233/0372-9311-2020-97-5-6 EDN: https://elibrary.ru/zqdssu (in Russian)
  42. Shi J., Wen Z., Zhong G., Yang H., Wang C., Huang B., et al. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus-2. Science. 2020; 368(6494): 1016–20. DOI: https://doi.org/10.1126/science.abb7015
  43. Woolsey C., Borisevich V., Prasad A.N., Agans K.N., Deer D.J., Dobias N.S., et al. Establishment of an African green monkey model for COVID-19. bioRxiv. 2020. Preprint. DOI: https://doi.org/10.1101/2020.05.17.100289
  44. Corbett K.S., Flynn B., Foulds K.E., Francica J.R., Boyoglu-Barnum S., Werner A.P., et al. Evaluation of the mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. N. Engl. J. Med. 2020; 383(16): 1544–55. DOI: https://doi.org/10.1056/NEJMoa2024671
  45. Shan C., Yao Y.F., Yang X.L., Zhou Y.W., Gao G., Peng Y., et al. Infection with novel coronavirus (SARS-CoV-2) causes pneumonia in the rhesus macaques. Cell Res. 2020; 30(8): 670–7. DOI: https://doi.org/10.1038/s41422-020-0364-z
  46. Singh D.K., Ganatra S.R., Singh B., Cole J., Alfson K.J., Clemmons E., et al. SARS-CoV-2 infection leads to acute infection with dynamic cellular and inflammatory flux in the lung that varies across nonhuman primate species. bioRxiv. 2020. Preprint. DOI: https://doi.org/10.1101/2020.06.05.136481
  47. Williamson B.N., Feldmann F., Schwarz B., Meade-White K., Porter D.P., Schulz J., et al. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. bioRxiv. 2020. Preprint. DOI: https://doi.org/10.1101/2020.04.15.043166
  48. Yu J., Tostanoski L.H., Peter L., Mercado N.B., McMahan K., Mahrokhian S.H., et al. DNA vaccine protection against SARS-CoV-2 in rhesus macaques. Science. 2020; 369(6505): 806–11. DOI: https://doi.org/10.1126/science.abc6284
  49. Myrzakhmetova B.Sh., Zhapparova G.A., Bissenbayeva K.B., Toytanova A.S., Tuyskanova M.S., Nakhanova G.D., et al. Standartization of immunogenicity of inactivated vaccine QazVac against coronavirus infection COVID-19 from an epidemiologically relevant strain. Eurasian Journal of Applied Biotechnology. 2023; (4): 31–41. DOI: https://doi.org/10.11134/btp.4.2023.4 (in Russian)
  50. Reed L.J., Muench Simple H.A. Method of estimating fifty per cent endpoints. Am. J. Epidemiol. 1938; 27(3): 493–7. DOI: https://doi.org/10.1093/oxfordjournals.aje.a118408(1938)
  51. Myrzagaliev A.K., Shcherbakova I.V. Possibilities of using the Student’s t-test for analyzing medical research data. Byulleten’ meditsinskikh internet-konferentsii. 2014; 4(11): 1275. EDN: https://elibrary.ru/tgglen (in Russian)
  52. Guo B., Yuan Y. A comparative review of methods for comparing means using partially paired data. Stat. Methods Med. Res. 2017; 26(3): 1323–40. DOI: https://doi.org/10.1177/0962280215577111
  53. Tuyskanova M.S., Zhugunissov K.D., Ozaslan M., Myrzakhmetova B.Sh., Kutumbetov L.B. Clinical symptoms and signs in hamsters during experimental infection with the SARS-CoV-2 virus (Coronaviridae: Betacoronavirus). Voprosy virusologii. 2023; 68(6): 513–25. DOI: https://doi.org/10.36233/0507-4088-202 EDN: https://elibrary.ru/kivlek (in Russian)
  54. Moore D., McCabe G. Introduction to the Practice of Statistics. New York: Freeman W.H. and Co; 1989.
  55. Zar J.H. Biostatistical Analysis. Upper Saddle River, N.J.: Prentice Hall; 1999: 43–5.
  56. Student. The probable error of a mean. Biometrika. 1908; 6(1): 1–25.
  57. Khairullin B., Zakarya K., Orynbayev M., Kassenov M., Sultankulova K., Zhugunissov K., et al. Method for obtaining an inactivated vaccine for the prevention of COVID-19. Patent RK № 34761; 2020. (in Russian)
  58. State Pharmacopoeia of the Republic of Kazakhstan. First edition, issue 1; 2008. (in Russian)
  59. Mironov A.N. Guidelines for Conducting Preclinical Studies of Medicinal Products [Rukovodstvo po provedeniyu doklinicheskikh issledovanii lekarstvennykh sredstv.]. Moscow; 2021. (in Russian)

Copyright (c) 2024 Myrzakhmetova B.S., Zhapparova G.A., Bisenbayeva K.B., Toytanova A.S., Tuyskanova M.S., Zhugunissov K.D., Kutumbetov L.B.

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