Preview

Epidemiology and Vaccinal Prevention

Advanced search

Methods for Virus Inactivation in the Production Technology of Whole Virion Vaccines

https://doi.org/10.31631/2073-3046-2025-24-6-77-91

Abstract

Relevance. The study of virus inactivation mechanisms remains a priority in the development of inactivated whole-virion vaccines. Criteria for selecting a suitable inactivator include complete elimination of viral infectivity and preservation of a high level of immunogenicity in the final product.

Aim. This work examines the action mechanisms of both classical inactivators (formalin, betapropiolactone) and UV irradiation. Besides, the article describes the latest promising inactivation approaches by hydrogen peroxide, gamma irradiation and psoralen.

Conclusion. The inactivator optimal choice depends on many factors: the nature of the virus, the required level of safety, manufacturing technology, and the final vaccine properties. The formalin and beta-propiolactone continue to dominate in the licensed vaccines production. Experimental vaccine preparations inactivated with hydrogen peroxide or by physical methods have shown a high level of immunogenic activity in various laboratory animal models. Despite the positive results, a new inactivating agent introduction requires significant effort and long-term testing to confirm its effectiveness and safety.

About the Authors

M. S. Egorova
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian academy of Sciences
Russian Federation

Egorova Maria S., Cand. Sci. (Biol.), Senior Researcher of the Laboratory of Hemorrhagic Fevers

building 1, household 8, settlement Moskovsky, settlement of the Institute of Poliomyelitis, Moscow, 108819

+7 (977) 354-16-19



S. S. Kurashova
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian academy of Sciences
Russian Federation

Svetlana S. Kurashova – Cand. Sci. (Med.), Leading Researcher of the Laboratory of Hemorrhagic Fevers

Moscow

+7 (965) 309-32-41



A. N. Vetrova
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian academy of Sciences
Russian Federation

Anna N. Vetrova  – junior research of the Laboratory Hemorrhagic Fevers 

Moscow



T. K. Dzagurova
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian academy of Sciences
Russian Federation

Tamara K. Dzagurova – Dr. Sci. (Med.), Head of the Laboratory of Hemorrhagic Fevers 

Moscow

+7 (926) 446-09-60



References

1. Salmon DE, Smith T. On a new method of producing immunity from contagious diseases. Am Vet Rev. 1886; 10: 63–69.

2. Wright AE., Semple D. Remarks on vaccination against typhoid fever. British medical journal.1897; 1:256.

3. Haffkine WM. Protective inoculation against plague and cholera. BMJ. 1899; 1: 35–36.

4. Weller TH, Robbins FC, Enders JF. Cultivation of poliomyelitis virus in cultures of human foreskin and embryonic tissues.Proceedings of the Society for Experimental Biology and Medicine. 1949; 72 (1):153–155. doi: 10.3181/00379727-72-17359

5. Enders JF, Weller TH., Robbins FC. Cultivation of the Lansing strain of poliomyelitis virus in cultures of various human embryonic tissues. Science. 1949; 109(2822):85-87. doi:10.1126/science.109.2822.85

6. Salk JE, Bennett BL, Lewis LJ, et al. Studies in human subjects on active immunization against poliomyelitis: 1. A preliminary report of experiments in progress .Journal of the American Medical Association. 1953; 151(13):1081–1098.

7. Wodi AP, Morelli V. Principles of Vaccination. In: Epidemiology and Prevention of Vaccine-Preventable Diseases. 14th edition. Washington: DC: Public Health Foundation, Centers for Disease Control and Prevention; 2021. P. 225–238.

8. Hess RD, Weber F, Watson K. Regulatory, biosafety and safety challenges for novel cells as substrates for human vaccines. Vaccine. 2012; 30(17): 2715–2727. doi: 10.1016/j.vaccine.2012.02.015

9. Barrett PN, Mundt W, Kistner O, et al. Vero cell platform in vaccine production: moving towards cell culture-based viral vaccines. Expert review of vaccines. 2009; 8(5): 607–618. doi: 10.1586/erv.09.19

10. Delrue I, Verzele D, Madder A, et al. Inactivated virus vaccines from chemistry to prophylaxis: merits, risks and challenges Expert review of vaccines. 2012; 11(6): 695–719. doi: 10.1586/erv.12.38

11. Budowsky EI, Bresler SE, Friedman EA, et al. Principles of selective inactivation of viral genome: I. UV-induced inactivation of influenza virus. Archives of virology.1981; 68(3- 4): 239–247. doi: 10.1007/BF01314577

12. Nims RW, Plavsic M. Polyomavirus inactivation–a review. Biologicals. 2013; 41(2): 63–70. doi: 10.1016/j.biologicals.2012.09.011

13. Madhusudana SN, Shamsundar R, Seetharaman S. In vitro inactivation of the rabies virus by ascorbic acid. International journal of infectious diseases. 2004; 8(1):21–25. doi:10.1016/j.ijid.2003.09.002

14. Mihalishin DV, Mikhalishin VV., Gochmuradov YM., et al. Inaktivaciya virusa yashchura dlya izgotovleniya vakcin. Veterinariya segodnya. 2023; 12(2):164–170. (In Russ). doi: 10.29326/2304-196X-2023-12-2-164-17015

15. Sundaram A, Ewing D, Blevins M, et al. Comparison of purified psoralen-inactivated and formalin-inactivated dengue vaccines in mice and nonhuman primates. Vaccine. 2020; 38(17): 3313–3320. doi: 10.1016/j.vaccine.2020.03.008

16. Amanna I, Raué H, Slifka M. Development of a new hydrogen peroxide–based vaccine platform. Nature medicine. 2012; 18(6): 974–979. doi: 10.1038/nm.2763

17. Abolaban FA, Djouider FM. Gamma irradiation-mediated inactivation of enveloped viruses with conservation of genome integrity: Potential application for SARS-CoV-2 inactivated vaccine development. Open Life Sciences. 2021; 16(1):558–570. doi: 10.1515/biol-2021-0051

18. King AM, Underwood BO, McCahon D, et al. Biochemical identification of viruses causing the 1981 outbreaks of foot and mouth disease in the UK .Nature. 1981; 293(5832): 479–480. doi: 10.1038/293479a0

19. Beck E, Strohmaier K. Subtyping of European foot-and-mouth disease virus strains by nucleotide sequence determination. Journal of virology.1987; 61(5):1621–1629. doi: 10.1128/JVI.61.5

20. Patil PK, Suryanarayana V, Bist P, et al. Integrity of GH-loop of foot-and-mouth disease virus during virus inactivation: detection by epitope specific antibodies. Vaccine. 2002; 20, №. 7-8. P. 1163–1168. doi: 10.1016/s0264-410x(01)00431-5

21. Plotkin SL, Plotkin SA. A short history of vaccination. Vaccines. 2004; 5:1–16. doi: 10.1073/pnas.1400472111

22. Smorodintsev AA, Ilyenko VI. Results of laboratory and epidemiological study of vaccination against tick-borne encephalitis. In: Libíková H Biology of viruses of the tickborne encephalitis complex. Smolenice; 1969:332–343

23. Sanders B, Koldijk M, Schuitemaker H. Inactivated viral vaccines. In: Vaccine analysis: strategies, principles, and control. Berlin: Heidelberg Springer; 2014: 45–80. doi: 10.1007/978-3-662-45024-6_2

24. Sergeev VA, Nepoklonov EA, Aliper TI. Viruses and viral vaccines. M.: Biblioteka; 2007

25. Brown F. Review of accidents caused by incomplete inactivation of viruses. Developments in biological standardization. 1993; 81:103–107.

26. Tkachenko EA. Ishmukhametov AA., Dzagurova TK. et al. Razrabotka ehksperimental’no-promyshlennoj tekhnologii proizvodstva vakciny dlya profilaktiki gemorragicheskoj likhoradki s pochechnym sindromom. Remedium. Zhurnal o rossijskom rynke lekarstv i medicinskoj tekhnike. 2015; 6: 47–54.27. (In Russ).

27. Martín J, Crossland G, Wood DJ, et al. Characterization of formaldehyde-inactivated poliovirus preparations made from live attenuated strains. Journal of general virology. 2003; 84(7): 1781–1788. doi: 10.1099/vir.0.19088-0

28. Bayer L, Fertey J, Ulbert S, et al. Immunization with an adjuvanted low-energy electron irradiation inactivated respiratory syncytial virus vaccine shows immunoprotective activity in mice. Vaccine. 2018; 36 (12): 1561–1569. doi: 10.1016/j.vaccine.2018.02.014

29. Kurashova SS. Ocenka ehffektivnosti ad»yuvantov razlichnogo proiskhozhdeniya, metodov inaktivirovaniya virusov i kontrolya specificheskoj aktivnosti khantavirusnykh vakcinnykh preparatov: [Dissertation]. Moskva; 2021. Available at: https://www.chumakovs.ru/uploads/dissovet/kurashova_disser.pdf. Accessed 13 Oct 2025. (In Russ)

30. Egorova MS, Kurashova SS, Dzagurova TK, et al. Effect of virus-inactivating agents on the immunogenicity of hantavirus vaccines against hemorrhagic fever with renal syndrome. Applied Biochemistry and Microbiology.Biotexnologiya.2020; 56(9): 940–947. (In Russ). doi: 10.21519/0234-2758-2020-36-2-64-73

31. Kurashova SS, Egorova MS, Balovneva MV, et al. Physical and Chemical Inactivators Evaluation for the Puumala Virus Vaccine Technology Development. Epidemiology and Vaccinal Prevention. 2024; 23(4):34–43. (In Russ.) doi: 10.31631/2073-3046-2024-23-4-34-43

32. Srivastava AK, Putnak JR, Lee SH, et al. A purified inactivated Japanese encephalitis virus vaccine made in Vero cells. Vaccine. 2001; 19(31): 4557–4565. doi: 10.1016/s0264-410x(01)00208-0

33. Chumakov MP. L`vov DK., Sarmanova ES., et al. Sravnitel`noe izuchenie e`pidemiologicheskoj e`ffektivnosti privivok kul`tural`noj i mozgovoj vakcinoj protiv kleshhevogo e`ncefalita . Voprosy` virusologii. 1963; 3:307–315. (In Russ)

34. Piniaeva A, Ignatyev G, Kozlovskaya L, et al. Immunogenicity and safety of inactivated Sabin-strain polio vaccine “PoliovacSin”: Clinical trials Phase I and II. Vaccines. 2021; 9(6):565. doi: 10.3390/vaccines9060565

35. Twomey T, Newman J, Burrage T, et al. Structure and immunogenicity of experimental foot-and-mouth disease and poliomyelitis vaccines. Vaccine. 1995; 13(16):1603–1610. doi: 10.1016/0264-410x(95)00079-g

36. Delgado MF, Coviello S, Monsalvo AC, et al. Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease. Nat. Med. 2009; 15(1): 34–41. doi: 10.1038/nm.1894

37. Flipse J, Wilschut J, Smit JM. Molecular mechanisms involved in antibody-dependent enhancement of Dengue virus infection in humans. Traffic. 2013; 14(1): 25–35. doi: 10.1111/tra.12012

38. Offit PA. The Cutter incident, 50 years later. New England Journal of Medicine. 2005; 352(14): 1411–1412. doi: 10.1056/NEJMp048180

39. Cooper CL, Davis HL, Morris ML, et al. Safety and immunogenicity of CPG 7909 injection as an adjuvant to Fluarix influenza vaccine. Vaccine. 2004; 22(23-24):3136–3143. doi: 10.1016/j.vaccine.2004.01.058

40. Reisler RB, Danner DK, Gibbs PH. Immunogenicity of an inactivated Japanese encephalitis vaccine (JE-VAX) in humans over 20 years at USAMRIID: using PRNT50 as an endpoint for immunogenicity. Vaccine. 2010; 28(12):2436–2441. doi: 10.1016/j.vaccine.2009.12.080

41. Fukushima S, Kiyohara T, Ishii K, et al. Immunogenicity of aluminum-adsorbed hepatitis A vaccine (Havrix®) administered as a third dose after primary doses of Japanese aluminum-free hepatitis A vaccine (Aimmugen®) for Japanese travelers to endemic countries. Vaccine. 2017; 35(47): 6412–6415. doi: 10.1016/j.vaccine.2017.10.002

42. Choi Y, Ahn CJ, Seong KM, et al. Inactivated Hantaan virus vaccinederived from suspension culture of Vero cells. Vaccine. 2003:21(17–18):1867–1873. doi: 10.1016/s0264-410x(03)00005-7

43. van Wezel AL, van Steenis G, van der Marel P, et al. Inactivated poliovirus vaccine: current production methods and new developments. Reviews of infectious diseases. 1984:335–340. doi: 10.1093/clinids/6.supplement_2

44. Goncharova E, Ryzhikov E, Poryvaev V, et al. Intranasal immunization with inactivated tick-borne encephalitis virus and the antigenic peptide 89–119 protects mice against intraperitoneal challenge. International Journal of Medical Microbiology. 2006; 296:195–201. doi: 10.1016/j.ijmm.2006.02.002

45. Spravochnik lekarstvenny`x sredstv. Available at: https://www.vidal.ru/. Accessed 6 Oct 2025. (In Russ)

46. Dembinski JL, Hungnes O, Hauge AG.et al. Hydrogen peroxide inactivation of influenza virus preserves antigenic structure and immunogenicity. Journal of virological methods. 2014; 207: 232–237. doi: 10.1016/j.jviromet.2014.07.003

47. David SC, Lau J, Singleton EV, et al. The effect of gamma-irradiation conditions on the immunogenicity of whole-inactivated Influenza A virus vaccine. Vaccine. 2017; 35(7):1071–1079. doi: 10.1016/j.vaccine.2016.12.044

48. McArthur MA, Holbrook MR. Japanese encephalitis vaccines. Journal of bioterrorism & biodefense. 2011: 1002. doi: 10.4172/2157-2526.S1–002

49. Franczuzskaya transnacional`naya farmacevticheskaya kompaniya Sanofi. Available at: https://www.sanofi.com/. Accessed 6 Oct 2025.

50. Shvejczarskaya transnacional`naya farmacevticheskaya kompaniya Novartis. Available at: https://www.novartis.com/. Accessed 6 Oct 2025.

51. Abd-elghaffar AA, Ali AE, Boseila AA, et al. Inactivation of rabies virus by hydrogen peroxide. Vaccine. 2016; 34(6):798–802. doi: 10.1016/j.vaccine.2015.12.041

52. Johnson RF, Kurup D, Hagen KR, et al. An inactivated Rabies virus–based Ebola Vaccine, FILORAB1, adjuvanted with glucopyranosyl lipid A in stable emulsion confers complete protection in nonhuman primate challenge models. The Journal of infectious diseases. 2016; 214(3): 342–354. doi: 10.1093/infdis/jiw231

53. Jin L, Li Z, Zhang X, et al. CoronaVac: A review of efficacy, safety, and immunogenicity of the inactivated vaccine against SARS-CoV-2. Human vaccines & immunotherapeutics. 2022; 18(6):2096970. doi: 10.1080/21645515.2022.2096970

54. Sir Karakus G, Tastan C, Dilek Kancagi D, et al. Preclinical efficacy and safety analysis of gamma-irradiated inactivated SARS-CoV-2 vaccine candidates. Scientific reports. 2021; 11(1): 5804. doi: 10.1038/s41598-021-83930-6

55. Zhugunissov K, Zakarya K, Khairullin B, et al. Development of the inactivated QazCovid-in vaccine: protective efficacy of the vaccine in Syrian hamsters. Frontiers in microbiology. 2021; 12:720437. doi: 10.3389/fmicb.2021

56. Khan A, Shin OS, Na J, et al. A systems vaccinology approach reveals the mechanisms of immunogenic responses to hantavax vaccination in humans. Scientific reports. 2019; 9(1). P: 4760. doi: 10.1038/s41598-019-41205-1

57. Lee HW, Chu YK, Tkachenko E, et al. Vaccines against HFRS. In: Emergence and Control of Rodent-Borne Viral Diseases. France: Elsevier; 1999. P.147–156.

58. Tkachenko EA, Dzagurova TK, Nabatnikov PA. Razrabotka e`ksperimental`noj vakciny` protiv gemorragicheskoj lixoradki s pochechny`m sindromom. Medicinskaya virusologiya. 2009; XXVI: 194–196. (In Russ)

59. Tkachenko EA, Dzagurova TK, Mikhailov MI. Hantavirus strains for manufacturing of vaccine against HFRS. Patent 2423520. 10.07.2011 Available at: https://patents.google.com/patent/RU2423520C1/ru. Accessed: 01.10.2025 (in Russ).

60. Dzagurova TK, Siniugina AA, Ishmukhametov AA, et al. Pre-clinical studies of inactivated polyvalent HFRS vaccine. Frontiers in cellular and infection microbiology. 2020; 10: 545372. doi: 10.3389/fcimb.2020.545372

61. Schmidt AC, Lin L, Martinez LJ, et al. Phase 1 randomized study of a tetravalent dengue purified inactivated vaccine in healthy adults in the United States .The American journal of tropical medicine and hygiene. 2017; 96(6):1325. doi: 10.4269/ajtmh.16-0634

62. Marzi A, Halfmann P, Hill-Batorski L, et al. An Ebola whole-virus vaccine is protective in nonhuman primates. Science. 2015; 348(6233): 439–442. doi: 10.1126/science.aaa4919.

63. Hartman FW, LoGrippo GA. Beta-propiolactone in sterilization of vaccines, tissue grafts, and plasma. Journal of the American Medical Association. 1957; 164(3):258–260. doi: 10.1001/jama

64. Lawrence SA. Beta-propiolactone and aziridine: their applications in organic synthesis and viral inactivation. Chimica oggi. 1999; 17(3-4):51–54.

65. Colburn NH, Richardson RG, Boutwell RK. Studies of the reaction of β-propiolactone with deoxyguanosine and related compounds. Biochemical pharmacology. 1965; 14(7):1113–1118. doi: 10.1016/0006-2952(65)90040-7

66. Mate U, Solomon JJ, Segal A. In vitro binding of β-propiolactone to calf thymus DNA and mouse liver DNA to form 1-(2-carboxyethyl) adenine. Chemico-biological interactions. 1977; 18(3): 327–336. doi: 10.1016/0009-2797(77)90018-7

67. Yang J, Gao J, Zhang Q. Development of gas chromatography for determination of β-propiolactone (BPL) content and analysis of BPL hydrolysis. Chinese Journal of Biologicals. 2010; 3:323–332.

68. Perdiz D, Gróf P, Mezzina M, et al. Distribution and repair of bipyrimidine photoproducts in solar UV-irradiated mammalian cells: possible role of Dewar photoproducts in solar mutagenesis. Journal of Biological Chemistry. 2000; 275(35): 26732–26742. doi: 10.1074/jbc.M001450200

69. Bonnafous P, Nicolaï MC, Taveau JC. Treatment of influenza virus with beta-propiolactone alters viral membrane fusion. Biochimica et Biophysica Acta (BBA)-Biomembranes. 2014; 1838(1): 355–363. doi: 10.1016/j.bbamem

70. Sun Z, Yu Y, Wang W, et al. Studies on the purified inactivated epidemic hemorrhagic fever vaccine. Clinical trial of type 1 EHF vaccine in volunteers. Abstract of 2nd international conference on HFRS, Beijing. 1992. P.109–110.

71. Kozlovskaya LI, Piniaeva AN, Ignatyev GM, Gordeychuk IV, et al. Long-term humoral immunogenicity, safety and protective efficacy of inactivated vaccine against COVID-19 (CoviVac) in preclinical studies. Emerging microbes & infections. 2021; 10(1):1790–1806. doi: 10.1080/22221751.2021.1971569

72. Statler VA, Albano FR, Airey J, et al. Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in children 6–59 months of age: a phase 3, randomized, noninferiority study. Vaccine. 2019; 37(2): 343–351. doi: 10.1016/j.vaccine.2018.07.036

73. Jin L, Li Z, Zhang X, et al. CoronaVac: A review of efficacy, safety, and immunogenicity of the inactivated vaccine against SARS-CoV-2. Human vaccines & immunotherapeutics. 2022; 18(6): 2096970. doi: 10.1080/21645515

74. Valko M, Leibfritz D, Moncol J, et al. Free radicals and antioxidants in normal physiological functions and human disease. The international journal of biochemistry & cell biology. 2007; 39(1): 44–84. doi: 10.1016/j.biocel.2006.07.001

75. Linley E, Denyer S, McDonnell G, et al. Use of hydrogen peroxide as a biocide: new consideration of its mechanisms of biocidal action. Journal of antimicrobial Chemotherapy. 2012; 67(7):1589–1596. doi: 10.1093/jac/dks129

76. Sykes G. Disinfection and Sterilization. 2nd Edition. London: E & F.N. Spon; 1965.

77. Termini J. Hydroperoxide-induced DNA damage and mutations. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2000; 450(1-2):107–124. doi: 10.1016/s0027-5107(00)00019-1

78. Pinto AK, Richner JM, Poore EA, et al. A hydrogen peroxide-inactivated virus vaccine elicits humoral and cellular immunity and protects against lethal West Nile virus infection in aged mice. Journal of virology. 2013; 87(4):1926–1936. doi: 10.1128/JVI.02903-12

79. Poore EA, Slifka DK, Raué HP, et al. Pre-clinical development of a hydrogen peroxide-inactivated West Nile virus vaccine. Vaccine. 2017; 35(2):283–292. doi: 10.1016/j.vaccine.2016.11.080

80. Barrett PN, Terpening SJ, Snow D, et al. Vero cell technology for rapid development of inactivated whole virus vaccines for emerging viral diseases. Expert review of vaccines. 2017; 16(9): 883–894. doi: 10.1080/14760584.2017.1357471

81. Quintel BK, Thomas A, DeRaad DE, et al. Advanced oxidation technology for the development of a next-generation inactivated West Nile virus vaccine. Vaccine. 2019; 37(30): 4214–4221. doi: 10.1016/j.vaccine.2018.12.020

82. Walker JM, Raué HP, Slifka MK. Characterization of CD8+ T cell function and immunodominance generated with an H2O2-inactivated whole-virus vaccine. Journal of virology. 2012; 86(24):13735–13744. doi: 10.1128/JVI.02178-12

83. Wolf AM, Mason J, Fitzpatrick WJ, et al. Ultraviolet irradiation of human plasma to control homologous serum jaundice. Journal of the American Medical Association. 1947; 135 (8): 476–477. doi: 10.1001/jama.1947.02890080006003

84. Mitchell DL. The relative cytotoxicity of (6–4) photoproducts and cyclobutane dimers in mammalian cells. Photochemistry and photobiology. 1988; 48(1):51–57. doi: 10.1111/j.1751-1097.1988.tb02785.x

85. Bennett CJ, Webb M, Willer DO, et al. Genetic and phylogenetic characterization of the type II cyclobutane pyrimidine dimer photolyases encoded by Leporipoxviruses. Virology. 2003; 315(1): 10–19. doi: 10.1016/s0042-6822(03)00512-9

86. Lytle CD, Sagripanti JL. Predicted inactivation of viruses of relevance to biodefense by solar radiation. Journal of virology. 2005; 79(22): 14244–14252. doi: 10.1128/jvi.79.22.14244-14252.2005

87. Cobb TC. UV-C decontamination: NASA, prions, and future perspectives. Applied Biosafety. 2016; 21(2): 84–88. doi: 10.1177/1535676016646217

88. Tseng CC, Li CS. Inactivation of virus-containing aerosols by ultraviolet germicidal irradiation. Aerosol Science and Technology. 2005; 39(12):1136–1142. doi: 10.1080/02786820500428575

89. Miller RL, Plagemann PG. Effect of ultraviolet light on mengovirus: formation of uracil dimers, instability and degradation of capsid, and covalent linkage of protein to viral RNA. Journal of virology. 1974; 13(3): 729–739. doi: 10.1128/JVI.13.3.729-739.1974

90. Subasinghe HA, Loh PC. Reovirus cytotoxicity: some properties of the UV-irradiated reovirus and its capsid proteins. Archiv für die gesamte Virusforschung. 1972; 39(1- 3):172–189. doi: 10.1007/BF01241540

91. Belovickis J, Kurylenka A, Murashko V. Effect of open ultraviolet germicidal irradiation lamps on functionality of excimer lasers used in cornea surgery. International journal of ophthalmology. 2017; 10:1474. doi: 10.18240/ijo.2017.09.22

92. Vaidya V, Dhere R, Agnihotri S, et al. Ultraviolet-C irradiation for inactivation of viruses in foetal bovine serum. Vaccine. 2018; 36(29): 4215–4221.doi: 10.1016/j.vaccine.2018.06.008

93. Prescott J, Ye C, Sen G, et al. Induction of innate immune response genes by Sin Nombre hantavirus does not require viral replication. Journal of virology. 2005; 79(24):15007–15015. doi: 10.1128/jvi.79.24.15007-15015.2005

94. Buranda T, Wu Y, Perez D, et al. Recognition of decay accelerating factor and αvβ3 by inactivated hantaviruses: Toward the development of high-throughput screening flow cytometry assays. Analytical biochemistry. 2010; 402(2):151–160. doi: 10.1016/j.ab.2010.03.016

95. Goldstein M, Tauraso N. Effect of formalin, β-propiolactone, merthiolate, and ultraviolet light upon influenza virus infectivity, chicken cell agglutination, hemagglutination, and antigenicity. Applied Microbiology. 1970; 19(2): 290–294. doi: 10.1128/am.19.2.

96. Henning J, Meers J, Davies PR. Exposure of rabbits to ultraviolet light-inactivated rabbit haemorrhagic disease virus (RHDV) and subsequent challenge with virulent virus. Epidemiology & Infection. 2005; 133(4): 731–735. doi: 10.1017/s0950268805003754

97. Sarzotti M, Dean TA, Remington M, et al. Ultraviolet-light-inactivated Cas-Br-M murine leukemia virus induces a protective CD8+ cytotoxic T lymphocyte response in newborn mice. AIDS research and human retroviruses. 1994; 10(12):1695–1702. doi: 10.1089/aid.1994.10.1695

98. Vanhee M, Delputte PL, Delrue I, et al. Development of an experimental inactivated PRRSV vaccine that induces virus-neutralizing antibodies. Veterinary research. 2009; 40(6). doi: 10.1051/vetres/2009046

99. Caillet-Fauquet P, Giambattista Di, Draps M, et al. Continuous-flow UVC irradiation: a new, effective, protein activity-preserving system for inactivating bacteria and viruses, including erythrovirus B19. Journal of virological methods. 2004; 118(2):131–139. doi: 10.1016/j.jviromet.2004.02.002

100. Wang J, Mauser A, Chao S, et al. Virus inactivation and protein recovery in a novel ultraviolet‐C reactor. Vox sanguinis. 2004; 86(4):230–238. doi: 10.1111/j.0042-9007.2004.00485.x

101. Petricciani J, Sheets R, Griffiths A, et al. Adventitious agents in viral vaccines: lessons learned from 4 case studies. Biologicals. 2014; 42(5):223–236. doi:10.1016/j.biologicals.2014.07.003

102. Burke M, Augenstein L. A comparison of the effects of ultraviolet and ionizing radiations on trypsin activity and on its constituent amino acids. Biochemical Journal. 1969; 114(3): 535–545. doi: 10.1042/bj1140535

103. Solov`ev AG, Vorob`eva IV, Sidorova OP. E`pidemiologiya i profilaktika beshenstva v Rossii: rol` vakciny` Kokav. Medicinskaya mikrobiologiya i immunologiya. 2019; 3:34–39. (In Russ).

104. Nims RW, Gauvin G, Plavsic M. Gamma irradiation of animal sera for inactivation of viruses and mollicutes–a review. Biologicals. 2011; 39(6): 370–377. doi: 10.1016/j.biologicals.2011.05.003

105. Sabbaghi A, Miri SM, Keshavarz M, et al. Inactivation methods for whole influenza vaccine production. Reviews in medical virology. 2019; 29(6): 2074. doi: 10.1002/rmv.2074. Epub 2019 Jul 23

106. Smolko EE, Lombardo JH. Virus inactivation studies using ion beams, electron and gamma irradiation. Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms. 2005; 236(1-4): 249–253.

107. McCormick JB, Mitchell SW, Kiley MP, et al. Inactivated Lassa virus elicits a non-protective immune response in rhesus monkeys. Journal of medical virology. 1992; 37(1):1– 7. doi: 10.1002/jmv.1890370102

108. Magsumov RZ. Razrabotka texnologii izgotovleniya radioinaktivirovannoj vakciny` Gammavak-VNIVI protiv bolezni Aueski (psevdobeshenstva) i izuchenie ee e`ffektivnosti v proizvodstvenny`x usloviyax: [Dissertation]. Kazan`; 2004. Available at: https://www.dissercat.com/content/razrabotka-tekhnologii-izgotovleniya-radioinaktivirovannoi-vaktsiny-gammavak-vnivi-protiv-bo?ysclid=mi4fdhxiqb736436664. Accessed: 12 Oct 2025. (In Russ).

109. David SC, Lau J, Singleton EV, et al. The effect of gamma-irradiation conditions on the immunogenicity of whole-inactivated Influenza A virus vaccine. Vaccine. 2017; 35(7): 1071–1079. doi: 10.1016/j.vaccine.2016.12.044

110. Marennikova SS, Macevič GR. Experimental study of the role of inactivated vaccine in two-step vaccination against smallpox. Bulletin of the World Health Organization. 1975; 52(1): 51.

111. Elliott LH, McCormick JB, Johnson K.M. Inactivation of Lassa, Marburg, and Ebola viruses by gamma irradiation. Journal of Clinical Microbiology. 1982; 16(4):704–708. doi: 10.1128/jcm.16.4.704-708.1982

112. Furuya Y, Regner M, Lobigs M, et al. Effect of inactivation method on the cross-protective immunity induced by whole ‘killed’influenza A viruses and commercial vaccine preparations. Journal of General Virology. 2010; 91(6): 1450–1460. doi: 10.1099/vir.0.018168-0

113. Grieb T, Forng RY, Brown R, et al. Effective use of gamma irradiation for pathogen inactivation of monoclonal antibody preparations. Biologicals. 2002; 30(3): 207–216. doi: 10.1006/biol.2002.0330

114. Hanson CV, Riggs JL, Lennette EH. Photochemical inactivation of DNA and RNA viruses by psoralen derivatives. J Gen Virol. 1978; 40: 345–358. doi: 10.1099/0022-1317-40-2-345

115. Groene WS, Shaw RD. Psoralen preparation of antigenically intact noninfectious rotavirus particles. Journal of virological methods. 1992; 38(1): 93–102. doi:10.1016/0166-0934(92)90172-a

116. Hanson CV. Inactivation of viruses for use as vaccines and immunodiagnostic reagents. Medical Virology II Elsevier. 1983: 45–79.

117. Sutjipto S, Pedersen NC, Miller CJ, et al. Inactivated simian immunodeficiency virus vaccine failed to protect rhesus macaques from intravenous or genital mucosal infection but delayed disease in intravenously exposed animals. Journal of virology. 1990; 64(5): 2290–2297. doi: 10.1128/JVI.64.5.2290-2297.1990

118. Watson AJ, Klanieki J, Hanson CV. Psoralen/UV inactivation of HIV-1-infected cells for use in cytologic and immunologic procedures. AIDS research and human retroviruses. 1990; 6(4): 503–513. doi: 10.1089/aid.1990.6.503

119. Wong ML, Hsu MT. Psoralen-cross-linking study of the organization of intracellular adenovirus nucleoprotein complexes. Journal of virology. 1988; 62(4): 1227–1234. doi: 10.1128/JVI.62.4.1227-1234.1988

120. Swanstrom R, Hallick LM, Jackson J, et al. Interaction of psoralen derivatives with the RNA genome of Rous sarcoma virus. Virology. 1981; 113(2): 613–622. doi: 10.1016/0042-6822(81)90189-6

121. Maves RC, Castillo Oré RM, Porter KR, et al. Immunogenicity of a psoralen-inactivated dengue virus type 1 vaccine candidate in mice. Clinical and Vaccine Immunology. 2010;17(2): 304–306. doi: 10.1128/CVI.00353-09353-09


Review

For citations:


Egorova M.S., Kurashova S.S., Vetrova A.N., Dzagurova T.K. Methods for Virus Inactivation in the Production Technology of Whole Virion Vaccines. Epidemiology and Vaccinal Prevention. 2025;24(6):77-91. (In Russ.) https://doi.org/10.31631/2073-3046-2025-24-6-77-91

Views: 29


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2073-3046 (Print)
ISSN 2619-0494 (Online)