Route-coupled pathogenicity and immunogenicity of vaccinia virus variant inoculated mice

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Abstract

Vaccinia virus had played a key role in the global smallpox eradication. However, in case of mass vaccination with various Vaccinia virus strains severe side effects were revealed sometimes ending up with lethal outcomes, especially in immunocompromised humans. Hence, in 1980 the World Health Organization recommended to cancel smallpox vaccination after declaring about smallpox eradication. Over the last 40 years, human population virtually lost immunity not only against smallpox, but also against other zoonotic orthopoxvirus infections, such as monkeypox, cowpox, buffalopox, and camelpox. All of them pose a represent increasing threat to human health and heighten a risk of emerging highly contagious viruses due to natural evolution of previous zoonotic orthopoxviruses. In order to prevent development of small outbreaks into spreading epidemics and, thus, to decrease a risk of emergence due to natural evolution of highly pathogenic for humans orthopoxviruses, efforts should be applied to develop safe new generation live vaccines based on Vaccinia virus with target virulence genes inactivation. These strains should be examined in laboratory animal models inoculated via different routes. Currently, Vaccinia virus often becomes attenuated to create live recombinant vaccines due to inserting target DNA sequences into the virus virulence genes resulting in their inactivation. Vaccinia virus strain LIVP used in the Russian Federation as smallpox vaccine as well as derivative attenuated variant LIVP-GFP created by using genetic engineering methods with inactivating its thymidine kinase gene were examined. Such viruses were intracerebrally inoculated into suckling mice at doses of 101 or 102 PFU/animal for neurovirulence assessment. Adult mice were infected intranasally, subcutaneously or intradermally at doses of 107 or 108 PFU/animal and clinical manifestations were analyzed for 14 days. On the 28th day after the onset, blood serum samples were collected from individual mice to measure virus specific antibody level by using ELISA. It was shown that recombinant Vaccinia virus strain LIVP-GFP displayed markedly lowered neurovirulence and pathogenicity for mice as compared to parental LIVP. Finally, intradermal route turned out to demonstrate the most safe and effective profile for immunization with both examined Vaccinia virus strains.

About the authors

S. N. Shchelkunov

State Research Center of Virology and Biotechnology VECTOR

Author for correspondence.
Email: snshchel@vector.nsc.ru
ORCID iD: 0000-0002-6255-9745

Sergei N. Shchelkunov - PhD, MD (Biology), Professor, Head Researcher, Department of Genomic Research, SRC VB VECTOR.

630559, Novosibirsk Region, Koltsovo.

Phone: +7 (903) 939-94-80 (mobile); Fax: +7 (383) 336-74-09

Russian Federation

A. A. Sergeev

State Research Center of Virology and Biotechnology VECTOR

Email: sergeev_ala@vector.nsc.ru

PhD (Biology), Leading Researcher, Department of Microorganisms Collection, SRC VB VECTOR.

630559, Novosibirsk Region, Koltsovo.

Russian Federation

A. S. Kabanov

State Research Center of Virology and Biotechnology VECTOR

Email: kabanov_as@vector.nsc.ru

PhD (Biology), Senior Researcher, Department of Microorganisms Collection, SRC VB VECTOR.

630559, Novosibirsk Region, Koltsovo.

Russian Federation

S. N. Yakubitskyi

State Research Center of Virology and Biotechnology VECTOR

Email: yakubitskiy_sn@vector.nsc.ru

Junior Researcher, Department of Genomic Research, SRC VB VECTOR.

630559, Novosibirsk Region, Koltsovo.

Russian Federation

T. V. Bauer

State Research Center of Virology and Biotechnology VECTOR

Email: bauer_tv@vector.nsc.ru

Junior Researcher, Department of Genomic Research, SRC VB VECTOR.

630559, Novosibirsk Region, Koltsovo.

Russian Federation

S. A. Pyankov

State Research Center of Virology and Biotechnology VECTOR

Email: piankov_sa@vector.nsc.ru

Leading Researcher, Department of Microorganisms Collection, SRC VB VECTOR.

630559, Novosibirsk Region, Koltsovo.

Russian Federation

References

  1. Ашмарин И.П., Воробьев А.А. Статистические методы в микробиологических исследованиях. Л.: Медгиз, 1962. 182 с.
  2. Щелкунов С.Н., Щелкунова Г.А. Нужно быть готовыми к возврату оспы // Вопросы вирусологии. 2019. Т. 64, № 5. С. 206-214. doi: 10.36233/0507-4088-2019-64-5-206-214
  3. Downie A.W. The immunological relationship of the virus of spontaneous cowpox to vaccinia virus. Br. J. Exp. Pathol., 1939, vol. 20, pp. 158-176.
  4. Fenner F., Henderson D.A., Arita I., Jezek Z., Ladnyi I.D. Smallpox and its eradication. Geneva: WHO, 1988. 1460 p.
  5. Jacobs B.L., Langland J.O., Kibler K.V., Denzler K.L., White S.D., Holechek S.A., Wong S., Huynh T., Baskin C.R. Vaccinia virus vaccines: past, present and future. Antiviral Research, 2009, vol. 84, pp. 1-13. doi: 10.1016/j.antiviral.2009.06.006
  6. Kretzschmar M., Wallinga J., Teunis P., Xing S., Mikolajczyk R. Frequency of adverse events after vaccination with different vaccinia strains. PLoS Med., 2006, vol. 3, no. 8: e272. doi: 10.1371/journal.pmed.0030272
  7. Lee M.S., Roos J.M., McGuigan L.C., Smith K.A., Cormier N., Cohen L.K., Roberts B.E., Payne L.G. Molecular attenuation of vaccinia virus: mutant generation and animal characterization. J. Virol., 1992, vol. 66, no. 5, pp. 2617-2630.
  8. Manjaly Thomas Z.-R., Satti I., Marshall J.L., Harris S.A., Lopez Ramon R., Hamidi A., Minhinnick A., Riste M., Stockdale L., Lawrie A.M., Vermaak S., Wilkie M., Bettinson H., McShane H. Alternate aerosol and systemic immunization with a recombinant viral vector for tuberculosis, MVA85A: a phase I randomised controlled trial. PLoS Med., 2019, vol. 16, no. 4: e1002790. doi: 10.1371/journal.pmed.1002790
  9. McClain D.J., Harrison S., Yeager C.L., Cruz J., Ennis F.A., Gibbs P., Wright M.S., Summers P.L., Arthur J.D., Graham J.A. Immunologic responses to vaccinia vaccines administered by different parenteral routes. J. Infect. Dis., 1997, vol. 175, no. 4, pp. 756-763.
  10. McIntosh A.A.G., Smith G.L. Vaccinia virus glycoprotein A34R is required for infectivity of extracellular enveloped virus. J. Virol., 1996, vol. 70, no. 1, pp. 272-281.
  11. Olson V.A., Shchelkunov S.N. Are we prepared in case of a possible smallpox-like disease emergence? Viruses, 2017, vol. 9: e242. doi: 10.3390/v9090242
  12. Paran N., Lustig S., Zvi A., Erez N., Israely T., Melamed S., Politi B., Ben-Nathan D., Schneider P., Lachmi B., Israeli O., Stein D., Levin R., Olshevsky U. Active vaccination with vaccinia virus A33 protects mice against lethal vaccinia and ectromelia viruses but not against cowpox virus; elucidation of the specific adaptive immune response. Virol. J., 2013, vol. 10: 229. doi: 10.1186/1743-422X-10-229
  13. Petrov I.S., Goncharova E.P., Pozdnyakov S.G., Shchelkunov S.N., Zenkova M.A., Vlasov V.V., Kolosova I.V. Antitumor effect of the LIVP-GFP recombinant vaccinia virus. Dokl. Biol. Sci., 2013, vol. 451, no. 1, pp. 248-252. doi: 10.1134/S0012496613040133
  14. Roy S., Jaeson M.I., Li Z., Mahboob S., Jackson R.J., Grubor-Bauk B., Wijesundara D.K., Gowans E.J., Ranasinghe C. Viral vector and route of administration determine the ILC and DC profiles responsible for downstream vaccine-specific immune outcomes. Vaccine, 2019, vol. 37, pp. 1266-1276. doi: 10.1016/j.vaccine.2019.01.045
  15. Shchelkunov S.N. An increasing danger of zoonotic orthopoxvirus infections. PLoS Pathog., 2013, vol. 9: e1 003 75 6. doi: 10.1371/journal.ppat.1003756
  16. Shchelkunov S.N. Emergence and reemergence of smallpox: the need in development of a new generation smallpox vaccine. Vaccine, 2011, vol. 29S, pp. D49-D53. doi: 10.1016/j.vaccine.2011.05.037
  17. Shchelkunov S.N., Marennikova S.S., Moyer R.W. Orthopoxviruses pathogenic for humans. New York: Springer, 2005. 425 p.
  18. Shchelkunov S.N., Nesterov A.E., Ryazankin I.A., Ignat'ev G.M., Sandakhchiev L.S. Development of a candidate polyvalent live vaccine against human immunodeficiency, hepatitis B, and orthopoxviruses. Doklady Biochemistry and Biophysics, 2003, vol. 390, no. 1-6, pp. 180-183.
  19. Shchelkunova G.A., Shchelkunov S.N. 40 years without smallpox. Acta Naturae, 2017, vol. 9, no. 4, pp. 4-12.
  20. Sklenovska N., Van Ranst M. Emergence of monkeypox as the most important orthopoxvirus infection in humans. Front. Public Health, 2018, vol. 6: e241. doi: 10.3389/fpubh.2018.00241
  21. Xie L., Zai J., Yi K., Li Y. Intranasal immunization with recombinant vaccinia virus Tiantan harboring Zaire Ebola virus gp elicited systemic and mucosal neutralizing antibody in mice. Vaccine, 2019, vol. 37, pp. 3335 -3342. doi: 10.1016/j.vaccine.2019.04.070
  22. Yakubitskiy S.N., Kolosova I.V., Maksyutov R.A., Shchelkunov S.N. Attenuation of vaccinia virus. Acta Naturae, 2015, vol. 7, no. 4, pp. 113-121.

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Copyright (c) 2020 Shchelkunov S.N., Sergeev A.A., Kabanov A.S., Yakubitskyi S.N., Bauer T.V., Pyankov S.A.

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