Comparative analysis of residual neurovirulence of vaccine and low attenuated rubella virus (Matonaviridae: Rubivirus: Rubella virus) strains in the experiments on the macaque rhesus (Macaca mulatta) monkeys

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Abstract

Introduction. Rubella is currently an infection controlled by specific prophylaxis. Not only the right vaccine prophylaxis strategy and tactics, but also the use of effective and safe vaccine preparations is crucial for the elimination of this disease.

The aim of the investigation was to study the morphological and pathogenetic patterns of changes developing in the central nervous system (CNS) and internal organs of monkeys (Haplorhini) during intracerebral inoculation with 2 strains of rubella virus (Matonaviridae: Rubivirus: Rubella virus) (RV): highly attenuated Orlov-B, and low attenuated Orlov-14.

Material and methods. In the experiments, seronegative rhesus macaque monkeys (Macaca mulatta) weighing 3.3–5.1 kg (n = 7) were used. Neurovirulence of the strains was determined by a complex of clinical, pathomorphological, and virological methods.

Results and discussion. It was found that during attenuation, the Orlov-B strain lost the ability to replicate in CNS cells and induce moderate/expressed specific changes in them, as well as to overcome the blood-brain barrier and cause the damage of sensitive organs and tissues. This fact indicates a low level of residual neurovirulence of the vaccine strain.

Conclusion. The results obtained in this study regarding the clinical symptoms of CNS lesions and the nature of the pathological process in its tissues in experimental animals can be significant for the improvement of safety control of live rubella vaccines. These data indicate that the Orlov-B strain can be considered as a candidate strain for further study on the development of a rubella vaccine based on the domestic vaccine strain.

About the authors

O. A. Shamsutdinova

FSBRI «Research Institute of Medical Primatology» of the Ministry of Education and Science of Russia

Author for correspondence.
Email: shamsutdinova-o-a@yandex.ru
ORCID iD: 0000-0002-2742-3965

Olga Anatolyevna Shamsutdinova, scientist, lab. immunology and cell biology 

177 Mira str., Veseloe village, Sochi, Adler, 354376

Россия

D. V. Bulgin

FSBRI «Research Institute of Medical Primatology» of the Ministry of Education and Science of Russia

Email: molmed1999@yahoo.com
ORCID iD: 0000-0003-1739-8505

Dmitriy Viktorovich Bulgin - Ph.D. head of laboratory of pathological anatomy 

177 Mira str., Veseloe village, Sochi, Adler, 354376

Россия

D. D. Karal-ogly

FSBRI «Research Institute of Medical Primatology» of the Ministry of Education and Science of Russia

Email: karal_5@mail.ru
ORCID iD: 0000-0003-3606-1668

Dgina Dginarovna Karal-ogly - Ph.D. depute of director 

177 Mira str., Veseloe village, Sochi, Adler, 354376

Россия

I. N. Lavrentieva

FSBI «Saint Petersburg Pasteur Research Institute of Epidemiology and Microbiology» of the Federal Service
for Surveillance on Consumer Rights Protection and Human Welfare (Rospotrebnadzor)

Email: pasteur.lawr@mail.ru
ORCID iD: 0000-0002-2188-6547

Irina Nikolaevna Lavrent'eva - Ph.D. Doctor of medical Sciences, head of laboratory of experimental virology 

14 Mira str., Saint Petersburg, 197101

Россия

I. N. Klots

FSBRI «Research Institute of Medical Primatology» of the Ministry of Education and Science of Russia

Email: igor-imp@mail.ru
ORCID iD: 0000-0003-1025-3127

Igor Naumovich Klots - Ph.D. head of laboratory of immunology and cell biology 

177 Mira str., Veseloe village, Sochi, Adler, 354376

Россия

References

  1. Bouthry E., Picone O., Hamdi G., Grangeot-Keros L., Ayoubi J.M., Vauloup-Fellous C. Rubella and pregnancy: diagnosis, management and outcomes. Prenat. Diagn. 2014; 34(13): 1246–53. https://doi.org/10.1002/pd.4467
  2. Saffar H., Khalifeloo M., Saffar M.J., Abdollahi A., Parsaei M.R., Ghorbani G.R., et al. Measles and rubella serosusceptibity among population vaccinated with different schedules: the potential impact on measles-rubella elimination in Iran. BMC Infect. Dis. 2021; 21(1): 305. https://doi.org/10.1186/s12879-021-05970-7
  3. Di Pietrantonj C., Rivetti A., Marchione P., Debalini M.G., Demicheli V. Vaccines for measles, mumps, rubella, and varicella in children. Cochrane Database Syst. Rev. 2020; 4(4): CD004407. https://doi.org/10.1002/14651858.CD004407.pub4
  4. Terracciano E., Amadori F., Pettinicchio V., Zaratti L., Franco E. Strategies for elimination of rubella in pregnancy and of congenital rubella syndrome in high and upper-middle income countries. J. Prev. Med. Hyg. 2020; 61(1): E98-E108. https://doi.org/10.15167/2421-4248/jpmh2020.61.1.1310
  5. Croce E., Hatz C., Jonker Е.F., Visser L.G., Jaeger V.K., Bühler S. Safety of live vaccinations on immunosuppressive therapy in patients with immune-mediated inflammatory diseases, solid organ transplantation or after bone-marrow transplantation – A systematic review of randomized trials, observational studies and case reports. Vaccine. 2017; 35(9): 1216–26. https://doi.org/10.1016/j.vaccine.2017.01.048
  6. Миронов А.Н., ред. Руководство по проведению доклинических исследований лекарственных средств. Том 1. М.: Гриф и К; 2012.
  7. Yang M.H., Freitas A.R.R. Biological view of vaccination described by mathematical modellings: from rubella to dengue vaccines. Math. Biosci. Eng. 2019; 16(4): 3195–214. https://doi.org/10.3934/mbe.2019159
  8. Мешалова В.Н., Жукова Е.А., Степанов А.Н. Прививочные свойства краснушной вакцины из штамма «Орлов». В кн.: Детские вирусные инфекции: Труды Института Пастера. Ленинград; 1979: 112–5.
  9. Медуницын Н.В. Государственная система оценки безопасности вакцин. Вакцинация. Новости вакцинопрофилактики: информационный бюллетень. 2000; (8): 4–6.
  10. Лаврентьева И.Н., Сухобаевская Л.П., Жебрун А.Б. Штамм вируса краснухи для получения медицинских иммунобиологических препаратов (МИБП). Патент РФ № 2081912; 1995. Available at: https://www.freepatent.ru/patents/2492235.
  11. Общая фармакопейная статья ОФС.1.7.2.0010.15. Оценка специфической безопасности производственных штаммов и посевных вирусов кори, паротита и краснухи. Available at: https://nevacert.ru/reestry/pharmacopoeia/ofs.1.7.2.0010.15 (accessed February 2, 2022).
  12. Barrett J.R. Pediatric vaccines and neurodevelopment: primate study finds no adverse behavioral effects. Environ. Health Perspect. 2015; 123(6): A156. https://doi.org/10.1289/ehp.123-A156
  13. Curtis В., Liberato N., Rulien M., Morrisroe K., Kenney C., Yutuc V., et al. Examination of the safety of pediatric vaccine schedules in a non-human primate model: assessments of neurodevelopment, learning, and social behavior. Environ. Health Perspect. 2015; 123(6): 579–89. https://doi.org/10.1289/ehp.1408257
  14. Gadad B.S., Li W., Yazdani U., Grady S., Johnson T., Hammond J., et al. Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology. Proc. Natl. Acad. Sci. USA. 2015; 112(40): 12498– 503. https://doi.org/10.1073/pnas.1500968112
  15. Lapin B.A., Shevtsova Z.V. Monkey viral pathology in the Sukhum colony and modeling human viral infections. J. Med. Primatol. 2018; 47(4): 273–7. https://doi.org/10.1111/jmp.12351
  16. Lim F.S., Han H.H., Bock H.L. Safety, reactogenicity and immunogenicity of the live attenuated combined measles, mumps and rubella vaccine containing the RIT 4385 mumps strain in healthy Singaporean children. Ann. Acad. Med. Singap. 2007; 36(12): 969–73.

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Copyright (c) 2022 Shamsutdinova O.A., Bulgin D.V., Karal-ogly D.D., Lavrentieva I.N., Klots I.N.

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