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Varicella and Herpes zoster vaccines: from live attenuated vaccines to genetically engineered products

https://doi.org/10.30895/2221-996X-2025-645

Abstract

INTRODUCTION. Varicella zoster virus remains a serious threat to public health and is a significant burden on the health system due to treatment costs. Vaccination coverage against varicella zoster (VZ) and herpes zoster (HZ) remains low for a number of reasons, including lack of sufficient vaccines. Improving the existing vaccines, creating new genetically engineered, effective products with a high safety profile, and updating their assessment protocols (including cellular immune response parameters in the algorithms) is a prerequisite for further vaccine prevention of diseases caused by high-risk factors. Systematising status of VZ and HZ vaccines will help developers enhance preclinical and clinical research protocols.

AIM. This study aimed to analyse the experience of developing and introducing modern vaccines to prevent diseases caused by varicella virus, as well as assessing the ways of further developments of preventive vaccines.

DISCUSSION. Live vaccines are recommended for prevention of VZ and HZ, as they mimic the body’s natural immune response to a viral agent and activate both humoral and cellular immune responses. To date, seven live vaccines for VZ prevention and two live vaccines for HZ prevention are registered worldwide. However, under conditions of reduced immunity, live vaccines are not recommended due to high risk of vaccine-associated diseases. A recombinant glycoprotein E (gpE)-based vaccine with adjuvant system is indicated for HZ prevention in people over 50 years and allowed in immunocompromised patients.

CONCLUSIONS. Research of vaccine development based on recombinant, RNA and DNA technologies shows the best prospects, since their safety is superior to live vaccines in a number of parameters and they can be used in immunocompromised patients. Both live attenuated and recombinant vaccines against diseases associated with the varicella virus are under development in Russia.

About the Authors

A. V. Zotova
I. Mechnikov Research Institute of Vaccines and Sera
Russian Federation

Anna V. Zotova, Cand. Sci. (Pharm.)

5A/2 Maly Kazenny Ln., Moscow 105064



O. A. Svitich
I. Mechnikov Research Institute of Vaccines and Sera; I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Oxana A. Svitich, Dr. Sci. (Med.), Prof., Acad. RAS

5A/2 Maly Kazenny Ln., Moscow 105064; 
8/2 Trubetskaya St., Moscow 119991



References

1. Rudakova AV, Kharit SM, Babachenko IV, et al. Cost effectiveness analysis of universal varicella vaccination in the Russian Federation. Journal Infectology. 2021;13(3):114–9 (In Russ.). https://doi.org/10.22625/2072-6732-2021-13-3-114-119

2. Arvin АМ, Moffat JF, Abendroth A, Oliver SL. Varicella-zoster virus. Genetics, pathogenesis and immunity. Springer Cham; 2023. https://doi.org/10.1007/978-3-031-15305-1

3. Sauerbrei A, Wutzler P. Herpes simplex and varicella-zoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Part 2: Varicella-zoster virus infections. Med Microbiol Immunol. 2007;196(2):95–102. https://doi.org/10.1007/s00430-006-0032-z

4. Schmidt-Chanasit J, Sauerbrei A. Evolution and world-wide distribution of varicella-zoster virus clades. Infect Genet Evol. 2011;11(1):1–10. https://doi.org/10.1016/j.meegid.2010.08.014

5. Johnson RW, Wasner G, Saddier P, Baron R. Herpes zoster and postherpetic neuralgia: optimizing management in the elderly patient. Drugs Aging. 2008;25(12):991–1006. https://doi.org/10.2165/0002512-200825120-00002

6. Forbes HJ, Thomas SL, Smeeth L, et al. A systematic review and meta-analysis of risk factors for postherpetic neuralgia. Pain. 2016;157(1):30–54. https://doi.org/10.1097/j.pain.0000000000000307

7. Johnson RW, Rice AS. Clinical practice. Postherpetic neuralgia. N Engl J Med. 2014;371(16):1526–33. https://doi.org/10.1056/NEJMcp1403062

8. Huerta MÁ, Garcia MM, García-Parra B, et al. Investigational drugs for the treatment of postherpetic neuralgia: Systematic review of randomized controlled trials. Int J Mol Sci. 2023;24(16):12987. https://doi.org/10.3390/ijms241612987

9. Prikhodchenko NG. Varicella-pox virus infection: features of the course, clinical manifestations, complications, and possibilities for prevention. Therapeutic Archive. 2021;93(11):1401–6 (In Russ.). https://doi.org/10.26442/00403660.2021.11.201192

10. Isagulyan ED, Semenov DE, Tomskiy AA. Neurosurgical treatment of postherpetic neuralgia. S.S. Korsakov Journal of Neurology and Psychiatry. 2024;124(2):154–7 (In Russ.). https://doi.org/10.17116/jnevro2024124021154

11. Davis AR, Sheppard J. Herpes zoster ophthalmicus review and prevention. Eye Contact Lens. 2019;45(5):286–91. https://doi.org/10.1097/ICL.0000000000000591

12. Kedar S, Jayagopal LN, Berger JR. Neurological and ophthalmological manifestations of varicella zoster virus. J Neuroophthalmol. 2019;39(2):220–31. https://doi.org/10.1097/WNO.0000000000000721

13. Curhan SG, Kawai K, Yawn B, et al. Herpes zoster and long-term risk of cardiovascular disease. J Am Heart Assoc. 2022;11(23):e027451. https://doi.org/10.1161/JAHA.122.027451

14. Bakradze E, Esenwa CC, Schmid DS, et al. Cross-sectional retrospective study to identify clinical and radiographic features associated with VZV reactivation in cryptogenic stroke patients with CSF testing. Neurohospitalist. 2022;12(3):437–43. https://doi.org/10.1177/19418744221075123

15. Wu H, Li J, Wang R, et al. A case of ischemic stroke secon dary to varicella-zoster virus meningoencephalitis. J Neurovirol. 2022;28(2):319–21. https://doi.org/10.1007/s13365-022-01050-x

16. Lecrenier N, Beukelaers P, Colindres R, et al. Development of adjuvanted recombinant zoster vaccine and its implications for shingles prevention. Expert Rev Vaccines. 2018;17(7):619–34. https://doi.org/10.1080/14760584.2018.1495565

17. Chaves SS, Haber P, Walton K, et al. Safety of varicella vaccine after licensure in the United States: Experience from reports to the vaccine adverse event reporting system, 1995–2005. J Infect Dis. 2008;197(Suppl 2):S170–7. Erratum in: J Infect Dis. 2014;210(12):2021. https://doi.org/10.1086/522161

18. Davidson N, Broom J. Vaccine strain varicella zoster virus transmitted within a family from a child with shingles results in varicella meningitis in an immunocompetent adult. Intern Med J. 2019;49(1):132–3. https://doi.org/10.1111/imj.14178

19. Tseng HF, Schmid DS, Harpaz R, et al. Herpes zoster caused by vaccine-strain varicella zoster virus in an immunocompetent recipient of zoster vaccine. Clin Infect Dis. 2014;58(8):1125–8. https://doi.org/10.1093/cid/ciu058

20. Quinlivan M, Breuer J. Clinical and molecular aspects of the live attenuated Oka varicella vaccine. Rev Med Virol. 2014;24(4):254–73. https://doi.org/10.1002/rmv.1789

21. Choi UY, Kim KH, Lee J, et al. Immunogenicity and safety profiles of a new MAV/06 strain varicella vaccine in healthy children: A multinational, multicenter, randomized, double-blinded, active-controlled phase III study. Vaccine. 2021;39(12):1758–64. https://doi.org/10.1016/j.vaccine.2021.02.013

22. Pan CX, Lee MS, Nambudiri VE. Global herpes zoster incidence, burden of disease, and vaccine availability: A narrative review. Ther Adv Vaccines Immunother. 2022;10:25151355221084535. https://doi.org/10.1177/25151355221084535

23. Choi UY, Kim KH, Cho HK, et al. Immunogenicity and safety of a newly developed live attenuated varicella vaccine in healthy children: A multi-national, randomized, double-blinded, active-controlled, phase 3 study. Vaccines (Basel). 2023;11(9):1416. https://doi.org/10.3390/vaccines11091416

24. Lee YH, YJ Choe, Lee J, et al. Global varicella vaccination programs. Clin Exp Pediatr. 2022;65(12):555–62. https://doi.org/10.3345/cep.2021.01564

25. Depledge DP, Yamanishi K, Gomi Y, et al. Deep sequencing of distinct preparations of the live attenuated varicella-zoster virus vaccine reveals a conserved core of attenuating single-nucleotide polymorphisms. J Virol. 2016;90(19):8698–704. https://doi.org/10.1128/JVI.00998-16

26. Moon JY, Seo J, Lee J, Park D. Assessment of attenuation of varicella-zoster virus vaccines based on genomic comparison. J Med Virol. 2023;95(3):e28590. https://doi.org/10.1002/jmv.28590

27. Marin M, Leung J, Gershon AA. Transmission of vaccine-strain varicella-zoster virus: A systematic review. Pediatrics. 2019;144(3):e20191305. https://doi.org/10.1542/peds.2019-1305

28. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352(22):2271–84. https://doi.org/10.1056/NEJMoa051016

29. Harbecke R, Cohen JI, Oxman MN. Herpes zoster vaccines. J Infect Dis. 2021;224(12 Suppl 2):S429–42. https://doi.org/10.1093/infdis/jiab387

30. Choi WS, Choi JH, Jung DS, et al. Immunogenicity and safety of a new live attenuated herpes zoster vaccine (NBP608) compared to Zostavax® in healthy adults aged 50 years and older. Vaccine. 2019;37(27):3605–10. https://doi.org/10.1016/j.vaccine.2019.04.046

31. Cunningham AL, Levin MJ. Herpes zoster vaccines. J Infect Dis. 2018;218(Suppl 2):S127–33. https://doi.org/10.1093/infdis/jiy382

32. Thompson MA, Horberg MA, Agwu AL, et al. Primary care guidance for persons with human immunodeficiency virus: 2020 update by the HIV medicine association of the infectious diseases society of America. Clin Infect Dis. 2021;73(11):e3572–605. https://doi.org/10.1093/cid/ciaa1391 Erratum in: Clin Infect Dis. 2022;74(10):1893–98. https://doi.org/10.1093/cid/ciab801 Erratum in: Clin Infect Dis. 2022;75(11):2052. https://doi.org/10.1093/cid/ciac474

33. Furer V, Rondaan C, Heijstek MW, et al. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2020;79(1):39–52. https://doi.org/10.1136/annrheumdis-2019-215882

34. Mullane KM, Winston DJ, Wertheim MS, et al. Safety and immunogenicity of heat-treated zoster vaccine (ZVHT) in immunocompromised adults. J Infect Dis. 2013;208(9):1375–85. https://doi.org/10.1093/infdis/jit344

35. Winston DJ, Mullane KM, Cornely OA, et al. V212 protocol 001 trial team. Inactivated varicella zoster vaccine in autologous haemopoietic stem-cell transplant recipients: an international, multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2018;391(10135):2116–27. https://doi.org/10.1016/S0140-6736(18)30631-7

36. Wang W, Pan D, Fu W, et al. Development of a skin- and neuro-attenuated live vaccine for varicella. Nat Commun. 2022;13(1):824. https://doi.org/10.1038/s41467-022-28329-1

37. Selariu A, Cheng T, Tang Q, et al. ORF7 of varicella-zoster virus is a neurotropic factor. J Virol. 2012;86(16):8614–24. https://doi.org/10.1128/JVI.00128-12

38. Ulaszewska M, Merelie S, Sebastian S, Lambe T. Preclinical immunogenicity of an adenovirus-vectored vaccine for herpes zoster. Hum Vaccin Immunother. 2023;19(1):2175558. https://doi.org/10.1080/21645515.2023.2175558

39. Petherbridge L, Davis C, Robinson A, et al. Pre-clinical development of an adenovirus vector based RSV and shingles vaccine candidate. Vaccines (Basel). 2023;11(11):1679. https://doi.org/10.3390/vaccines11111679

40. Zheng Y, Huang L, Ding H, et al. Immunogenicity in mice immunized with recombinant adenoviruses expressing varicella-zoster virus envelope glycoprotein E. Viruses. 2023;15(12):2288. https://doi.org/10.3390/v15122288

41. Bhattacharya A, Jan L, Burlak O, et al. Potent and long-lasting humoral and cellular immunity against varicella zoster virus induced by mRNA-LNP vaccine. NPJ Vaccines. 2024;9(1):72. https://doi.org/10.1038/s41541-024-00865-5

42. Cao H, Wang Y, Luan N, Lin K, Liu C. Effects of varicella-zoster virus glycoprotein E carboxyl-terminal mutation on mRNA vaccine efficacy. Vaccines (Basel). 2021;9(12);1440. https://doi.org/10.3390/vaccines9121440

43. Bao L, Wei G, Gan H, et al. Immunogenicity of varicella zoster virus glycoprotein E DNA vaccine. Exp Ther Med. 2016;11(5):1788–94. https://doi.org/10.3892/etm.2016.3086

44. Liu J, Lin J, Cai L, et al. Immunogenicity of varicella zoster virus DNA vaccines encoding glycoprotein E and immediate early protein 63 in mice. Viruses. 2022;14(6):1214. https://doi.org/10.3390/v14061214

45. Zverev VV, Nagieva FG, Barkova EP, Osokina OV. Strain “vFiraVax” for producing an attenuated alive culture vaccine for preventing varicella. Patent of the Russian Federation No. 2693440; 2019 (In Russ.). EDN: JWECLO

46. Zverev VV, Nagieva FG, Barkova EP, et al. Viral strain for obtaining attenuated live culture vaccine for prevention and treatment of herpes zoster for adult population. Patent of the Russian Federation No. 2750818; 2020 (In Russ.). EDN: ACINJQ


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Zotova A.V., Svitich O.A. Varicella and Herpes zoster vaccines: from live attenuated vaccines to genetically engineered products. Biological Products. Prevention, Diagnosis, Treatment. (In Russ.) https://doi.org/10.30895/2221-996X-2025-645

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ISSN 2221-996X (Print)
ISSN 2619-1156 (Online)