All Issue

2021 Vol.51, Issue 3 Preview Page

Review Article

Immune Responses to Varicella Zoster Virus and Effective Vaccines
Su Jeen Lee12
Hun Kim2
Kee-Jong Hong3
Jae-Hwan Nam1*
1Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon 14662, Republic of Korea
2Department of R&D, SK bioscience, Pangyo-ro 332, Bundang-gu 13494, Republic of Korea
3UIC Foundation, Konkuk University, Neungdong-ro 120, Gwangjin-gu, Seoul 05029, Republic of Korea
*jhnam@catholic.ac.kr
30 September 2021. pp. 103-111
PDF XML Citation
Abstract

Varicella zoster virus (VZV) causes two distinct diseases, varicella (chickenpox) during primary infection, and herpes zoster (shingles) resulting from reactivation. The purpose of this review is to summarize the present understanding of VZV and the associated immune response, as well as to discuss available vaccines. VZV infection induces both innate and adaptive immune responses, especially an antigen-specific adaptive immune response, which activates humoral immunity and cell-mediated immunity (CMI). Reactivation of VZV can occur when the CMI of latent VZV is reduced, leading to herpes zoster. After VZV infection, natural killer (NK) cells modulate antigen presentation and the production of IFN-γ, an important activator of macrophages. IFN-γ is produced by NK cells and CD4 Th1/CD8 cytotoxic T lymphocytes. The T cell-mediated immune response is an important factor influencing VZV reactivation and herpes zoster, with herpes zoster being associated with reduced levels of VZV-specific T cells. Since the VZV-specific T cell population gradually declines with age, herpes zoster particularly affects the elderly. There are two types of zoster vaccines: live-attenuated and recombinant subunit. However, recombinant vaccines generally have poor immunogenicity when administered alone and require an adjuvant. Therefore, effective adjuvants are needed that especially promote cell-mediated immune responses. Various adjuvants have been developed, many of which enhance T cell immunity more than antibody-based humoral immunity. The information presented in this review may serve as a reference for future VZV immunology studies.

Keywords
Cell-mediated immunity
Herpes zoster
Humoral immunity
Varicella zoster virus
Adjuvants
VZV vaccine
References
1

Wang L, Verschuuren EAM, van Leer-Buter CC, Bakker SJL, de Joode AAE, Westra J, et al. Herpes zoster and immunogenicity and safety of zoster vaccines in transplant patients: A narrative review of the literature. Front Immunol 2018;9:1632.

10.3389/fimmu.2018.0163230079064PMC6062765
2

Levin MJ. Immune senescence and vaccines to prevent herpes zoster in older persons. Curr Opin Immunol 2012;24: 494-500.

10.1016/j.coi.2012.06.00222857823
3

van der Heiden M, de Rond LGH, van Zelm MC, Berbers GAM, Boots AMH, Buisman AM. Age-Dependent Pre-Vaccination Immunity Affects the Immunogenicity of Varicella Zoster Vaccination in Middle-aged Adults. Front Immunol 2018;9:46.

10.3389/fimmu.2018.0004629410671PMC5787056
4

Papaloukas O, Giannouli G, Papaevangelou V. Successes and challenges in varicella vaccine. Ther Adv Vaccines 2014;2:39-55.

10.1177/205101361351562124757524PMC3991154
5

Zerboni L, Sen N, Oliver SL, Arvin AM. Molecular mechanisms of varicella zoster virus pathogenesis. Nat Rev Microbiol 2014;12:197-210.

10.1038/nrmicro321524509782PMC4066823
6

Peters GA, Tyler SD, Grose C, Severini A, Gray MJ, Upton C, et al. A Full-Genome Phylogenetic Analysis of Varicella-Zoster Virus Reveals a Novel Origin of Replication-Based Genotyping Scheme and Evidence of Recombination between Major Circulating Clades. J Virol 2006;80:9850-60.

10.1128/JVI.00715-0616973589PMC1617253
7

Al-Anazi KA, Al-Anazi WK, Al-Jasser AM. The beneficial effects of varicella zoster virus. J Hematol Clin Res 2019;3:16-49.

10.29328/journal.jhcr.1001010
8

Arvin AM. Varicella-Zoster Virus. Clin Microbiol Rev 1996;9:361-81.

10.1128/CMR.9.3.3618809466PMC172899
9

Vafai A. Varicella-Zoster Virus Subunit Vaccine. The Open Vaccine Journal 2009;2:17-27.

10.2174/1875035400902010017
10

Olson JK, Santos RA, Grose C. Varicella-zoster virus glycoprotein gE: endocytosis and trafficking of the Fc receptor. J Infect Dis 1998;178:S2-6.

10.1086/5142559852964
11

Oliver SL, Yang E, Arvin AM. Varicella-Zoster virus glycoproteins: Entry, Replication, and Pathogenesis. Curr Clin Microbiol Rep 2016;3:204-15.

10.1007/s40588-016-0044-428367398PMC5373811
12

Warren-Gash C, Forbes H, Breuer J. Varicella and herpes zoster vaccine development: lessons learned. Expert Rev Vaccines 2017;16:2291-201.

10.1080/14760584.2017.139484329047317PMC5942150
13

Pasquale AD, Preiss S, Silva FTD, Garçon N. Vaccine Adjuvants: from 1920 to 2015 and Beyond. Vaccines 2015;16:320-43.

10.3390/vaccines302032026343190PMC4494348
14

Abendroth A, Lin I, Slobedman B, Ploegh H, Arvin AM. Varicella-zoster virus retains major histocompatibility complex class I proteins in the golgi compartment of infected cells. J Virol 2001;75:4878-88.

10.1128/JVI.75.10.4878-4888.200111312359PMC114242
15

Gershon AA, Breuer J, Cohen JI, Cohrs RJ, Gershon MD, Gilden D, et al. Varicella-zoster virus infection. Nat Rev Dis Primers 2015;1:15016.

10.1038/nrdp.2015.1627188665PMC5381807
16

Abendroth A, Kinchington PR, Slobedman B. Varicella zoser virus immune evasion strategies. Curr Top Microbiol Immunol 2010;324:155-71.

10.1007/82_2010_4120563710PMC3936337
17

Arvin AM. Humoral and Cellular Immunity to Varicella-Zoster Virus: An Overview. J Infect Dis 2008;197:S58-60.

10.1086/52212318419410
18

Gerade C, Campbell TM, Kennedy JJ, McSharry BP, Steain M, Slobedman B, et al. Manipulation of the innate immune response by varicella zoster virus. Front Immunol 2020;11:1.

10.3389/fimmu.2020.0000132038653PMC6992605
19

Sironi M, Peri AM, Cagliani R, Forni D, Riva S, Biasin M, et al. TLR3 Mutations in Adult Patients With Herpes Simplex Virus and Varicella-Zoster Virus Encephalitis. J Infect Dis 2017;215:1430-4.

10.1093/infdis/jix16628368532
20

Laing KJ, Ouwendijk WJD, Koelle DM, Verjans GMGM. Immunobiology of Varicella-Zoster virus infection. J infect Dis 2018;218:S68-74.

10.1093/infdis/jiy40330247598PMC6151075
21

Schönrich G, Raftery MJ. Dendritic cells as Achilles' heel and Trojan horse during varicella zoster virus infection. Front Microbiol 2015;6:417.

10.3389/fmicb.2015.0041726005438PMC4424880
22

Sadaoka K, Okamoto S, Gomi Y, Ishikawa T, Yoshikawa T, Asano Y, et al. Measurement of varicella-zoster virus (VZV)-specific cell-mediated immunity: comparison between VZV skin test and interferon-gamma enzyme-linked immunospot assay. J Infect Dis 2008;198:1327-33.

10.1086/59221918774884
23

Steain M, Sutherland JP, Rodriguez M, Cunningham AL, Slobedman B, Abendroth A. Analysis of T cell responses during active varicella-zoster virus reactivation in human ganglia. J Virol 2014;88:2704-16.

10.1128/JVI.03445-1324352459PMC3958057
24

Weinberg A, Canniff J, Rouphael N, Mehta A, Mulligan M, Whitaker JA, et al. Varicella-Zoster Virus-specific cellular immune response to the live attenuated zoster vaccine in young and older adults. J Immunol 2017;199:604-12.

10.4049/jimmunol.170029028607114PMC5505810
25

Sei JJ, Cox KS, Dubey SA, Antonello JM, Krah DL, Casimiro DR, et al. Effector and central memory poly-functional CD4(+) and CD8(+) T cells are boosted upon ZOSTAVAX(®) vaccination. Front Immunol 2015;6:553.

10.3389/fimmu.2015.0055326579128PMC4629102
26

Arvin A, Abendroth A. VZV: immunobiology and host response. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge University Press; 2007. chapter 39.

27

Weinberg A, Levin MJ. VZV T-cell mediated immunity. Curr Top Microbiol Immunol 2010;342:341-57.

10.1007/82_2010_3120473790
28

Yu HR, Chen RF, Hong KC, Bong CN, Lee WI, Kuo HC, et al. IL-12 independent Th1 polarization in human mononuclear cells infected with varicella-zoster virus. Eur J Immunol 2005;35:3664-72.

10.1002/eji.20052625816285008
29

Torigo S, Ihara T, Kamiya H. IL-12, IFN-r, and TNF-α released from mononuclear cells inhibit the spread of varicella- zoster virus at an early stage of varicella. Microbiol Immunol 2000;44:1027-31.

10.1111/j.1348-0421.2000.tb02599.x11220676
30

Zajkowska A, Garkowski A, Świerzbińska R, Kułakowska A, Król ME, Ptaszyńska-Sarosiek I, et al. Evaluation of chosen cytokine levels among patients with herpes zoster as ability to provide immune response. PLoS One 2016;11:e0150301.

10.1371/journal.pone.015030126934574PMC4775057
31

Jenkins DE, Redman RL, Lam EM, Liu C, Lin I, Arvin AM. Interleukin (IL)-10, IL-12, and interferon-gamma production in primary and memory immune responses to varicella-zoster virus. J infect Dis 1998;178:940-8.

10.1086/5157029806019
32

Frey CR, Sharp MA, Min AS, Schmid DS, Loparev V, Arvin AM. Identification of CD8+ T cell epitopes in the immediate early 62 protein (IE62) of varicella-zoster virus, and evaluation of frequency of CD8+ T cell response to IE62, by use of IE62 peptides after varicella vaccination. J infect Dis 2003;188:40-52.

10.1086/37582812825169
33

Ogunjimi B, Smits E, Heynderickx S, Van den Bergh J, Bilcke J, Jansens H, et al. Influence of Frequent Infectious Exposures on General and Varicella-Zoster Virus-Specific Immune Responses in Pediatricians. Clin Vaccine Immunol 2014;21:417-26.

10.1128/CVI.00818-1324429070PMC3957663
34

Levin MJ, Oxman MN, Zhang JH, Johnson GR, Stanley H, Hayward AR, et al. Varicella-Zoster Virus-Specific Immune Responses in Elderly Recipients of a Herpes Zoster Vaccine. J infect Dis 2008;197:825-35.

10.1086/52869618419349PMC4014857
35

Weinberg A, Pang L, Johnson MJ, Caldas Y, Cho A, Tovar-Salazar A, et al. The Effect of Age on the Immunogenicity of the Live Attenuated Zoster Vaccine Is Predicted by Baseline Regulatory T Cells and Varicella-Zoster Virus-Specific T Cell Immunity. J Virol 2019;93:e00305-19.

10.1128/JVI.00305-19
36

Gabutti G, Bolognesi N, Sandri F, Florescu C, Stefanati A. Varicella zoster virus vaccines: an update. ImmunoTargets Ther 2019;8:15-28.

10.2147/ITT.S17638331497569PMC6689529
37

Levin MJ, Weinberg A. Immune responses to zoster vaccines. Hum Vaccin Immunother 2019;15:772-7.

10.1080/21645515.2018.156091830676834PMC6605864
38

Sadaoka T, Mori Y. Vaccine Development for Varicella-Zoster Virus. Adv Exp Med Biol 2018;1045:123-42.

10.1007/978-981-10-7230-7_729896666
39

Cunningham AL. The herpes zoster subunit vaccine. Expert Opin Biol Ther 2016;16:265-71.

10.1517/14712598.2016.113448126865048
40

Dendouga N, Fochesato M, Lockman L, Mossman S, Giannini SL. Cell-mediated immune responses to a varicella-zoster virus glycoprotein E vaccine using both a TLR agonist and QS21 in mice. Vaccine 2012;30:3126-35.

10.1016/j.vaccine.2012.01.08822326899
41

Levin MJ, Weinberg A. Adjuvanted recombinant glycoprotein E herpes zoster vaccine. Clin Infect Dis 2020;70:1509-15.

10.1093/cid/ciz77031618437
42

Gershon AA. Tale of two vaccines: differences in response to herpes zoster vaccines. J Clin Invest 2018;128:4245-7.

10.1172/JCI12321730179221PMC6159952
43

Brosio F, Masetti G, Matteo G, Stefanati A, Gabutti G. A novel nonlive, adjuvanted herpes zoster subunit vaccine: a report on the emerging clinical data and safety profile. Infect Drug Resist 2018;11:1401-11.

10.2147/IDR.S14830330233219PMC6130298
44

Weinberg A, Kroehl ME, Johnson MJ, Hammes A, Reinhold D, Lang N, et al. Comparative Immune Responses to Licensed Herpes Zoster Vaccines. J Infect Dis 2018;218:S81-7.

10.1093/infdis/jiy38330247596
45

Mohan T, Verma P, Rao DN. Novel adjuvants & delivery vehicles for vaccines development: a road ahead. Indian J Med Res 2013;138:779-95.

46

O'Hagan DT. Recent developments in vaccine delivery systems. Curr Drug Targets Infect Disord 2001;1:273-86.

10.2174/156800501460600812455401
47

Bonam SR, Partidos CD, Halmuthur SKM, Muller S. An Overview of Novel Adjuvants Designed for Improving Vaccine Efficacy. Trends Pharmacol Sci 2017;38:771-93.

10.1016/j.tips.2017.06.00228668223
48

Vandepapelière P, Horsmans Y, Moris P, Van Mechelen M, Janssens M, Koutsoukos M, et al. Vaccine adjuvant systems containing monophosphoryl lipid A and QS21 induce strong and persistent humoral and T cell responses against hepatitis B surface antigen in healthy adult volunteers. Vaccine 2008;26:1375-86.

10.1016/j.vaccine.2007.12.03818272264
49

Leroux-Roels G. Unmet needs in modern vaccinology: adjuvants to improve the immune response. Vaccine 2010;28:C25-36.

10.1016/j.vaccine.2010.07.02120713254
50

Harini PA, Kumar HGA, Kumar GP, Neeta S. An Overview of Immunologic Adjuvants - A Review. J Vaccines Vaccin 2013;4:1-4.

51

Vasou A, Sultanoglu N, Goodbourn S, Randall RE, Kostrikis LG. Targeting Pattern Recognition Receptors (PRR) for Vaccine Adjuvantation: From Synthetic PRR Agonists to the Potential of Defective Interfering Particles of Viruses. Viruses 2017;9:186.

10.3390/v907018628703784PMC5537678
52

Arnold N, Messaoudi I. Herpes zoster and the search for an effective vaccine. Clin Exp Immunol 2017;187:82-92.

10.1111/cei.1280927164323PMC5167054
Information
  • Publisher :The Korean Society for Microbiology
  • Publisher(Ko) :대한미생물학회
  • Journal Title :JOURNAL OF BACTERIOLOGY AND VIROLOGY
  • Volume : 51
  • No :3
  • Pages :103-111
  • Received Date :2021. 08. 23
  • Revised Date :2021. 09. 17
  • Accepted Date : 2021. 09. 23
  • DOI :https://doi.org/10.4167/jbv.2021.51.3.103
Journal Informaiton JOURNAL OF BACTERIOLOGY AND VIROLOGY JOURNAL OF BACTERIOLOGY AND VIROLOGY
  • NRF
  • 임플란트학회 전용 배너
  • KOFST
  • crossref crossmark
  • crossref cited-by
  • crossref funder-registry
  • crosscheck
  • orcid
  • open access
  • ccl
Journal Informaiton Journal Informaiton - close