VZV T Cell-Mediated Immunity

Weinberg, Adriana; Levin, Myron J.

doi:10.1007/82_2010_31

Cited by 148 publications

(154 citation statements)

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“…In some studies, CD8 ϩ T cells were either undetected or present at low frequencies following VZV infection or vaccination in healthy subjects, in contrast to the more abundantly and frequently detected VZV-specific CD4 ϩ T cells (1). A VZV glycoprotein E vaccine induced VZV-specific CD4…”

Section: Discussionmentioning

confidence: 99%

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High-Level Cellular and Humoral Immune Responses in Guinea Pigs Immunized Intradermally with a Heat-Inactivated Varicella-Zoster Virus Vaccine

Sarkadi

Jankovics

Fodor

et al. 2015

Clin. Vaccine Immunol.

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V aricella-zoster virus (VZV) causes varicella by primary infection and herpes zoster by reactivation of the latent virus in the sensory ganglia of infected individuals. After primary infection, the immune response comprises VZV-specific antibody and T cell-mediated immunity (CMI), which are important for recovery from varicella. T cell responses are necessary to control latent VZV in the sensory ganglia. A lack or a declining level of CMI to VZV has been associated with a higher risk of development of herpes zoster (1).A varicella vaccine consisting of live, attenuated strain OKA (vOKA) has been developed in Japan and licensed for mass vaccination in Japan, South Korea, the United States, and several European countries or recommended for only selected groups of the population in other countries (2, 3). To prevent herpes zoster, a zoster vaccine containing 14 times as many PFU of vOKA than the varicella vaccine was developed and licensed for the vaccination of immunocompetent subjects older than 60 years in the United States in 2006 (4). Varicella and zoster vaccines are administered by the subcutaneous (s.c.) route. However, vaccination of immunocompromised individuals with live VZV vaccines can be problematic and different strategies for safe immunization need to be explored (5).Several clinical studies have indicated that the use of a heatinactivated VZV vaccine is an alternative mode of immunization of immunocompromised individuals. Triple vaccination of bone marrow transplant patients with a heat-inactivated varicella vaccine administered s.c. decreased the severity of herpes zoster (6) and four s.c. doses of a heat-inactivated zoster vaccine proved safe and immunogenic in patients with tumor malignancy, HIV-infected individuals, or hematopoietic stem cell transplant recipients (7). When healthy elderly subjects were immunized s.c. with a single dose of either live or heat-inactivated varicella vaccine, there were no differences in antibody responses or IFN-␥ production by peripheral blood mononuclear cells (8). These data indicated that a heat-inactivated VZV vaccine might be useful in preventing herpes zoster. However, protection against herpes zoster following immunization with either a live or heat-inactivated vaccine is not optimal and a more potent antigenic stimulus is needed to improve the efficacy of the vaccine in high-risk patients (9).The skin is a highly immunogenic organ (10). Noninvasive, needle-free liquid jet injection of liquid or powder into the skin has been used in clinical trials for immunization against viral infections (11-13). The barrier structure and thickness of the stratum corneum, the outermost layer of the skin, are similar in guinea pigs and humans (18.6 and 18.2 m, respectively) (14), and thus, the i.d. route of immunization and the effectiveness of a potential i.d. delivery device for humans can be tested in guinea pigs. Moreover, the parental OKA strain is attenuated in human

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Section: Discussionmentioning

confidence: 99%

“…T cell responses are necessary to control latent VZV in the sensory ganglia. A lack or a declining level of CMI to VZV has been associated with a higher risk of development of herpes zoster (1).…”

mentioning

confidence: 99%

High-Level Cellular and Humoral Immune Responses in Guinea Pigs Immunized Intradermally with a Heat-Inactivated Varicella-Zoster Virus Vaccine

Sarkadi

Jankovics

Fodor

et al. 2015

Clin. Vaccine Immunol.

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“…Similar to CMV, analysis of the cellular responses to VZV and HSV has primarily focused upon lytic cycle antigens. These studies have also demonstrated diversity in the antigenic targets of HSV and VZV-specific T cells, with immunodominant responses generated in response to both structural antigens, including tegument proteins and surface glycoprotein and nonstructural antigens (68,69). Phenotypically, HSV and VZV-specific T cells in asymptomatically infected donors more closely resemble EBV-specific T cell populations, although their frequency is generally an order of magnitude lower (70)(71)(72).…”

Section: T Cell Immunity To Ebv and Other Human Herpesvirusesmentioning

confidence: 97%

Immune Regulation of Human Herpesviruses and Its Implications for Human Transplantation

Smith

Khanna

2013

American Journal of Transplantation

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Human herpesviruses including cytomegalovirus, Epstein-Barr virus, HHV6, HHV7, HHV8, Herpes simplex virus (HSV)-1 and HSV-2 and varicella zoster virus (VZV) have developed an intricate relationship with the human immune system. This is characterized by the interplay between viral immune evasion mechanisms that promote the establishment of a lifelong persistent infection and the induction of a broad humoral and cellular immune response, which prevents the establishment of viral disease. Understanding the immune parameters that control herpesvirus infection, and the strategies the viruses use to evade immune recognition, has been critical in understanding why immunological dysfunction in transplant patients can lead to disease, and in the development of immunological strategies to prevent and control herpesvirus associated diseases.

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“…23 Amongst those, glycoprotein E (gE), IE62, and IE63 were defined as being immunodominant. [24][25][26][27][28] The screening approaches that led to these findings mainly used memory T-cell populations which were expanded from PBMC of latently infected healthy individuals by antigen-specific stimulation over a culture period of several days to weeks. However, prolonged culturing may favor the proliferation of certain T-cell specificities over others and, consequently, the observed profile may not necessarily reflect the hierarchy of immunogenicity of different VZV antigens in vivo.…”

Section: Varicella-zoster Virus Glycoproteins B and E Are Major Targementioning

confidence: 99%

Varicella-zoster virus glycoproteins B and E are major targets of CD4+ and CD8+ T cells reconstituting during zoster after allogeneic transplantation

Kleemann

Distler²,

Wagner³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundAfter allogeneic hematopoietic stem-cell transplantation patients are at increased risk for herpes zoster as long as varicella-zoster virus specific T-cell reconstitution is impaired. This study aimed to identify immunodominant varicella-zoster virus antigens that drive recovery of virusspecific T cells after transplantation. Design and MethodsAntigens were purified from a varicella-zoster virus infected cell lysate by high-performance liquid chromatography and were identified by quantitative mass spectrometric analysis. To approximate in vivo immunogenicity for memory T cells, antigen preparations were consistently screened with ex vivo PBMC of varicella-zoster virus immune healthy individuals in sensitive interferon-γ ELISpot assays. Candidate virus antigens identified by the approach were genetically expressed in PBMC using electroporation of in vitro transcribed RNA encoding full-length proteins and were then analyzed for recognition by CD4 + and CD8 + memory T cells. ResultsVaricella-zoster virus encoded glycoproteins B and E, and immediate early protein 62 were identified in immunoreactive lysate material. Predominant CD4 + T-cell reactivity to these proteins was observed in healthy virus carriers. Furthermore, longitudinal screening in allogeneic stem-cell transplantation patients showed strong expansions of memory T cells recognizing glycoproteins B and E after onset of herpes zoster, while immediate early protein 62 reactivity remained moderate. Reactivity to viral glycoproteins boosted by acute zoster was mediated by both CD4 + and CD8 + T cells. ConclusionsOur data demonstrate that glycoproteins B and E are major targets of varicella-zoster virus specific CD4 + and CD8 + T-cell reconstitution occurring during herpes zoster after allogeneic stemcell transplantation. Varicella-zoster virus glycoproteins B and E might form the basis for novel non-hazardous zoster subunit vaccines suitable for immunocompromised transplant patients.

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VZV T Cell-Mediated Immunity

Cited by 148 publications

References 75 publications

High-Level Cellular and Humoral Immune Responses in Guinea Pigs Immunized Intradermally with a Heat-Inactivated Varicella-Zoster Virus Vaccine

High-Level Cellular and Humoral Immune Responses in Guinea Pigs Immunized Intradermally with a Heat-Inactivated Varicella-Zoster Virus Vaccine

Immune Regulation of Human Herpesviruses and Its Implications for Human Transplantation

Varicella-zoster virus glycoproteins B and E are major targets of CD4+ and CD8+ T cells reconstituting during zoster after allogeneic transplantation

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