Varicella zoster virus quantitation in blood from symptomatic and asymptomatic individuals

Toi, Cheryl; Lay, Meav-Lang J; Lucas, Robyn; Chew, Choo Beng; Taylor, Janette; Ponsonby, Anne–Louise; Dwyer, Dominic E.

doi:10.1002/jmv.23605

Cited by 8 publications

(4 citation statements)

References 32 publications

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“…Thus, ZV might be valuable as a surrogate of VZV reactivation to determine the differences in CMI responses between older and young adults. This may provide important information about the nature of immune protection against HZ and why older adults are more likely to develop HZ, including more severe HZ, after VZV reactivation than young adults (13, 14). …”

Section: Introductionmentioning

confidence: 99%

Varicella-Zoster Virus–Specific Cellular Immune Responses to the Live Attenuated Zoster Vaccine in Young and Older Adults

Weinberg

Canniff

Rouphael

et al. 2017

The Journal of Immunology

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The incidence and severity of herpes zoster (HZ) increases with age. The live attenuated zoster vaccine (ZV) generates immune responses similar to HZ. We compared the immune responses to ZV in young and older to adults to increase our understanding of the immune characteristics that may contribute to the increased susceptibility to HZ in older adults. Young (25–40 years; N=25) and older (60–80 years; N=33) adults had similar magnitude memory responses to varicella-zoster virus (VZV) ex-vivo restimulation measured by responder cell-frequency (RCF) and flow cytometry, but the responses were delayed in older compared with young adults. Only young adults had an increase in dual-function VZV-specific CD4+ and CD8+ T cell effectors defined by co-expression of IFNγ, IL2 and CD107a after vaccination. In contrast, older adults showed marginal increases in VZV-specific CD8+CD57+ senescent T cells after vaccination, which were already higher than those of young adults before vaccination. An increase in VZV-stimulated CD4+CD69+CD57+PD1+ and CD8+CD69+CD57+PD1+ T cells from baseline to post-vaccination was associated with concurrent decreased VZV-memory and CD8+ effector responses, respectively, in older adults. Blocking the PD1 pathway during ex-vivo VZV restimulation increased the CD4+ and CD8+ proliferation, but not the effector cytokine production, which modestly increased with TIM-3 blockade. We conclude that high proportions of senescent and exhausted VZV-specific T cells in the older adults contribute to their poor effector responses to a VZV challenge. This may underlie their inability to contain VZV reactivation and prevent the development of HZ.

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Section: Introductionmentioning

confidence: 99%

Varicella-Zoster Virus–Specific Cellular Immune Responses to the Live Attenuated Zoster Vaccine in Young and Older Adults

Weinberg

Canniff

Rouphael

et al. 2017

The Journal of Immunology

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“…According to Toi et al, clinical and asymptomatic reactivation of VZV with viremia may occur. [11] Varicella is a well-known contagious disease that can affect both immune compromised and immune competent adults. An apparently healthy adult patient can present with a fulminant hepatitis evolving in multiorgan failure, associated with an atypical papuloerythemateous cutaneous rash without fever.…”

Section: Discussionmentioning

confidence: 99%

Maternal Death due to Viral Sepsis

Amararatne¹,

Vidanapathirana

2019

Medico-Legal J SL

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Sepsis accounts for approximately 10% of all maternal deaths and in pregnancy, as a result of cell-mediated immunity is altered and prone for infection. Varicella zoster virus (VZV) commonly causes chickenpox in children and herpes zoster in adults. In this case, viral sepsis probably due to VZV has caused a death of an apparently immune-competent young mother. A 19-year-old unmarried sex worker with Grave's disease presented in her second trimester with ankle oedema and shortness of breath. She was hypertensive and anaemic and was treated for secondary hypertension due to thyrotoxicosis. Later, she developed fever, oliguria and heart failure. She was treated in intensive care unit with hyperthyroid crisis induced by sepsis due to pneumonia. She developed high fever, intra-uterine death, hepato-renal failure, disseminated intravascular coagulation (DIC) and died on day fourteen. At autopsy, dermotomal vesicular skin lesions and vulval viral warts were seen. The internal organs showed sepsis. Blood for HIV was negative. Histopathology revealed viral pneumonia, myocarditis and DIC. Cause of death was given as sepsis due to viral pneumonia probably following VZV. The clinical diagnosis was septicaemia, due to pneumonia, but herpes zoster infection was not diagnosed. VZV infection can be life threatening even in immune-competent adults. The diagnosis of multi-organ failure from VZV should always be clinically suspected in the presence of atypical skin lesions and a temporarily immune-compromised state such as pregnancy.

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“…As the antibodies that were detected after Zostavax vaccination had a high degree of somatic hypermutations (median, 20; range, 7 to 34), it is unclear whether these mutations were a result of primary infection, exogenous exposure to varicella, or subclinical reactivation over time. There have been some reports that VZV DNA can be detected in the blood of some healthy individuals (61). These data suggest that subclinical reactivation and subsequent boosting of the immune response may occur as people age.…”

Section: Figmentioning

confidence: 91%

Breadth and Functionality of Varicella-Zoster Virus Glycoprotein-Specific Antibodies Identified after Zostavax Vaccination in Humans

Sullivan

Reuter-Monslow

Sei

et al. 2018

J Virol

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Herpes zoster (HZ) (shingles) is the clinical manifestation of varicella-zoster virus (VZV) reactivation. HZ typically develops as people age, due to decreased cell-mediated immunity. However, the importance of antibodies for immunity against HZ prevention remains to be understood. The goal of this study was to examine the breadth and functionality of VZV-specific antibodies after vaccination with a live attenuated HZ vaccine (Zostavax). Direct enumeration of VZV-specific antibody-secreting cells (ASCs) via enzyme-linked immunosorbent spot assay (ELISPOT assay) showed that Zostavax can induce both IgG and IgA ASCs 7 days after vaccination but not IgM ASCs. The VZV-specific ASCs range from 33 to 55% of the total IgG ASCs. Twenty-five human VZV-specific monoclonal antibodies (MAbs) were cloned and characterized from single-cell-sorted ASCs of five subjects (>60 years old) who received Zostavax. These MAbs had an average of ∼20 somatic hypermutations per VH gene, similar to those seen after seasonal influenza vaccination. Fifteen of the 25 MAbs were gE specific, whereas the remaining MAbs were gB, gH, or gI specific. The most potent neutralizing antibodies were gH specific and were also able to inhibit cell-to-cell spread of the virus Most gE-specific MAbs were able to neutralize VZV, but they required the presence of complement and were unable to block cell-to-cell spread. These data indicate that Zostavax induces a memory B cell recall response characterized by anti-gE> anti-gI > anti-gB > anti-gH antibodies. While antibodies to gH could be involved in limiting the spread of VZV upon reactivation, the contribution of anti-gE antibodies toward protective immunity after Zostavax needs further evaluation. Varicella-zoster virus (VZV) is the causative agent of chickenpox and shingles. Following infection with VZV, the virus becomes latent and resides in nerve cells. Age-related declines in immunity/immunosuppression can result in reactivation of this latent virus, causing shingles. It has been shown that waning T cell immunity correlates with an increased incidence of VZV reactivation. Interestingly, serum with high levels of VZV-specific antibodies (VariZIG; IV immunoglobulin) has been administered to high-risk populations, e.g., immunocompromised children, newborns, and pregnant women, after exposure to VZV and has shown some protection against chickenpox. However, the relative contribution of antibodies against individual surface glycoproteins toward protection from shingles in elderly/immunocompromised individuals has not been established. Here, we examined the breadth and functionality of VZV-specific antibodies after vaccination with the live attenuated VZV vaccine Zostavax in humans. This study will add to our understanding of the role of antibodies in protection against shingles.

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Varicella zoster virus quantitation in blood from symptomatic and asymptomatic individuals

Cited by 8 publications

References 32 publications

Varicella-Zoster Virus–Specific Cellular Immune Responses to the Live Attenuated Zoster Vaccine in Young and Older Adults

Varicella-Zoster Virus–Specific Cellular Immune Responses to the Live Attenuated Zoster Vaccine in Young and Older Adults

Maternal Death due to Viral Sepsis

Breadth and Functionality of Varicella-Zoster Virus Glycoprotein-Specific Antibodies Identified after Zostavax Vaccination in Humans

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