Influence of Frequent Infectious Exposures on General and Varicella-Zoster Virus-Specific Immune Responses in Pediatricians

Ogunjimi, Benson; Smits, Evelien; Heynderickx, Steven; Bergh, Johan van den; Bilcke, Joke; Jansens, Hilde; Malfait, Ronald; Ramet, José; Maecker, Holden T.; Cools, Nathalie; Beutels, Philippe; Damme, Pierre Van

doi:10.1128/cvi.00818-13

Cited by 28 publications

(25 citation statements)

References 71 publications

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“…Our findings were consistent with the finding that paediatricians have similar VZV-specific antibody titres as control adults 3 and that no systematic signs of the boosting of VZV-specific antibodies were observed in re-exposed parents 1,2,4 .…”

Section: Discussionsupporting

confidence: 92%

Multidisciplinary study of the secondary immune response in grandparents re-exposed to chickenpox

Ogunjimi

Bergh

Meysman

et al. 2017

Sci Rep

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Re-exposure to chickenpox may boost varicella-zoster virus (VZV) immunity in the elderly. This secondary immune response is hypothesized to confer protection against herpes zoster. We longitudinally sampled 36 adults over the course of one year after re-exposure to chickenpox. The resulting 183 samples and those of 14 controls were assessed for VZV-specific T-cell immunity and antibody titres. The percentages of VZV-specific CD4+ IL-2-producing T-cells were increased in re-exposed grandparents compared to control participants up to 9 months after re-exposure. Using a longitudinal mixture modelling approach, we found that 25% and 17% of re-exposed grandparents showed a boosting of VZV-specific CD4+ IL-2-producing T-cells and VZV-specific antibodies, respectively. The antibody boosting occurred exclusively in cytomegalovirus (CMV) IgG-positive participants. CMV IgG-positive participants also had higher VZV IE62-specific CD4+ IFN-γ-producing T-cell percentages and VZV-specific antibody titres. The protective effect of re-exposure to chickenpox is likely limited, as boosting only occurred in 17–25% of the VZV re-exposed grandparents and for less than one year.

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Section: Discussionsupporting

confidence: 92%

Multidisciplinary study of the secondary immune response in grandparents re-exposed to chickenpox

Ogunjimi

Bergh

Meysman

et al. 2017

Sci Rep

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“…Rapid and/or polyfunctional effector responses may contribute to control of viral replication and prevent HZ. This is in agreement with the immune mechanism that controls other herpesviral infections (27, 28) and with previous reports showing that adults with recent and/or frequent exposures to VZV, who did not develop symptomatic VZV infection, had robust VZV-specific CD8+ and CD4+ T cell responses detected by ex vivo restimulation (29–31). The important role of CD8+ T cells in the control of VZV replication could also be inferred from the accumulation of this T cell subset in the ganglia of individuals with HZ, where VZV is actively replicating (32).…”

Section: Discussionsupporting

confidence: 92%

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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“…Additionally, as recently shown, CMV-seronegative individuals can have CMVresponsive T-cells thereby suggesting a former encounter with CMV, and this might also have affected our analyses. 23,24 Finally, our study is the first to show an association between CMV infection and HZ, further causal relations should be studied in other studies.…”

Section: Discussionmentioning

confidence: 66%

Cytomegalovirus seropositivity is associated with herpes zoster

Ogunjimi

Hens

Pebody

et al. 2015

Human Vaccines & Immunotherapeutics

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Herpes zoster (HZ) is caused by VZV reactivation that is facilitated by a declined immunity against varicella-zoster virus (VZV), but also occurs in immunocompetent individuals. Cytomegalovirus (CMV) infection is associated with immunosenescence meaning that VZV-specific T-cells could be less responsive. This study aimed to determine whether CMV infection could be a risk factor for the development of HZ. CMV IgG serostatus was determined in stored serum samples from previously prospectively recruited ambulatory adult HZ patients in the UK (N D 223) in order to compare the results with those from UK population samples (N D 1545) by means of a logistic regression (controlling for age and gender). Furthermore, we compared the UK population CMV seroprevalence with those from population samples from other countries (from Belgium (N1 D 1741, N2 D 576), USA (N D 5572) and Australia (N D 2080)). Furthermore, CMV IgG titers could be compared between UK HZ patients and Belgium N2 population samples because the same experimental set-up for analysis was used. We found UK ambulatory HZ patients to have a higher CMV seroprevalence than UK population samples (OR 1.56 [1.11 2.19]). CMV IgG seropositivity was a significant risk factor for HZ in the UK (OR 3.06 [1.32 7.04]. Furthermore, high CMV IgG titers (exceeding the upper threshold) were less abundant in CMV-seropositive Belgian N2 population samples than in CMV-seropositive UK HZ patients (OR 0.51 [0.31 0.82]. We found CMVseroprevalence to increase faster with age in the UK than in other countries (P < 0.05). We conclude that CMV IgG seropositivity is associated with HZ. This finding could add to the growing list of risk factors for HZ.

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Influence of Frequent Infectious Exposures on General and Varicella-Zoster Virus-Specific Immune Responses in Pediatricians

Cited by 28 publications

References 71 publications

Multidisciplinary study of the secondary immune response in grandparents re-exposed to chickenpox

Multidisciplinary study of the secondary immune response in grandparents re-exposed to chickenpox

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

Cytomegalovirus seropositivity is associated with herpes zoster

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