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Varicella-zoster-virus vaccination in immunosuppressed children with rheumatic diseases using a pre-vaccination check list.

ABSTRACT: The goal of this study was to apply the varicella zoster virus (VZV) vaccine to patients with pediatric rheumatic diseases (PRD) at risk for severe chickenpox, without interrupting their current immunosuppression, including biological agents, using an immunological-based pre-vaccination checklist to assure safety. A pre-vaccination checklist was implemented to ensure adequate immune competence prior to immunization.This prospective study included seronegative patients (VZV-IgG ?200 mIU/ml) and patients who had previously received only a single dose of VZV vaccine. All vaccinees demonstrated clinically inactive PRD. Patients were categorized according to their actual treatment in low-intensity IS (LIIS) and high-intensity IS (HIIS) including biological therapy. The pre-vaccination checklist defined thresholds for the following basic laboratory tests: white blood cell count ?3000/mm3, lymphocytes ?1200/mm3, serum IgG ?500 mg/dl, IgM ?20 mg/dl, tetanus toxoid antibody ?0.1 IU/ml. In case of HIIS additional specifications included a CD4+ lymphocyte count ?200/mm3 and a positive T-cell function (via analyzable positive control of a standard tuberculosis interferon-gamma-release-assay (TB-IGRA) indicating mitogen-induced T cell proliferation). Patients who met the criteria of the pre-vaccination checklist received the first and/or second VZV vaccination. Immunologic response and side effects were monitored.Twenty-three patients were recruited of whom nine had already received one VZV immunization before initiating IS. All patients met the pre-vaccination checklist criteria despite ongoing IS. There was no overall difference in VZV-IgG levels when comparing the LIIS (n=9) and HIIS (n=14) groups. In total, 21 patients (91%) showed a positive vaccination response, after the first immunization the median VZV-IgG across all patients was 224 (59-1219) mIU/ml (median (range)), after booster immunization it increased to 882 (30-4685) mIU/ml. Two patients in the HIIS group failed to raise positive VZV-IgG, despite booster immunization. All nine patients receiving only the second immunization on IS reached high titers of VZV-IgG >500 mIU/ml (1117 (513-4685) mIU/ml). There were no cases of rash or other vaccine-induced varicella disease symptoms and no evidence of PRD flare.VZV vaccination is safe and largely immunogenic in children with ongoing IS fulfilling an immunological based pre-vaccination checklist. This new approach is based on immunologic function rather than on type of medications.ISRCRTN trial registration number 21654693 , date of registration February 12, 2018, retrospectively registered.

SUBMITTER: Speth F

PROVIDER: S-EPMC5833060 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Varicella-zoster-virus vaccination in immunosuppressed children with rheumatic diseases using a pre-vaccination check list.

Speth Fabian F Hinze Claas H CH Andel Susanne S Mertens Thomas T Haas Johannes-Peter JP

Pediatric rheumatology online journal 20180302 1

<h4>Background</h4>The goal of this study was to apply the varicella zoster virus (VZV) vaccine to patients with pediatric rheumatic diseases (PRD) at risk for severe chickenpox, without interrupting their current immunosuppression, including biological agents, using an immunological-based pre-vaccination checklist to assure safety. A pre-vaccination checklist was implemented to ensure adequate immune competence prior to immunization.<h4>Methods</h4>This prospective study included seronegative p ...[more]

PMID: 29499726

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Project description:Background:Prevention of infectious diseases is of high priority in the rapidly aging population. Unfortunately, vaccine responses in the elderly are frequently diminished. Timely vaccination of middle-aged adults might improve the immune responses to vaccines, although knowledge on pathogen-specific immune responses and factors affecting these responses, in middle-aged adults is currently limited. We thus investigated the immune responses after vaccination with Zostavax consisting of live-attenuated varicella zoster virus (VZV). Methods:Blood samples were taken pre-, 14?days, 28?days, and 1?year after a primary VZV vaccination (Zostavax) at middle age (N?=?53, 50-65?years of age). VZV-specific IFN?-producing cells were measured by ELISpot, activated T-cells by flow cytometry, antibody levels and cytokine responses by fluorescent bead-based multiplex immunoassays, and whole blood cellular kinetics by TruCOUNT analysis. Results:Robust short-term enhancement of the VZV-specific IFN?-producing cell numbers was observed post-vaccination in the middle-aged adults. Remarkably, long-term enhancement of VZV-specific IFN?-producing cell numbers was induced only in participants with low numbers of VZV-specific pre-vaccination IFN?-producing cells, who were significantly older. These participants also showed enhancement of VZV-specific activated CD4 T-cells, contrary to "exhausted" VZV-specific CD8 T-cells in participants with high numbers of VZV-specific pre-vaccination IFN?-producing cells. Finally, a high CD4/CD8 T-cell ratio was associated with low numbers of pre-vaccination VZV-specific IFN?-producing cells. Conclusion:These results suggest that adults in their early sixties, who showed a high CD4/CD8 T-cell ratio and low numbers of VZV-specific IFN?-producing cells, benefit from VZV vaccination. This provides important knowledge on factors affecting VZV-specific immune responses in middle-aged adults as well as for strategies to strengthen immunity before reaching old age.

Project description:BackgroundVaricella zoster virus (VZV) is one of the eight known human herpesviruses. Initial VZV infection results in chickenpox, while viral reactivation following a period of latency manifests as shingles. Separate vaccines exist to protect against both initial infection and subsequent reactivation. Controversy regarding chickenpox vaccination is contentious with most countries not including the vaccine in their childhood immunization schedule due to the hypothesized negative impact on immune-boosting, where VZV reactivation is suppressed through exogenous boosting of VZV antibodies from exposure to natural chickenpox infections.MethodsPopulation-level chickenpox and shingles notifications from Thailand, a country that does not vaccinate against either disease, were previously fitted with mathematical models to estimate rates of VZV transmission and reactivation. Here, multiple chickenpox and shingles vaccination scenarios were simulated and compared to a model lacking any vaccination to analyze the long-term impacts of VZV vaccination.ResultsAs expected, simulations suggested that an introduction of the chickenpox vaccine, at any coverage level, would reduce chickenpox incidence. However, chickenpox vaccine coverage levels above 35% would increase shingles incidence under realistic estimates of shingles coverage with the current length of protective immunity from the vaccine. A trade-off between chickenpox and shingles vaccination coverage was discovered, where mid-level chickenpox coverage levels were identified as the optimal target to minimize total zoster burden. Only in scenarios where shingles vaccine provided lifelong immunity or coverage exceeded current levels could large reductions in both chickenpox and shingles be achieved.ConclusionsThe complicated nature of VZV makes it impossible to select a single vaccination scenario as universal policy. Strategies focused on reducing both chickenpox and shingles incidence, but prioritizing the latter should maximize efforts towards shingles vaccination, while slowly incorporating chickenpox vaccination. Alternatively, countries may wish to minimize VZV complications of both chickenpox and shingles, which would lead to maximizing vaccine coverage levels across both diseases. Balancing the consequences of vaccination to overall health impacts, including understanding the impact of an altered mean age of infection for both chickenpox and shingles, would need to be considered prior to any vaccine introduction.

Dataset Information

Varicella-zoster-virus vaccination in immunosuppressed children with rheumatic diseases using a pre-vaccination check list.

Publications

Varicella-zoster-virus vaccination in immunosuppressed children with rheumatic diseases using a pre-vaccination check list.

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