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Varicella-zoster-virus vaccination in immunosuppressed children with rheumatic diseases using a pre-vaccination check
Fabian Speth1, Claas H Hinze2, Susanne Andel1
1German Center for Pediatric and Adolescent Rheumatology, Gehfeldstr. 24, 82467, Garmisch-Partenkirchen, Germany.
Insights
Varicella zoster virus (VZV) vaccination is safe and effective for children with pediatric rheumatic diseases (PRD) on immunosuppression. An immunological checklist ensures vaccine safety and immunogenicity in these at-risk patients.
Area of Science:
- Immunology
- Pediatrics
- Vaccinology
Background:
- Pediatric rheumatic diseases (PRD) increase susceptibility to severe varicella (chickenpox).
- Immunosuppression (IS) in PRD patients, including biological therapies, complicates vaccination strategies.
- An immunological-based pre-vaccination checklist was developed to ensure safe VZV vaccination during ongoing IS.
Purpose of the Study:
- To evaluate the safety and immunogenicity of VZV vaccination in PRD patients undergoing immunosuppression.
- To assess the efficacy of an immunological pre-vaccination checklist in determining vaccine eligibility.
- To determine if VZV vaccination can be safely administered without interrupting immunosuppressive therapy.
Main Methods:
- Prospective study of VZV-seronegative PRD patients or those with one prior VZV vaccine dose.
- Patients categorized into low-intensity IS (LIIS) and high-intensity IS (HIIS) groups.
- Pre-vaccination checklist assessed laboratory markers (WBC, lymphocytes, IgG, IgM, tetanus antibody) and T-cell function (TB-IGRA) for HIIS patients.
Main Results:
- 23 patients enrolled; all met checklist criteria despite ongoing IS.
- 91% (21/23) demonstrated a positive VZV vaccination response.
- Median VZV-IgG levels increased significantly post-vaccination and booster.
- No vaccine-related adverse events or PRD flares observed.
Conclusions:
- VZV vaccination is safe and immunogenic in children with PRD on immunosuppression when using an immunological checklist.
- This approach prioritizes immune function over specific medication types for vaccine eligibility.
- The findings support VZV vaccination as a viable strategy to protect PRD patients from severe chickenpox.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Trial Registration Number:
ISRCRTN trial registration number 21654693 , date of registration February 12, 2018, retrospectively registered.
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