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ID
Source
Brief title
Health condition
Immunocompromised; HIV; Immunosuppressive medication; Stem cell transplantation; Organ transplantation; rheumatic diseases; inflammatory bowel disease; Vaccine; Vaccination; Hepatitis A vaccine; Pneumococcal vaccine; Immunogenicity
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Hepatitis A arm: Seroconversion rate, defined as the proportion of vaccinated patients with a post-immunization antibody GMC ≥10 mIU/ml in ICPs and healthy individuals 2 months after each vaccination.
- Pneumococcal arm: Seroconversion rate defined as the proportion of patients with a post-immunization antibody concentration of ≥1.3 µg/ml for 70% of all measured serotypes in ICPs and controls 2 months after the full vaccination schedule.
Secondary outcome
1. Geometric mean concentratioms (GMCs) of hepatitis A antibodies measured before and at different time points after vaccination in ICPs and controls.
2. GMCs of hepatitis A antibodies in previously fully vaccinated ICPs and controls at related to the time interval between vaccination and titer assessment.
3. Seroconversion rate in previously partially and fully vaccinated ICPs and controls defined as the proportion of vaccinated patients with a post-immunization antibody GMC ≥10 mIU/ml.
4. Differences in seroconversion rates and GMCs between ICPs and controls at the different time points.
- Pneumococcal arm
1. GMCs of serotype specific pneumococcal antibodies against individual vaccine serotypes present in PCV13 and PPSV23 in ICPs and controls and fold changes compared to baseline antibody concentrations
2. Changes in seroconversion rate and GMCs over time
3. B and T-cell responses measured at different time points.
4. Differences in seroconversion rates, GMCs, and cellular immune response between ICPs and controls at the different time points.
- Associations:
1. The influence of three different categories of immunosuppressive drugs and the degree of immunosuppression based on dose and number of immunosuppressive drugs on primary and secondary endpoints.
2. The influence of CD4+ count and use of cART in HIV patients on the primary and secondary endpoints.
3. The influence of age, sex, and intoxications (smoking/alcohol) on the primary and secondary endpoints.
Background summary
Immunocompromised patients (ICPs) are at increased risk of infections some of which are preventable by vaccination. However ICPs are also less likely to mount an effective post-vaccination immune response, leading to a clinical paradox: precisely this patient group that would most benefit vaccination is the least likely to produce an effective immune response. In this prospective cohort study the response to hepatitis A and pneumococcal vaccination will be characterized in adults using immunosuppressive agents, people living with HIV and following hematopoietic stem cell transplantation. Serum and PBMCs will collected at fixed time points. before and after vaccination. Data in this study will be used to improve vaccination guidelines for ICPs.
Study objective
Immunocompromised patients (ICPs) are at increased risk of infections, some of which are preventable by vaccination. However, ICPs are also less likely to mount effective post-vaccination immune responses, leading to a clinical paradox: precisely this patient group that most needs protection is least likely to produce a protective immune response.
Study design
- Antibody assessment hepatitis A arm: 0, 2, 6, 8, 12, 3 years months after first vaccination
- Antibody assesment pneumococcal arm: 0,2,4,6, 12, 3 years months after vaccination.
- Antibody assesment after revaccination in patients who underwent stem cell transplantation: 0, 4, 8, 10, 12 months, 3 years.
- PBMC isolation: 0,2,4 months after first pneumococcal vaccination.
Intervention
- Vaccination according to the guidelines (2 doses of inactivated hepatitis A vaccine at 0 and 6 months; One dose of prevenar13 at 0 and one dose of pneumovax23 at 2 months; after allogeneic SCT Prevenar13 at 0,1,2 and 8 months and Pneumovax23 at 10 months)
- Blood withdrawal for antibody assessment and PBMC isolation before and at different time points after vaccination
- Long term follow up (beyond the scope of this trial)
M.P. Grobusch
Amsterdam 1100 DD
The Netherlands
+31 (0)20 5664380
m.p.grobusch@amc.uva.nl
M.P. Grobusch
Amsterdam 1100 DD
The Netherlands
+31 (0)20 5664380
m.p.grobusch@amc.uva.nl
Inclusion criteria
o Indication for hepatitis A and/or or pneumococcal vaccination
o Age 18-70 years old
o At least one of the following criteria:
1. Diagnosed with HIV; and/or
2. Treated with one or more immunosuppressive agent(s); if only treated with corticosteroids, daily dose should be (the equivalent of) > 10 mg prednisolone
3. Haematopoietic stem cell transplant (HSCT) recipients months after allogeneic HSCT.
o Being able and willing to consent
- Control group:
o Immunocompetent individuals aged 18-65 years
o Indication for hepatitis A and/or or pneumococcal vaccination
o Able and willing to consent
Exclusion criteria
o Diagnosis of one of the following
1. Primary immune deficiency disorder
2. Active malignancy
3. Hemophilic disorder precluding intramuscular vaccination
4. Asplenia or haemoglobinopathy
o Receiving chemotherapy
o Autologous HSCT recipient
o Allergy to any of the components of the hepatitis A or pneumococcal vaccines
o Naturally acquired hepatitis A immunity (either assessed in the medical history or at first antibody concentration measurement)
o Previous vaccination with any pneumococcal conjugate vaccine
o Previous vaccination with pneumococcal polysaccharide vaccine (Pneumovax®) <5 years before enrollment
o Donor lymphocyte infusion < 28 days
o Pregnancy
o Not being able or willing to consent
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL7193 |
| NTR-old | NTR7385 |
| CCMO | NL65687.018.18 |
| OMON | NL-OMON56421 |