Clinical trial NCT01847781: PNEUMOCELL - Conjugated Pneumococcal Vaccination in Patients With Immunoglobulin G-deficiency
Official title: PNEUMOCELL - Conjugated Pneumococcal Vaccination in Patients With Immunoglobulin G-deficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: IgG Deficiency
Keywords: Opsonophagocytic antibodies
Cellular immunity
Vaccine immunity
Antimicrobial peptides
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2013-05-07
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The aim is to study the immune response to conjugated pneumococcal vaccination (Prevenar13) in Immunoglobulin G-deficient patients and healthy controls. Our hypothesis is that the antibody response will be impaired in patients as compared with controls. In contrast, we postulate that the cellular immune response will be intact.

Detailed description: Ten patients with Immunoglobulin G1 and/or Immunoglobulin G2 deficiency will be enrolled together with 10 age and sex- matched controls. Blood-samples will be drawn at base-line and after 1, 2 and 4 weeks post-vaccination. Serum will be analyzed for opsonophagocytic antibodies. Peripheral blood monocytic cells (PBMCs) will be isolated, frozen and later analyzed for all time-points simultaneously. PBMCs will be stimulated with vaccine-antigens for 3-5 days and cellular activation markers will be measured together with cytokines (Interferon-gamma, Interleukin (IL)-5, IL-13, IL-10, IL-17, IL-22). In addition, levels of antimicrobial peptides in nasal fluid will be measured at baseline and after 4 weeks post-vaccination.

Eligibility criteria: Inclusion Criteria:

* Immunoglobulin gamma-deficiency: Immunoglobulin gamma 1-deficiency \< 2,8 g/L and/or Immunoglobulin gamma 2-deficiency \< 1,15 g/L
* Age 18-65

Exclusion Criteria:

* Immunoglobulin gamma-substitution for 6 months prior to study inclusion
* Prevenar7 or Prevenar13 given prior to study inclusion.
* Pneumovax given during a 2 year period prior to study inclusion
* Pregnancy or planning to become pregnant during the study period (4 weeks)
* Taking part in another clinical study involving drugs or vaccinations during the study period (4 weeks).
* Taking systemic steroids, Non steroidal anti inflammatory drugs (NSAID) or immunosuppressive drugs.
* Being allergic to any substance in the vaccine.
* Acute and ongoing disease with high fever.
* Thrombocytopenia (\< 100x109/L).
* Coagulopathy
* Breastfeeding a baby
* The healthy controls should not have any disease with effects on the immune-system

Primary outcomes:
measure: Change in opsonophagocytic antibodies
timeFrame: 4 weeks post-vaccination, change from baseline
Secondary outcomes:
measure: Change in cellular immunity
timeFrame: 4 weeks post-vaccination, change from baseline
measure: Change in antimicrobial peptides
timeFrame: 4 weeks post-vaccination, change from baseline
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Immunedeficiency Unit, Karolinska University Hospital, Huddinge
Study officials:
affiliation: Karolinska University Hospital
name: Peter W Bergman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zangenah S, Bjorkhem-Bergman L, Norlin AC, Hansen S, Lindqvist L, Henriques-Normark B, Bergman P. The Pneumocell-study: Vaccination of IgG1- and IgG2-deficient patients with Prevnar13. Vaccine. 2017 May 9;35(20):2654-2660. doi: 10.1016/j.vaccine.2017.03.097. Epub 2017 Apr 11.