The goal of this clinical trial is to evaluate the humoral immunogenicity of the meningococcal B vaccine (MenB-4C) in pediatric patients with autoimmune rheumatic diseases (ARDs), compared to age- and sex-matched non-immunosuppressed controls.
The main questions it aims to answer are:
* To assess the influence of treatment on the response to the MenB-4C vaccine in patients with ARDs; * To evaluate the impact of the MenB-4C vaccine on disease activity in patients with ARDs; * To evaluate the safety of the MenB-4C vaccine in pediatric patients with ARDs and controls. * To evaluate the association between physical activity levels and immunogenicity after vaccination.
Participants will:
Receive the MenB-4C vaccine (Bexsero©), administered intramuscularly in the deltoid muscle, in a 2-dose schedule (0.5 mL each), 1 month apart.
All participants will have blood samples collected immediately before vaccination at the baseline visit (D0), then receive the first vaccine dose on the same day (D0). The second dose will be administered 4 weeks after the first dose (D28). Blood samples will be collected on D0, D28, and D56. A final sample will be collected one year after the last dose (D208) to evaluate the persistence of immune response.
At study entry and one month after each dose, patients will also be assessed for clinical and laboratory disease activity using disease-specific indices and scores.
* Juvenile Systemic lupus erythematosus (JSLE): Systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) (CBC, anti-dsDNA, complement, urinalysis, protein/creatinine ratio) * Juvenile Idiopatic Arthritis (JIA): Juvenile Arthritis Disease Activity Score (JADAS) (ESR, CRP) * Juvenile dermatomyositis (JDM): Manual Muscle Testing (MMT) e Childhood Myositis Assessment Scale (CMAS): (CPK, transaminases, LDH)
Researcher will also perform analysis in:
Humoral immunogenicity will be assessed using serum bactericidal activity (SBA) assay with exogenous complement (baby rabbit, Pel Freez) against four test strains: H44/76 (fHBP), 5/99 (NadA), NZ98/254 (PorA), and M10713 (NHBA), from blood samples collected at D0, D28, D56, and D208. SBA assays will be conducted at the Immunology Center of the Adolfo Lutz Institute, São Paulo. Exogenous complement will be added to serially diluted serum samples, followed by the addition of a bacterial suspension. The humoral response rate induced by the vaccine, or seroconversion, will be defined by the bactericidal titer (the dilution that results in 50% bacterial killing within 60 minutes compared to the control), with titers ≥ 1:4 considered bactericidal. The geometric mean titers will be calculated using the exponential of the mean of the log-transformed concentrations.
Immunosuppressive treatments (NSAIDs, prednisone/prednisolone, intra-articular steroids, hydroxychloroquine, methotrexate, azathioprine, leflunomide, cyclosporine, tacrolimus, mycophenolate mofetil, and biologics \[anti-TNF, tocilizumab, abatacept, belimumab, rituximab\]) will be recorded sistematicaly.
Physical activity levels will be assessed using validated, age-appropriate methods.
Participants must be between 2 and 25 years of age with no prior history of MenB-4C vaccination.
Patients classified with autoimmune rheumatic diseases will be invited to participate.
History of any reaction or hypersensitivity to any vaccine component;
Acute infectious disease and/or fever at the time of vaccination;
Pregnancy or breastfeeding;
History of Guillain-Barré syndrome;
Parallel
Meningococcal B (Bexsero)
Biological/VaccineThe MenB-4C vaccine consists of three recombinant antigenic proteins: Neisseria meningitidis Neisseria adhesin A (NadA), factor H binding protein subfamily B (FHbp-B), and Neisseria heparin-binding antigen (NHBA), along with outer membrane vesicles (OMVs) expressing porin A (PorA) protein from serosubtype P1.4. The MenB-4C vaccine will be administered intramuscularly (into the deltoid muscle) in 2 doses of 0.5 mL each, one month apart.
Seroconversion Rate After Vaccination
Proportion of participants who achieve seroconversion. The humoral response rate induced by the vaccine, or seroconversion, will be defined by the bactericidal titer (the dilution resulting in 50% bacterial killing within 60 minutes compared to the control). Titers ≥ 1:4 will be considered bactericidal. The geometric mean titer will be calculated using the exponential of the mean of log-transformed concentrations.
Influence of Immunosuppressive Treatment on the response to MenB-4C vaccination
To assess the short- and long-term influence of immunosuppressive treatment on the response to MenB-4C vaccination in patients with ARDs compared to healthy controls. Humoral immunogenicity will be evaluated using the serum bactericidal activity (SBA) assay with exogenous complement (Baby rabbit, Pel Freez) against 4 test strains: H44/76 (fHBP vaccine antigen evaluation), 5/99 (Neisseria adhesin A), NZ98/254 (Porin A) and M10713 (NHBA).
Impact of MenB-4C vaccination on Disease Activity on patients with JIA
To evaluate the impact of MenB-4C vaccination on clinical disease activity in patients with JIA, measured using JADAS27, higher scores indicates greater disease activity. Unit of Measure: Score (0-57).
Impact of MenB-4C vaccination on Disease Activity on patients with JSLE
To evaluate the impact of MenB-4C vaccination on clinical and laboratory disease activity in patients with juvenile systemic lupus erythematosus (jSLE), assessed using the SLEDAI-2K. The score incorporates clinical and laboratory manifestations of lupus, with higher scores indicating greater disease activity. Unit of Measure: Score (range 0-105).
Impact of MenB-4c vaccination on Disease Activity on patients with JDM
To evaluate the impact of MenB-4C vaccination on clinical and laboratory disease activity in patients with juvenile dermatomyositis (JDM), assessed using the Childhood Myositis Assessment Scale (CMAS). The CMAS evaluates muscle function and endurance, with higher scores indicating better muscle strength and physical performance. Unit of Measure: Score (range 0-52).
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University of Sao Paulo General Hospital
Lead sponsor
Insituto Adolfo Lutz
Collaborator
