Abstract
ObjectiveTo explore whether a prime-boost vaccination strategy, i.e., a dose of pneumococcal conjugate vaccine (PCV) and a dose of 23-valent polysaccharide vaccine (PPV23), enhances antibody response compared to single PCV dose in patients with inflammatory rheumatic diseases treated with different immunosuppressive drugs and controls.MethodsPatients receiving rituximab (n = 30), abatacept (n = 23), monotherapy with conventional disease-modifying antirheumatic drugs (cDMARDs, methotrexate/azathioprine/mycophenolate mofetil, n = 27), and controls (n = 28) were immunized with a dose PCV followed by PPV23 after ≥ 8 weeks. Specific antibodies to 12 serotypes included in both vaccines were determined using a multiplex microsphere immunoassay in blood samples before and 4–8 weeks after each vaccination. Positive antibody response was defined as ≥ 2-fold increase from pre- to postvaccination serotype-specific IgG concentration and putative protective level as IgG ≥ 1.3 μg/mL. The number of serotypes with positive antibody response and IgG ≥ 1.3 μg/mL, respectively, after PCV and PCV + PPV23 were compared within each treatment group and to controls. Opsonophagocytic activity (OPA) assay was performed for serotypes 6B and 23F.ResultsCompared to single-dose PCV, prime-boost vaccination increased the number of serotypes with positive antibody response in patients with abatacept, cDMARDs, and controls (p = 0.02, p = 0.01, and p = 0.01), but not in patients on rituximab. After PCV + PPV23, the number of serotypes with positive antibody response was significantly lower in all treatment groups compared to controls but lowest in rituximab, followed by the abatacept and cDMARD group (p < 0.001). Compared to PCV alone, the number of serotypes with putative protective levels after PCV + PPV23 increased significantly only in patients in cDMARDs (p = 0.03) and controls (p = 0.001). Rituximab treatment was associated with large reduction (coefficient − 8.6, p < 0.001) and abatacept or cDMARD with moderate reductions (coefficients − 1.9 and − 1.8, p = 0.005, and p < 0.001) in the number of serotypes with positive antibody response to PCV + PPV23 (multivariate linear regression model). OPA was reduced in rituximab (Pn6B and Pn23F, p < 0.001), abatacept (Pn23F, p = 0.02), and cDMARD groups (Pn6B, p = 0.02) compared to controls.ConclusionsPrime-boost strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients with inflammatory rheumatic diseases receiving cDMARDs, to some extent in abatacept but not in patients on rituximab. Pneumococcal vaccination should be encouraged before the initiation of treatment with rituximab.Trial registrationClinicalTrials.gov, NCT03762824. Registered on 4 December 2018, retrospectively registered
Highlights
Infection, in particular pneumonia, is an important cause of the excess mortality in patients with rheumatoid arthritis [1]
Prime-boost strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients with inflammatory rheumatic diseases receiving cDMARDs, to some extent in abatacept but not in patients on rituximab
The introduction of 7valent pneumococcal conjugate vaccine (PCV7) followed by PCV13 into childhood vaccination programs worldwide resulted in herd protective effects [3] and shifts toward Invasive pneumococcal disease (IPD) caused by non-PCV13 serotypes, i.e., serotype replacement has been reported from several countries [4,5,6]
Summary
In particular pneumonia, is an important cause of the excess mortality in patients with rheumatoid arthritis [1]. Invasive pneumococcal disease (IPD), caused by Streptococcus pneumoniae, is a vaccine-preventable lifethreatening condition. Two pneumococcal vaccines are currently available for immunization of adults, the 23-valent pneumococcal polysaccharide (PPV23) and the 13-valent conjugate vaccine (PCV13). The introduction of 7valent pneumococcal conjugate vaccine (PCV7) followed by PCV13 into childhood vaccination programs worldwide resulted in herd protective effects [3] and shifts toward IPD caused by non-PCV13 serotypes, i.e., serotype replacement has been reported from several countries [4,5,6]. A large randomized placebo-controlled trial of adults ≥ 65 years demonstrated that PCV13 effectively prevented vaccine-type IPD and pneumococcal pneumonia in 75% and 45%, respectively [7]. Among all IPD cases in Sweden in 2017, PCV13-serotypes accounted for only 30%, but 65% of infections were caused by serotypes included in PPV23 [8]. Since 2012, the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP)
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