Prime-boost vaccination strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients receiving conventional DMARDs, to some extent in abatacept but not in rituximab-treated patients

Per Nived, Göran Jönsson, Bo Settergren, Jon Einarsson, Tor Olofsson, Charlotte Sværke Jørgensen, Lillemor Skattum, Meliha C Kapetanovic, Per Nived, Göran Jönsson, Bo Settergren, Jon Einarsson, Tor Olofsson, Charlotte Sværke Jørgensen, Lillemor Skattum, Meliha C Kapetanovic

Abstract

Objective: To 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.

Methods: Patients 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.

Results: Compared 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.

Conclusions: 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. Pneumococcal vaccination should be encouraged before the initiation of treatment with rituximab.

Trial registration: ClinicalTrials.gov, NCT03762824. Registered on 4 December 2018, retrospectively registered.

Keywords: Abatacept; Pneumococcal conjugate vaccine; Rituximab; Synthetic disease-modifying antirheumatic drugs.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Schematic of PCV and PPV23 immunizations and blood samples in treatment groups and controls
Fig. 2
Fig. 2
The number of serotypes with positive antibody response after PCV13 and PCV13 + PPV23 in treatment groups and controls
Fig. 3
Fig. 3
The number of serotypes with putative protective levels (i.e., specific IgG concentration ≥ 1.3 μg/mL) after PCV13 and PCV13 + PPV23 in treatment groups and controls
Fig. 4
Fig. 4
Proportion of phagocytes with uptake of pneumococcal serotype 6B (a) and serotype 23F (b)

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