Immunogenicity, safety and adverse events of sequential vaccination with a 10-valent pneumococcal conjugate vaccine (PCV10) and PPSV23 compared with PPSV23 alone in systemic lupus erythematosus.

Background: SLE has increased risk of invasive pneumococcal disease due to immune dysregulation and immunosuppression. European Alliance of Associations for Rheumatology recommendations suggest sequential vaccination with conjugate vaccine, followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23). However, data on immunogenicity of sequential vaccination in SLE are limited.

Methods: Adult patients with SLE (American College of Rheumatology 2019 criteria) with inactive disease, stable immunosuppression for 3 months and prednisolone ≤10 mg/day were included. Sequential arm received 10-valent pneumococcal conjugate vaccine, followed by PPSV23. The second arm received only PPSV23. The two cohorts were recruited independently without randomisation. Antibodies at baseline and 12-14 weeks to pneumococci (serotypes 1, 5, 6B, 14 and 19F) were measured by ELISA and opsonophagocytic assay for functional antibodies. The primary outcome was a twofold increase in 3/5 serotypes. 40 subjects were enrolled in each arm and 15 healthy adults for response to PPSV23.

Results: 35 completed the study in the PPSV23 arm and 34 in the sequential arm. Baseline parameters were comparable.Response to PPSV23 was poorer in SLE (74.28%) compared with healthy controls (100%). There was no difference in the primary outcome between sequential vaccination (82.35%, 95% CI 68% to 94%) and PPSV23 (74.28%, 95% CI 60% to 89%). All 15 non-responders were on prednisolone. Among responders, only 41/54 (76%) were on prednisolone. There was no difference in other immunosuppressive drugs. Increasing age predicted poor response on multivariable analysis in all serotypes.Major adverse events included one event of Miller Fisher variant of Guillain-Barré syndrome in the sequential arm. Minor adverse events included one each with injection-site pain, migraine, fever and fatigue after conjugate vaccine, and one with fever after PPSV23. Three minor adverse events in the PPSV23 group included one each with injection-site pain, herpes zoster, headache and fever. In the PPSV23 arm, three minor flares were seen, while in the sequential arm, one major flare and one minor flare occurred.

Interpretation: Both vaccination strategies are safe with adequate antibody response. In low- and middle-income countries, a single-dose PPSV23 may be adequate if cost negates sequential vaccination.