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THU0245 Post-Vaccinal Arthritis in an Ebola Vaccine Trial with a Live-Attenuated Recombinant Virus Expressing the Ebola Surface Glycoprotein (RVSV-ZEBOV)
  1. A. Finckh1,
  2. S. Yerly2,
  3. J.-A. Dayer3,
  4. A. Huttner3,
  5. I. Lazarou4,
  6. I. Fabreguet4,
  7. J. Berner4,
  8. L. Tapparel4,
  9. L. Kaiser3,
  10. C. Gabay4,
  11. C.-A. Siegrist5,6
  1. 1Geneva University Hospital, Geneva, Switzerland
  2. 2Virology Laboratory
  3. 3Division of Infectious Diseases
  4. 4Rheumatology
  5. 5Vaccinology, Geneva University Hospital
  6. 6WHO Collaborative Center for Vaccinology, Faculty of Medicine, Geneva, Switzerland

Abstract

Background The recent ebolavirus outbreak is a global public health concern, warranting the development of safe and effective vaccines. A live-attenuated recombinant vesicular stomatitis virus expressing the Ebola virus surface glucoprotein (rVSV-ZEBOV) is one of the promising candidate vaccines. Under the coordination of the World Health Organization, the VSV-Ebola Consortium initiated a trial to assess the safety of various doses of rVSV-ZEBOV.

Objectives To describe rheumatic adverse events following rVSV-ZEBOV vaccination.

Methods Investigator-driven phase I/II, dose-finding, placebo-controlled, double blind trial of rVSV-ZEBOV at 107 or 5x107 pfu or placebo. Subjects with incident rheumatic symptoms were referred to a rheumatologist for a standardized workup including imaging.

Results 59 subjects received either rVSV-ZEBOV (n=51) or placebo (n=8). Baseline characteristics did not differ among treatment groups. Mild to moderate early-onset reactogenicity was frequent (50/51 vaccinees, 98%), with early low grade fevers, headaches and myalgias that vanished promptly (median 1 day). Low-level rVSV RNA was detected in plasma only on days 1 and 3.

Unexpectedly, 11/59 subjects (19%) experienced acute inflammatory arthralgias at a median of 11 days after vaccination (IQR: 9 – 13). Eight presented with asymmetrical and migratory involvement of peripheral joints (median 2.5 (range 1-4)), and three with axial disease. Synovitis and tenosynovitis could be confirmed by ultrasound in 7/8 subjects with peripheral arthritis and MRI demonstrated an interspinal bursitis in 1/3 subjects with axial involvement. Acute-phase reactants were not elevated, HLA B-27 prevalence was not increased (10%), and no elevation in auto-antibodies was observed. Arthralgias were self-limited, lasting on average 11 days (IQR: 8-18). Functional impact was moderate (median RAPID3 score: 2.5, IQR: 1.8-3.3) and disease activity low (median DAS44: 1.8, IQR: 1.7-2.0). Three vaccinees also experienced a diffuse maculo-papular skin rash with small vesicles. rVSV RNA was detected in the synovial fluid (1*) and in skin vesicles (3*), but no replication of the virus could be demonstrated in the synovial fluid. Occurrence of arthritis was associated with decreased drop in lymphocyte counts at day 1 (p=0.033). All patients responded well to a limited course of NSAIDs or a single infiltration with glucocorticoids.

Conclusions The occurrence of arthritis following a symptom-free interval was unexpected and lead to a temporary suspension of the trial. Detection of rVSV RNA in the synovial fluid suggests the presence of rVSV-ZEBOV in affected joints, as reported following rubella infection or vaccination. However, no replication of rVSV-ZEBOV could be demonstrated. The most likely hypothesis is thus that rVSV-ZEBOV-induced arthritis is associated with immune-complex deposition.

Disclosure of Interest None declared

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