Safety and immunogenicity of a primary yellow fever vaccination under low-dose methotrexate therapy-a prospective multi-centre pilot study

Abstract

Background: More people on immunosuppression live in or wish to travel to yellow fever virus (YFV)-endemic areas. Data on the safety and immunogenicity of yellow fever vaccination (YFVV) during immunosuppression are scarce. The aim of this study was to compare the safety and immunogenicity of a primary YFVV between travellers on methotrexate and controls. Methods: We conducted a prospective multi-centre controlled observational study from 2015 to 2017 in six Swiss travel clinics. 15 adults (nine with rheumatic diseases, five with dermatologic conditions and one with a gastroenterological disease) on low-dose methotrexate (≤20 mg/week) requiring a primary YFVV and 15 age and sex-matched controls received a YFVV. Solicited/unsolicited adverse reactions were recorded, YFV-RNA was measured in serum samples on Days 3, 7, 10, 14, 28 and neutralizing antibodies on Days 0, 7, 10, 14, 28. Results: Patients L and controls f median ages were 53 and 52 years; 9 patients and 10 controls were female. 43% of patients and 33% of controls showed local side effects (P =0.71); 86% of patients and 66% of controls reported systemic reactions (P =0.39). YFV-RNA was detected in patients and controls on Day 3.10 post-vaccination and was never of clinical significance. Slightly more patients developed YFV-RNAaemia (Day 3: N=5 vs n=2, Day 7: N=9 vs n=7, Day 10: N=3 vs n=2, all P >0.39). No serious reactions occurred. On Day 10, a minority of vaccinees was seroprotected (patients: N=2, controls: N=6). On Day 28, all vaccinees were seroprotected. Conclusions: First-time YFVV was safe and immunogenic in travellers on low-dose methotrexate. Larger studies are needed to confirm these promising results.