Impact of synthetic and biological immunomodulatory therapy on the duration of 17DD yellow fever vaccine-induced immunity in rheumatoid arthritis

Abstract

BackgroundThe 17DD-yellow fever (YF) vaccine induces a long-lasting protective immunity, resulting from humoral and cellular immunological memory. The treatment of rheumatoid arthritis (RA) patients with disease-modifying anti-rheumatic drugs (DMARD) may affect pre-existing 17DD-vaccine protective immunity and increase the risk of acquiring YF infection. Our goal was to determine whether DMARD would affect the duration of YF-specific protective immunity in RA patients.MethodsA total of 122 RA patients, previously immunized with the 17DD-YF vaccine (1–5, 5–9, and ≥ 10 years) and currently under DMARD therapy, were enrolled in the present investigation. Immunomodulatory therapy encompasses the use of conventional synthetic DMARD alone (csDMARD) or combines with biological DMARD (cs+bDMARD). A total of 226 healthy subjects were recruited as a control group (CONT). Neutralizing antibody responses were measured by a plaque-reduction neutralization test (PRNT), and cellular immunity was evaluated by an in vitro 17DD-YF-specific peripheral blood lymphoproliferative assay.ResultsThe data demonstrated that csDMARD therapy did not affect the duration of protective immunity induced by the 17DD-YF vaccine compared to that of CONT, as both presented a significant time-dependent decline at 10 years after vaccination. Conversely, cs+bDMARD therapy induced a premature depletion in the main determinants of the vaccine protective response, with diminished PRNT seropositivity levels between 5 and 9 years and impaired effector memory in CD8+ T cells as early as 1–5 years after 17DD-YF vaccination.ConclusionsThese findings could support changing the vaccination schedule of this population, with the possibility of a planned booster dose upon the suspension of bDMARD in cases where this is allowed, even before 10 years following 17DD-YF vaccination. The benefit of a planned booster dose should be evaluated in further studies.Trial registrationRBR-946bv5. Date of registration: March 05, 2018. Retrospectively registered

Planned Yellow Fever Primary Vaccination Is Safe and Immunogenic in Patients With Autoimmune Diseases: A Prospective Non-interventional Study

“…Ferreira et al demonstrated earlier loss of humoral response, triggered by conventional synthetic DMARDs (csDMARDs), combined with biological DMARDs. This was confirmed by the critical decrease in PRNT seropositivity rate to 76%, observed at > 5–9 years post-vaccination in patients with RA receiving combined therapy, in contrast with the standard decline observed in controls and the csDMARD group 10 years after 17DD-YF vaccination ( 40 ).…”

Yellow fever control: current epidemiology and vaccination strategies

“…They compared conventional synthetic DMARD (csDMARD) and conventional synthetic plus biological DMARD (cs + bDMARD) to controls and found that only the cs + bDMARD led to an earlier decline in the vaccine response; there was lower PRNT seropositivity between 5 and 9 years and lower effector memory in CD8+ T cells as early as 1-5 years after 17DD-YF vaccination. These finding suggest that a 10-year booster dose of YF vaccine should be administered for persons receiving bDMARD, if they are able to suspend bDMARD [63].…”

“…Ferreira et al measured neutralizing antibodies by PRNT and cellular immunity by in vitro YF-specific peripheral blood lymphoproliferative assay [63]. They compared conventional synthetic DMARD (csDMARD) and conventional synthetic plus biological DMARD (cs + bDMARD) to controls and found that only the cs + bDMARD led to an earlier decline in the vaccine response; there was lower PRNT seropositivity between 5 and 9 years and lower effector memory in CD8+ T cells as early as 1-5 years after 17DD-YF vaccination.…”

Validation of a yellow fever vaccine model using data from primary vaccination in children and adults, re-vaccination and dose-response in adults and studies with immunocompromised individuals

“…This section presents the predictions of the mathematical model presented in “ Methods ” section, comparing them with experimental data from several studies conducted by the Immunobiological Technology Institute (Bio-Manguinhos)/Oswaldo Cruz Foundation (Bio-Manguinhos/FIOCRUZ), René Rachou Research Center/Oswaldo Cruz Foundation (FIOCRUZ/Minas) and University of Brasilia (UnB) on human YFV [ 3 , 19 – 25 ], such as viremia and antibody titers, 2 for distinct scenarios. For all experimental data, we present antibody interquartile range, lower limit, and upper limit.…”