Journal Article

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

Martins-Filho, Olindo Assis, da Costa-Rocha, Ismael Artur, Oliveira, Ana Cristina Vanderley, Peruhype-Magalhāes, Vanessa, Coelho-dos-Reis, Jordana Grazziela, de Lima, Sheila Maria Barbosa, Domingues, Carla Magda, da Mota, Lícia Maria Henrique, Ferreira, Clarissa de Castro, Freire, Larissa Chaves, Teixeira-Carvalho, Andréa, Campi-Azevedo, Ana Carolina, Antonelli, Lis Ribeiro do Valle, Torres, Karen, Maia, Maria de Lourdes de Sousa

2019

Overview

Background The 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. Methods A 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. Results The 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. Conclusions These 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 registration RBR-946bv5 . Date of registration: March 05, 2018. Retrospectively registered

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult / Aged / Aged, 80 and over / Analysis / Antiarthritic agents / Antibodies, Neutralizing / Antirheumatic agents / Antirheumatic Agents - therapeutic use / Arthritis / Arthritis, Rheumatoid - immunology / Arthritis, Rheumatoid - therapy / Cellular immunity / Collaboration / Disease / Drug dosages / Drug therapy / Female / Fever / Humans / Immunologic Memory - immunology / Immunology / Immunomodulators / Immunomodulatory therapy / Immunotherapy / Immunotherapy - methods / Infection / Lymphocytes / Male / Medicine / Medicine & Public Health / Memory / Middle Aged / Neutralizing antibodies / Orthopedics / Outcome Assessment, Health Care / Patient outcomes / Research Article / Rheumatic diseases / Rheumatoid arthritis / Rheumatoid factor / Rheumatology / T cells / Time Factors / Vaccination / Vaccination - methods / Vaccines / Yellow fever / Yellow fever vaccine / Yellow Fever Vaccine - immunology / Young Adult