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Arthritis Res Ther. 2019 Mar 14;21(1):75. doi: 10.1186/s13075-019-1854-6.

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

Author information

1
Departamento de Reumatologia, Hospital Universitário de Brasília, Universidade de Brasília, Brasília, DF, Brazil. ferreira.clarissa@gmail.com.
2
Grupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou, Fundação Oswaldo Cruz, FIOCRUZ-Minas, Avenida Augusto de Lima, 1715 Barro Preto, Belo Horizonte, 30190-002, Brazil. ferreira.clarissa@gmail.com.
3
Instituto René Rachou, Fundação Oswaldo Cruz - FIOCRUZ-Minas, Belo Horizonte, MG, Brazil.
4
Grupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou, Fundação Oswaldo Cruz, FIOCRUZ-Minas, Avenida Augusto de Lima, 1715 Barro Preto, Belo Horizonte, 30190-002, Brazil.
5
Departamento de Reumatologia, Hospital Universitário de Brasília, Universidade de Brasília, Brasília, DF, Brazil.
6
Instituto de Tecnologia em Imunobiológicos Bio-Manguinhos - FIOCRUZ, Rio de Janeiro, RJ, Brazil.
7
Programa Nacional de Imunizações - Secretaria de Vigilância em Saúde, Ministério da Saúde, Brasília, DF, Brazil.

Abstract

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.

KEYWORDS:

Cellular immunity; Immunomodulatory therapy; Neutralizing antibodies; Rheumatoid arthritis; Yellow fever vaccine

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