Immune response to pertussis vaccine in COPD patients

Abstract

Exacerbation triggered by respiratory infection is an important cause of morbidity and mortality in chronic obstructive pulmonary disease (COPD) patients. Strategies aiming to preventing infection may have significant public health impact. Our previous study demonstrated decreased immunological response to seasonal flu vaccination in COPD patients, questioning the efficiency of other vaccines in this group of patients. We performed a prospective, monocenter, longitudinal study that evaluated the humoral and cellular responses upon pertussis vaccination. We included 13 patients with stable COPD and 8 healthy volunteers. No difference in circulating B and T cell subsets at baseline was noted. Both groups presented similar levels of TFH, plasmablasts and pertussis specific antibodies induction after vaccination. Moreover, monitoring T cell immunity after ex-vivo peptide stimulation revealed equivalent induction of functional and specific CD4+ T cells (IFNγ, TNFα and IL-2-expressing T cells) in both groups. Our results highlight the immunological efficiency of pertussis vaccination in this particularly vulnerable population and challenge the concept that COPD patients are less responsive to all immunization strategies. Healthcare providers should stress the necessity of decennial Tdap booster vaccination in COPD patients.

Figure 1

Humoral and cellular responses to Bordetella pertussis stimulation in patients with COPD compared to controls. To measure immune responses to Pertussis vaccine, blood from n = 8 control donors and n = 13 patients was withdrawn at baseline and at day 7 or 28 days upon vaccination. (A) TFH cells (CD3+ CD4+ CXCR5+ PD1+) and plasmablasts cells (CD19+ CD38+) were measured by flow cytometry (LSRII, BD Biosciences), at baseline (D0) and 7 days (D7) after pertussis vaccination in COPD patients (n = 12) and controls (n = 8). (B) Anti-pertussis circulating immunoglobulin G (anti-PT IgG) antibodies were measured using enzyme immunoassay at D0 and D7 in COPD patients (n = 11) and controls (n = 6) (Biomnis). (C) T cell specific responses were monitored with intracellular cytokine staining for IFN-γ, IL-2, TNF-α following ex vivo PBMC stimulation with Bordetella pertussis peptide pool (filamentous hemagglutinin [FHA], fimbriae 2/3 [Fim2/3], pertactin [PRN], and inactivated pertussis toxin [PT]) antigens) in patients with COPD (n = 12) and controls (n = 7). (D) Concentration of IFN-γ, IL-2, TNF-α (pg/mL) was measured in culture supernatants from COPD patients (n = 13) and controls (n = 13) using Luminex technology following manufacturer instructions (HCYTMAG-60K-PX41). Supernatants were collected on day 5 after stimulation with Bordetella pertussis peptide. Median values are shown and statistical significance was evaluated by Wilcoxon test; *P < 0.05; **P < 0.01; ***P < 0.001.