Cellular immunity in healthy volunteers treated with an octavalent conjugatePseudomonas aeruginosavaccine

Abstract

SummaryHumoral immunity in response to an octavalent O-polysaccharide-toxin A conjugate Pseudomonas aeruginosa vaccine is well studied, and a phase III clinical study in cystic fibrosis (CF) patients is currently ongoing. In contrast, little is known about cellular immunity induced by this vaccine. Fifteen healthy volunteers were immunized on days 1 and 60. Parameters of cellular immunity were studied before vaccination on day 1, and on day 74. Analyses included flow cytometry of whole blood and antigen-induced proliferation of and cytokine production by lymphocyte cultures. The effects of immunization on the composition of peripheral blood lymphocytes as determined by flow cytometry were minor. In contrast, after immunization a highly significant increase of proliferation in response to stimulation with detoxified toxin A was noted: the stimulation index rose from 1·4 on day 1 to 42·2 on day 74 (restimulation with 0·4 μ μ μ μ g/ml; P = = = = 0·003). Immunization led to significant production of interferon (IFN)-γ γ γ γ and tumour necrosis factor (TNF)-α α α α by antigen-stimulated lymphocytes. In contrast, no significant induction of interleukin (IL)-4 or IL-10 was observed. In conclusion, immunization of healthy volunteers led to activation of cellular immunity including strong antigen-specific proliferation and cytokine production. In CF patients priming of the cellular immune system towards a Th1-like pattern would be of potential advantage. Therefore, confirmatory analyses in immunized CF patients with and without chronic infection with P. aeruginosa are foreseen.

Assessment of humoral and cell-mediated immunity againstBordetella pertussisin adolescent, adult, and senior subjects in Italy

“…The stimulation index (SI ; cut-off >5) on peripheral blood mononuclear cells was assessed using a lymphocytic proliferation test against specific antigens, mitogen and control antigens [PT, tetanus toxoid (TT), and phytohaemagglutinin (PHA)] [26,27].…”

Airway infection in stable lung transplant patients is associated with decreased intracellular T‐helper type 1 pro‐inflammatory cytokines in bronchoalveolar lavage T‐cell subsets

“…There has been a report of cytokine‐modulatory activity of CD4+ splenic T cells in the mouse model by P. aeruginosa quorum‐sensing signal molecules (12), suggesting that infection with this organism may inhibit the patient's immune response. However, there have been no reports of cytokine‐modulatory activity of CD8+ T cells or by other organisms isolated from the BAL of these patients other than immunostimulatory (7, 8), suggesting that the reduced Th1 T‐cell pro‐inflammatory response by these patients is more likely due to treatment with immunosuppressants.…”

“…Although Th1 pro‐inflammatory cytokine production is important in host defense against microbial infection in the lungs, particularly Aspergillus and Pseudomonas spp., organisms shown to be the leading causes of mortality in immunocompromised patients (7–9), we hypothesized that excessive immunosuppression of these cytokines may leave patients susceptible to infection. To investigate whether infection is associated with reduced Th1 pro‐inflammatory cytokines, whole blood and BAL samples from 13 stable lung transplant patients with ‘culture‐negative’ BAL and 13 patients with ‘culture‐positive’ BAL were stimulated in vitro , and cytokine production by CD8+ and CD4+ T‐cell subsets was determined using multiparameter flow cytometry.…”

Vaccine strategies against cystic fibrosis pathogens

“…Previously, an assay was performed in humans with O-polysaccharide conjugated to toxin A and vaccinated children developed less chronic Pseudomonas lung infections than non-vaccinated children. 45,46 An element of alginate (polymannuronic acid) has also been conjugated to flagellin leading to protective efficacy in a mouse lung infection model. 47 Some P. aeruginosa antigens conjugated to bovine serum albumin have also been tested in mice.…”