Changes to the Natural Killer Cell Repertoire after Therapeutic Hepatitis B DNA Vaccination

Abstract

BackgroundImprovements to the outcome of adaptive immune responses could be achieved by inducing specific natural killer (NK) cell subsets which can cooperate with dendritic cells to select efficient T cell responses. We previously reported the induction or reactivation of T cell responses in chronic hepatitis B patients vaccinated with a DNA encoding hepatitis B envelope proteins during a phase I clinical trial.Methodology/Principal FindingsIn this study, we examined changes in the peripheral NK cell populations occurring during this vaccine trial using flow cytometry analysis. Despite a constant number of NK cells in the periphery, a significant increase in the CD56bright population was observed after each vaccination and during the follow up. Among the 13 different NK cell markers studied by flow cytometry analysis, the expression of CD244 and NKG2D increased significantly in the CD56bright NK population. The ex vivo CD107a expression by CD56bright NK cells progressively increased in the vaccinated patients to reach levels that were significantly higher compared to chronically HBV-infected controls. Furthermore, modifications to the percentage of the CD56bright NK cell population were correlated with HBV-specific T cell responses detected by the ELISPOT assay.Conclusions/SignificanceThese changes in the CD56bright population may suggest a NK helper effect on T cell adaptive responses. Activation of the innate and adaptive arms of the immune system by DNA immunization may be of particular importance to the efficacy of therapeutic interventions in a context of chronic infections.Trial RegistrationClinicalTrials.gov NCT00988767

Boosting vaccine efficacy the natural (killer) way

“…This supports data in mouse models of chronic LCMV infection that reveal NK cell-depletion to be an effective means of reinvigorating dysnfuntional virus-specific T cells to promote viral control [117]. However, during therapeutic vaccination of hepatitis B virus-infected patients, an increase in the proportion of CD56 bright NK cells was associated with an enhanced HBV-specific T cell response [118]. Furthermore, conventional wisdom holds that NK cells contribute to the immune response against HIV, HCV, and cancer [119].…”

Plasmid Vector-Linked Maturation of Natural Killer (NK) Cells Is Coupled to Antigen-Dependent NK Cell Activation during DNA-Based Immunization in Mice

“…The timing of analysis is also important, and indeed our previous results showed an increase in the CD56 bright NK cell subset when measured 1 month after DNA injection into patients (48). Considered to be abundant cytokine producers but weakly cytotoxic, human CD56 bright NK cells are functionally different from the murine Mac-1 ϩ…”

“…This plasmid DNA vaccine also activated innate cells, such as CD56 bright NK cells, in chronic HBV patients. Interestingly, the activation of NK cells correlated with vaccine-activated T cell responses (48).…”

Antiviral Treatment Alters the Frequency of Activating and Inhibitory Receptor-Expressing Natural Killer Cells in Chronic Hepatitis B Virus Infected Patients

“…Several groups have studied NK cells during the antiviral treatment of CHB patients, but the results regarding NK cell frequency and receptor expression are conflicting [32, 40, 41]. This probably reflects the complexity of activating and inhibiting signals that control NK cells.…”