Changes to the natural killer cell repertoire after therapeutic hepatitis B DNA vaccination.
BACKGROUND
Improvements 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.


RESULTS
In 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 CD56(bright) 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 CD56(bright) NK population. The ex vivo CD107a expression by CD56(bright) 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 CD56(bright) NK cell population were correlated with HBV-specific T cell responses detected by the ELISPOT assay.


CONCLUSIONS
These changes in the CD56(bright) 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.


BACKGROUND
ClinicalTrials.gov NCT00988767.
Scott-Algara
Daniel
D
Unité de Régulation des Infections Rétrovirales, Institut Pasteur, Paris, France.
Mancini-Bourgine
Maryline
M
Fontaine
Hélène
H
Pol
Stanislas
S
Michel
Marie-Louise
ML
D015703:Antigens, CD / Q000276:immunology; D002353:Carrier State; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006509:Hepatitis B / Q000628:therapy*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D019562:Viral Load
D015703:Antigens, CD; D017325:Hepatitis B Vaccines; D019444:Vaccines, DNA