Induction or expansion of T-cell responses by a hepatitis B DNA vaccine administered to chronic HBV carriers.
Despite the availability of effective hepatitis B vaccines for many years, over 370 million people remain persistently infected with hepatitis B virus (HBV). Viral persistence is thought to be related to poor HBV-specific T-cell responses. A phase I clinical trial was performed in chronic HBV carriers to investigate whether HBV DNA vaccination could restore T-cell responsiveness. Ten patients with chronic active hepatitis B nonresponder to approved treatments for HBV infection were given 4 intramuscular injections of 1 mg of a DNA vaccine encoding HBV envelope proteins. HBV-specific T-cell responses were assessed by proliferation, ELISpot assays, and tetramer staining. Secondary end points included safety and the monitoring of HBV viraemia and serological markers. Proliferative responses to hepatitis B surface antigen were detected in two patients after DNA injections. Few HBV-specific interferon gamma-secreting T cells were detectable before immunization, but the frequency of such responses was significantly increased by 3 DNA injections. Immunization was well tolerated. Serum HBV DNA levels decreased in 5 patients after 3 vaccine injections, and complete clearance was observed in 1 patient. In conclusion, this study provides evidence that HBV DNA vaccination is safe and immunologically effective. We demonstrate that DNA vaccination can specifically but transiently activate T-cell responses in some chronic HBV carriers who do not respond to current antiviral therapies.
Mancini-Bourgine
Maryline
M
Carcinogénèse Hépatique et Virologie Moléculaire/Institut National de la Santé et de la Recherche Médicale Unité 370, Institut Pasteur, Paris, France.
Fontaine
Hélène
H
Scott-Algara
Daniel
D
Pol
Stanislas
S
Bréchot
Christian
C
Michel
Marie-Louise
ML
D000328:Adult; D002455:Cell Division / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D017325:Hepatitis B Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma