Partially randomized, non-blinded trial of DNA and MVA therapeutic vaccines based on hepatitis B virus surface protein for chronic HBV infection

Autor: Dorka Awi, James S. Cavenaugh, Samuel J. McConkey, Hilton Whittle, Maimuna Mendy, Adrian V. S. Hill
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Male
lcsh:Medicine
medicine.disease_cause
0302 clinical medicine
Rabies vaccine
Vaccines
DNA
Hepatitis B e Antigens
lcsh:Science
Virology/Vaccines
0303 health sciences
Immunity
Cellular
Multidisciplinary
Vaccination
Lamivudine
virus diseases
Hepatitis B
Viral Load
3. Good health
HBeAg
Antigens
Surface
030211 gastroenterology & hepatology
Safety
Viral load
medicine.drug
Research Article
Adult
Hepatitis B virus
Adolescent
Vaccinia virus
Gastroenterology and Hepatology/Hepatology
Medication Adherence
03 medical and health sciences
Interferon-gamma
Viral Proteins
Young Adult
Antigen
Immunology/Immunity to Infections
Infectious Diseases/Viral Infections
medicine
Humans
Serologic Tests
030304 developmental biology
business.industry
lcsh:R
medicine.disease
Virology
digestive system diseases
Immunology
Chronic Disease
lcsh:Q
business
Zdroj: PLoS ONE, Vol 6, Iss 2, p e14626 (2011)
PLoS ONE
ISSN: 1932-6203
Popis: Background Chronic HBV infects 350 million people causing cancer and liver failure. We aimed to assess the safety and efficacy of plasmid DNA (pSG2.HBs) vaccine, followed by recombinant modified vaccinia virus Ankara (MVA.HBs), encoding the surface antigen of HBV as therapy for chronic HBV. A secondary goal was to characterize the immune responses. Methods Firstly 32 HBV e antigen negative (eAg–) participants were randomly assigned to one of four groups: to receive vaccines alone, lamivudine (3TC) alone, both, or neither. Later 16 eAg+ volunteers in two groups received either 3TC alone or both 3TC and vaccines. Finally, 12 eAg– and 12 eAg+ subjects were enrolled into higher-dose treatment groups. Healthy but chronically HBV-infected males between the ages of 15 – 25 who lived in the western part of The Gambia were eligible. Participants in some groups received 1 mg or 2 mg of pSG2.HBs intramuscularly twice followed by 5×107 pfu or 1.5×108 pfu of MVA.HBs intradermally at 3-weekly intervals with or without concomitant 3TC for 11–14 weeks. Intradermal rabies vaccine was administered to a negative control group. Safety was assessed clinically and biochemically. The primary measure of efficacy was a quantitative PCR assay of plasma HBV. Immunity was assessed by IFN-γ ELISpot and intracellular cytokine staining. Results Mild local and systemic adverse events were observed following the vaccines. A small shiny scar was observed in some cases after MVA.HBs. There were no significant changes in AST or ALT. HBeAg was lost in one participant in the higher-dose group. As expected, the 3TC therapy reduced viraemia levels during therapy, but the prime-boost vaccine regimen did not reduce the viraemia. The immune responses were variable. The majority of IFN-γ was made by antigen non-specific CD16+ cells (both CD3+ and CD3–). Conclusions The vaccines were well tolerated but did not control HBV infection. Trial Registration ISRCTN ISRCTN67270384
Databáze: OpenAIRE
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