Infant and adolescent hepatitis B immunization up to 1999: a global overview

Vryheid, Robert; Kane, Mark; Muller, Nancy; Schatz, Gary C.; Bezabeh, Shewit

doi:10.1016/s0264-410x(00)00239-5

Cited by 48 publications

(33 citation statements)

References 78 publications

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“…However, there are currently more than 350 million chronic carriers of HBV worldwide who are at risk of developing chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) (47). Treatment options for chronic HBV infection are limited presently.…”

Section: Chronic Hepatitis B Virus (Hbv) Infection Is Often Associatedmentioning

confidence: 99%

Chemoimmunotherapy of Chronic Hepatitis B Virus Infection in the Woodchuck Model Overcomes Immunologic Tolerance and Restores T-Cell Responses to Pre-S and S Regions of the Viral Envelope Protein

Menne

Tennant

Gerin

et al. 2007

J Virol

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Treatment of chronic hepatitis B virus (HBV) infection could combine potent antiviral drugs and therapeuticvaccines to overcome immunological tolerance and induce the recovery phenotype to protect against disease progression. Conventional vaccination of woodchucks chronically infected with the woodchuck hepatitis virus (WHV) elicited differential T-cell response profiles depending on whether or not carriers were treated with the potent antiviral drug clevudine (CLV), which significantly reduces viral and antigen loads. The differential T-cell responses defined both CLV-dependent and CLV-independent epitopes of the pre-S and S regions of the WHV envelope protein. Only combined treatment involving CLV and conventional vaccine therapeutically restored the T-cell response profile of chronic WHV carrier woodchucks to that seen in prophylactic vaccination and in recovery from acute WHV infection. The results have implications for mechanisms of immunological tolerance operating in chronic HBV infection and suggest that such combined chemoimmunotherapy may be useful for treatment of humans with chronic HBV infection. Chronic hepatitis B virus (HBV) infection is often associatedwith immunological tolerance to the virus characterized by hyporesponsive T helper (Th) cells, reduced numbers of cytolytic T lymphocytes, diminished Th1-type cytokine responses, and undetectable virus-neutralizing antibodies to viral envelope proteins (3,8,9,16,20,24,27,42, 46). When HBVspecific cellular immune responses sometimes become detectable in HBV carriers, they are often suboptimal and contribute more to disease progression than to viral clearance and recovery (8,16,27, 46). Immunological tolerance in chronic HBV infection (2,4,6,7,37,38) may arise theoretically from central or peripheral tolerance mechanisms (or both). Central tolerance could involve negative selection of antigen-specific T cells by thymic deletion in the presence of antigen (6,7,37,38). Peripheral tolerance may follow after positive selection of antigen-specific T cells and result from clonal anergy, immunological exhaustion, or altered regulation between Th1 and Th2 cells (1, 43). The development and/or maintenance of central and peripheral tolerance in chronic HBV infection may be a consequence of the high viral and antigen loads often observed in chronic carriers. The development of immunotherapeutics able to circumvent T-cell tolerance, alone or in combination with antiviral therapeutics, represents a further critical step toward the successful treatment of chronic HBV infection.Vaccines for HBV will ultimately interdict transmission of the virus and eradicate HBV-related diseases. However, there are currently more than 350 million chronic carriers of HBV worldwide who are at risk of developing chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) (47). Treatment options for chronic HBV infection are limited presently. Pegylated alpha interferon brings about sustained antiviral responses in approximately one-third of patients (25) but is associated with ...

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Section: Chronic Hepatitis B Virus (Hbv) Infection Is Often Associatedmentioning

confidence: 99%

Chemoimmunotherapy of Chronic Hepatitis B Virus Infection in the Woodchuck Model Overcomes Immunologic Tolerance and Restores T-Cell Responses to Pre-S and S Regions of the Viral Envelope Protein

Menne

Tennant

Gerin

et al. 2007

J Virol

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“…Chronic infection with the hepatitis B virus (HBV) is a major public health problem and is responsible for 1.2 million deaths per year worldwide (45). It is estimated that more than 2 billion people worldwide have serological evidence of previous or current HBV infection and that there are over 350 million chronic carriers of HBV (45).…”

Section: (؊)-␤-D-2-aminopurine Dioxolane (Apd) Is a Nucleoside Prodrumentioning

confidence: 99%

Antiviral Effect of Orally Administered (−)-β-d-2-Aminopurine Dioxolane in Woodchucks with Chronic Woodchuck Hepatitis Virus Infection

Menne

Asif

Narayanasamy

et al. 2007

Antimicrob Agents Chemother

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(؊)-␤-D-2-Aminopurine dioxolane (APD) is a nucleoside prodrug that is efficiently converted to 9-(␤-D-1,3-dioxolan-4-yl)guanine (DXG). DXG has antiviral activity in vitro against hepatitis B virus (HBV) but limited aqueous solubility, making it difficult to administer orally to HBV-infected individuals. APD is more water soluble than DXG and represents a promising prodrug for the delivery of DXG. A placebo-controlled, dose-ranging efficacy and pharmacokinetic study was conducted with woodchucks that were chronically infected with woodchuck hepatitis virus (WHV). APD was efficiently converted to DXG after oral and intravenous administrations of APD, with serum concentrations of DXG being higher following oral administration than following intravenous administration, suggestive of a considerable first-pass intestinal and/or hepatic metabolism. APD administered orally at 1, 3, 10, and 30 mg/kg of body weight per day for 4 weeks produced a dose-dependent antiviral response. Doses of 3 and 10 mg/kg/day reduced serum WHV viremia by 0.4 and 0.7 log 10 copies/ml, respectively. The 30-mg/kg/day dose resulted in a more pronounced, statistically significant decline in serum WHV viremia of 1.9 log 10 copies/ml and was associated with a 1.5-fold reduction in hepatic WHV DNA. Individual woodchucks within the highest APD dose group that had declines in serum WHV surface antigen levels, WHV viremia, and hepatic WHV DNA also had reductions in hepatic WHV RNA. There was a prompt recrudescence of WHV viremia following drug withdrawal. Therefore, oral administration of APD for 4 weeks was safe in the woodchuck model of chronic HBV infection, and the effect on serum WHV viremia was dose dependent.Chronic infection with the hepatitis B virus (HBV) is a major public health problem and is responsible for 1.2 million deaths per year worldwide (45). It is estimated that more than 2 billion people worldwide have serological evidence of previous or current HBV infection and that there are over 350 million chronic carriers of HBV (45). Carriers of HBV are at high risk of developing chronic hepatitis, hepatic cirrhosis, and hepatocellular carcinoma (HCC). Although safe and effective prophylactic vaccines against HBV are available, improvements in drug and/or immunotherapeutic strategies for the treatment of chronic HBV infection are still needed. Therapy with (pegylated) alpha interferon and nucleoside analogues, alone or in combination, can be effective against HBV. However, side effects of interferon and the emergence of nucleoside-resistant mutants often limit treatment outcomes (26, 36). Therefore, there is a continued need for the development of new antiviral compounds for the treatment of chronic HBV infection.(Ϫ)-␤-D-2-Aminopurine dioxolane [APD; (Ϫ)-(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)-2-aminopurine] is a purine nucleoside prodrug that is efficiently converted in vivo to the nucleoside 9-(␤-D-1,3-dioxolan-4-yl)guanine (DXG) following intravenous and/or oral administration in mice and rhesus monkeys (2, 25) (Fig. 1). Biotrans...

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“…Discovery of the virus, development of plasmaderived and then DNA-recombinant vaccines, and reductions in vaccine prices have made the wide use of this vaccine possible. 4 Hepatitis B vaccine given in infancy is highly effective in preventing HBV infection. 5 The WHO has recommended hepatitis B vaccination in the Expanded Programme on Immunization This double-blind, randomized study evaluated the immunogenicity and safety of three production lots of the fully liquid combination DTwp-Hep-Hib vaccine, Quinvaxem ® (crucell, The Netherlands) in 360 healthy infants aged 42-64 d old given at 6, 10 and 14 weeks of age (core study).…”

Section: Introductionmentioning

confidence: 99%

Lot-to-lot consistency study of the fully liquid pentavalent DTwP-HepB-Hib vaccine Quinvaxem ^® demonstrating clinical equivalence, suitability of the vaccine as a booster and concomitant administration with measles vaccine

Aspinall

Traynor

Bedford³

et al. 2012

Human Vaccines & Immunotherapeutics

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Infant and adolescent hepatitis B immunization up to 1999: a global overview

Cited by 48 publications

References 78 publications

Chemoimmunotherapy of Chronic Hepatitis B Virus Infection in the Woodchuck Model Overcomes Immunologic Tolerance and Restores T-Cell Responses to Pre-S and S Regions of the Viral Envelope Protein

Chemoimmunotherapy of Chronic Hepatitis B Virus Infection in the Woodchuck Model Overcomes Immunologic Tolerance and Restores T-Cell Responses to Pre-S and S Regions of the Viral Envelope Protein

Antiviral Effect of Orally Administered (−)-β-d-2-Aminopurine Dioxolane in Woodchucks with Chronic Woodchuck Hepatitis Virus Infection

Lot-to-lot consistency study of the fully liquid pentavalent DTwP-HepB-Hib vaccine Quinvaxem ^® demonstrating clinical equivalence, suitability of the vaccine as a booster and concomitant administration with measles vaccine

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Infant and adolescent hepatitis B immunization up to 1999: a global overview

Cited by 48 publications

References 78 publications

Chemoimmunotherapy of Chronic Hepatitis B Virus Infection in the Woodchuck Model Overcomes Immunologic Tolerance and Restores T-Cell Responses to Pre-S and S Regions of the Viral Envelope Protein

Chemoimmunotherapy of Chronic Hepatitis B Virus Infection in the Woodchuck Model Overcomes Immunologic Tolerance and Restores T-Cell Responses to Pre-S and S Regions of the Viral Envelope Protein

Antiviral Effect of Orally Administered (−)-β-d-2-Aminopurine Dioxolane in Woodchucks with Chronic Woodchuck Hepatitis Virus Infection

Lot-to-lot consistency study of the fully liquid pentavalent DTwP-HepB-Hib vaccine Quinvaxem ® demonstrating clinical equivalence, suitability of the vaccine as a booster and concomitant administration with measles vaccine

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Product

Resources

About

Lot-to-lot consistency study of the fully liquid pentavalent DTwP-HepB-Hib vaccine Quinvaxem ^® demonstrating clinical equivalence, suitability of the vaccine as a booster and concomitant administration with measles vaccine