NDLI: Efficacy of hepatitis B vaccine against antiviral drug-resistant hepatitis B virus mutants in the chimpanzee model.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kamili, Saleem Sozzi, Vitini Thompson, Geoff Campbell, Katie Walker, Christopher M. Locarnini, Stephen Krawczynski, Krzysztof
Description	Country affiliation: United States Author Affiliation: Kamili S ( Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.)
Abstract	UNLABELLED: Hepatitis B virus (HBV) mutants resistant to treatment with nucleoside or nucleotide analogs and those with the ability to escape from HBV-neutralizing antibody have the potential to infect HBV-vaccinated individuals. To address this potential serious public health challenge, we tested the efficacy of immunity induced by a commercial hepatitis B vaccine against a tissue culture-derived, clonal HBV polymerase mutant in HBV seronegative chimpanzees. The polymerase gene mutant contained a combination of three mutations (rtV173L, rtL180M, rtM204V), two of which resulted in changes to the overlapping viral envelope of the hepatitis B surface antigen (sE164D, sI195M). Prior to the HBV mutant challenge of vaccinated chimpanzees, we established virologic, serologic, and pathologic characteristics of infections resulting from intravenous inoculation of the HBV polymerase gene mutant and the sG145R vaccine-escape surface gene mutant. Cloning and sequencing experiments determined that the three mutations in the polymerase gene mutant remained stable and that the single mutation in the surface gene mutant reverted to the wild-type sequence. Immunological evidence of HBV replication was observed in the vaccinated chimpanzees after challenge with the polymerase gene mutant as well as after rechallenge with serum-derived wild-type HBV (5,000 chimpanzee infectious doses administered intravenously), despite robust humoral and cellular anti-HBV immune responses after hepatitis B vaccination. CONCLUSION: Our data showing successful experimental infection by HBV mutants despite the presence of high anti-HBs levels considered protective in the vaccinated host are consistent with clinical reports on breakthrough infection in anti-HBs-positive patients infected with HBV mutants. In the absence of a protective humoral immunity, adaptive cellular immune responses elicited by infection may limit HBV replication and persistence.
File Format	HTM / HTML
ISSN	02709139
Issue Number	5
Volume Number	49
e-ISSN	15273350
Journal	Hepatology
Language	English
Publisher	Wiley
Publisher Date	2009-05-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Discipline Hepatology Gene Products, Pol Genetics Hepatitis B Vaccines Immunology Hepatitis B Virus Drug Effects Pan Troglodytes Rna-directed Dna Polymerase Animals Drug Resistance, Viral Female Male Mutation Vaccines, Synthetic Viral Proteins Evaluation Studies Journal Article
Content Type	Text
Resource Type	Article
Subject	Hepatology

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