title: Immunostimulatory potential of hepatitis B nucleocapsid preparations: lipopolysaccharide contamination should not be overlooked.
abstract: The nucleocapsid of hepatitis B virus (HBV) allows insertions of heterologous peptides and even complete proteins. Because of its outstanding capacity to induce B-cell, T-helper and cytotoxic T-cell responses, this structure is considered to be an important instrument for future vaccine development. Most of the evidence for the unique immunogenic qualities of nucleocapsids has been generated in mice, which are not natural hosts of HBV. Moreover, most nucleocapsid preparations used in these studies were produced in a recombinant manner in Escherichia coli. Such preparations have been shown to contain lipopolysaccharide (LPS). Not unexpectedly, it is shown here that contaminating LPS, rather than the nucleocapsid structure itself, is responsible for the activation of human antigen-presenting cells. Careful examination of the literature dealing with the immunogenicity of HBV nucleocapsids suggests that the possible presence of LPS has been largely ignored or underestimated in several studies. This raises doubts on some of the underlying mechanisms that have been proposed to explain the unique immunogenicity of the HBV nucleocapsid.
authors.affiliation: Virus Host Interactions Unit, Center for Vaccinology, Department of Clinical Biology, Microbiology and Immunology, Faculty of Medicine and Health Sciences, Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Vanlandschoot
authors.affiliation: Virus Host Interactions Unit, Center for Vaccinology, Department of Clinical Biology, Microbiology and Immunology, Faculty of Medicine and Health Sciences, Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Freya
authors.initials: F
authors.lastname: Van Houtte
authors.affiliation: The Flanders Interuniversity Institute for Biotechnology, Department of Medical Protein Research (VIB9), Faculty of Medicine and Health Sciences, Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Ulrichts
authors.affiliation: The Flanders Interuniversity Institute for Biotechnology, Department of Medical Protein Research (VIB9), Faculty of Medicine and Health Sciences, Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Tavernier
authors.affiliation: Virus Host Interactions Unit, Center for Vaccinology, Department of Clinical Biology, Microbiology and Immunology, Faculty of Medicine and Health Sciences, Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
mesh_terms: D002478:Cells, Cultured; D004340:Drug Contamination; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006512:Hepatitis B Core Antigens / Q000096:biosynthesis / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear; D008070:Lipopolysaccharides / Q000276:immunology*; D008213:Lymphocyte Activation; D019251:Nucleocapsid / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism
chemical_list: D006512:Hepatitis B Core Antigens; D008070:Lipopolysaccharides; D011994:Recombinant Proteins