title: Immunization with hepatitis B vaccine accelerates SLE-like disease in a murine model.
abstract: Hepatitis-B vaccine (HBVv) can prevent HBV-infection and associated liver diseases. However, concerns regarding its safety, particularly among patients with autoimmune diseases (i.e. SLE) were raised. Moreover, the aluminum adjuvant in HBVv was related to immune mediated adverse events. Therefore, we examined the effects of immunization with HBVv or alum on SLE-like disease in a murine model. NZBWF1 mice were immunized with HBVv (Engerix), or aluminum hydroxide (alum) or phosphate buffered saline (PBS) at 8 and 12 weeks of age. Mice were followed for weight, autoantibodies titers, blood counts, proteinuria, kidney histology, neurocognitive functions (novel object recognition, staircase, Y-maze and the forced swimming tests) and brain histology. Immunization with HBVv induced acceleration of kidney disease manifested by high anti-dsDNA antibodies (p < 0.01), early onset of proteinuria (p < 0.05), histological damage and deposition of HBs antigen in the kidney. Mice immunized with HBVv and/or alum had decreased cells counts mainly of the red cell lineage (p < 0.001), memory deficits (p < 0.01), and increased activated microglia in different areas of the brain compare with mice immunized with PBS. Anxiety-like behavior was more pronounced among mice immunized with alum. In conclusion, herein we report that immunization with the HBVv aggravated kidney disease in an animal model of SLE. Immunization with either HBVv or alum affected blood counts, neurocognitive functions and brain gliosis. Our data support the concept that different component of vaccines may be linked with immune and autoimmune mediated adverse events.
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 52621, Israel; Sackler Medical School, Tel Aviv University, Israel.
authors.forename: Nancy
authors.initials: N
authors.lastname: Agmon-Levin
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 52621, Israel; Doctoral Program in Biomedical Sciences Universidad del Rosario, Bogota 111221, Colombia; Center for Autoimmune Diseases Research - CREA, Universidad del Rosario, Bogota 111221, Colombia.
authors.forename: María-Teresa
authors.initials: MT
authors.lastname: Arango
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 52621, Israel; Sackler Medical School, Tel Aviv University, Israel; The Dr. Pinchas Borenstein Talpiot Medical Leadership Program 2013, Sheba Medical Center, Tel-Hashomer 52621, Israel.
authors.forename: Shaye
authors.initials: S
authors.lastname: Kivity
authors.affiliation: Department of Neurology and Sagol Neuroscience Center, Sheba Medical Center, Tel-Hashomer 52621, Israel.
authors.forename: Aviva
authors.initials: A
authors.lastname: Katzav
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 52621, Israel.
authors.forename: Boris
authors.initials: B
authors.lastname: Gilburd
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 52621, Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Blank
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 52621, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Tomer
authors.affiliation: Institute of Pathology, Sheba Medical Center, Tel Hashomer 52621, Israel.
authors.forename: Alex
authors.initials: A
authors.lastname: Volkov
authors.affiliation: Institute of Pathology, Sheba Medical Center, Tel Hashomer 52621, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
authors.affiliation: Department of Neurology and Sagol Neuroscience Center, Sheba Medical Center, Tel-Hashomer 52621, Israel.
authors.forename: Joab
authors.initials: J
authors.lastname: Chapman
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 52621, Israel; Incumbent of the Laura Schwarz-Kip Chair for Autoimmunity, Tel-Aviv University, Israel. Electronic address: shoenfel@post.tau.ac.il.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Shoenfeld
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D001921:Brain / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D017325:Hepatitis B Vaccines / Q000009:adverse effects* / Q000494:pharmacology; D008181:Lupus Nephritis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D011507:Proteinuria / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology
chemical_list: D000974:Antibodies, Antinuclear; D017325:Hepatitis B Vaccines
keywords: Autoimmune/autoinflammatory syndrome induced by adjuvant (ASIA); Autoimmunity; Hepatitis B vaccine; Neuro-cognitive tests; SLE; Vaccination