title: Hemozoin as a novel adjuvant for inactivated whole virion influenza vaccine.
abstract: Because vaccination is an effective means to protect humans from influenza viruses, extensive efforts have been made to develop not only new vaccines, but also for new adjuvants to enhance the efficacy of existing inactivated vaccines. Here, we examined the adjuvanticity of synthetic hemozoin, a synthetic version of the malarial by-product hemozoin, on the vaccine efficacy of inactivated whole influenza viruses in a mouse model. We found that mice immunized twice with hemozoin-adjuvanted inactivated A/California/04/2009 (H1N1pdm09) or A/Vietnam/1203/2004 (H5N1) virus elicited higher virus-specific antibody responses than did mice immunized with non-adjuvanted counterparts. Furthermore, mice immunized with hemozoin-adjuvanted inactivated viruses were better protected from lethal challenge with influenza viruses than were mice immunized with non-adjuvanted inactivated vaccines. Our results show that hemozoin improves the immunogenicity of inactivated influenza viruses, and is thus a promising adjuvant for inactivated whole virion influenza vaccines.
authors.affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Uraki
authors.affiliation: Influenza Research Institute, Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors.forename: Subash C
authors.initials: SC
authors.lastname: Das
authors.affiliation: Influenza Research Institute, Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors.forename: Masato
authors.initials: M
authors.lastname: Hatta
authors.affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Kiso
authors.affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Iwatsuki-Horimoto
authors.affiliation: Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan; Transboundary Animal Diseases Center, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ozawa
authors.affiliation: Laboratory of Malaria Immunology, Immunology Frontier Research Center (IFReC), Osaka University, Osaka, Japan.
authors.forename: Cevayir
authors.initials: C
authors.lastname: Coban
authors.affiliation: Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Osaka, Japan; Laboratory of Vaccine Science, IFReC, Osaka University, Osaka, Japan.
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
authors.affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Influenza Research Institute, Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA; ERATO Infection-Induced Host Responses Project (JST), Saitama 332-0012, Japan; Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. Electronic address: kawaoka@ims.u-tokyo.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006420:Hemeproteins / Q000494:pharmacology*; D053118:Influenza A Virus, H1N1 Subtype; D053124:Influenza A Virus, H5N1 Subtype; D007252:Influenza Vaccines / Q000276:immunology*; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D006420:Hemeproteins; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; C020753:hemozoin
keywords: Adjuvant; Antibody; Hemozoin; Influenza virus; Vaccine
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