Biochem Biophys Res Commun. 2019 Sep 30. pii: S0006-291X(19)31799-1. doi: 10.1016/j.bbrc.2019.09.072. [Epub ahead of print]
Intranasal vaccination with HBs and HBc protein combined with carboxyl vinyl polymer induces strong neutralizing antibody, anti-HBs IgA, and IFNG response.
Sanada T1, Yamamoto N1, Kayesh MEH2, Tsukiyama-Kohara K2, Hasegawa H3, Miyazaki T4, Takano JI5, Shiogama Y5, Yasutomi Y5, Goh Y6, Yoshida O7, Hiasa Y7, Kohara M8.
Author information
1
Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.
2
Joint Faculty of Veterinary Medicine, Kagoshima University, Korimoto, Kagoshima-city, Kagoshima 890-8580, Japan.
3
Department of Pathology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Influenza Virus Research Center, National Institute of Infectious Diseases, Gakuen, Musashimurayama-city, Tokyo 208-0011, Japan.
4
Toko Yakuhin Kogyo Co., Ltd., 20 Tsuji, Tateyama-machi, Toyama, 930-0211, Japan.
5
Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Health and Nutrition, Hachimandai, Tsukuba, Ibaraki, 305-0843, Japan.
6
Beacle, Inc., Yoshida-kawaracho, Sakyo-ku, Kyoto, 606-8305, Japan.
7
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shizukawa, Toon, Ehime, 791-0295, Japan.
8
Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan. Electronic address: [email protected].
Abstract
Hepatitis B virus (HBV) infection causes acute and chronic hepatitis, which is a major public health concern worldwide. Immunization methods incorporating hepatitis B surface-small (HBs-S) antigen and hepatitis B core antigen (HBc) have been proposed as candidate therapeutic vaccines, but the elimination of existing HBV infection remains a challenge. To enhance the efficacy of HBs and HBc vaccination, we investigated HBs-large (HBs-L) as an immunogen, and carboxyl vinyl polymer (CVP) as an excipient. HBs-S or HBs-L, in combination with HBc antigen, was administered subcutaneously (without CVP) or intranasally (with or without CVP) for the evaluation of immune response in the tree shrew, which is considered to be a suitable small animal model of HBV infection. Immunization with HBs-L antigen by either route induced a rapid IgG response. Intranasal immunization with HBs-S or HBs-L and HBc formulated with CVP strongly induced neutralizing antibody activity, IgA response, and HBc-specific expression of the interferon gamma-encoding gene. These data indicated the potential of HBs-L and HBc intranasal immunization with CVP, not only as a therapeutic vaccine, but also as a prophylactic vaccine candidate.