Neutralization of hepatitis B virus with vaccine-escape mutations by hepatitis B vaccine with large-HBs antigen

Ayaka Washizaki, Asako Murayama, Megumi Murata, Tomoko Kiyohara, Keigo Yato, Norie Yamada, Hussein Hassan Aly, Tomohisa Tanaka, Kohji Moriishi, Hironori Nishitsuji, Kunitada Shimotohno, Yasumasa Goh, Ken J. Ishii, Hiroshi Yotsuyanagi, Masamichi Muramatsu, Koji Ishii, Yoshimasa Takahashi, Ryosuke Suzuki, Hirofumi Akari () and Takanobu Kato ()
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Ayaka Washizaki: Kyoto University
Asako Murayama: National Institute of Infectious Diseases
Megumi Murata: Kyoto University
Tomoko Kiyohara: National Institute of Infectious Diseases
Keigo Yato: National Institute of Infectious Diseases
Norie Yamada: National Institute of Infectious Diseases
Hussein Hassan Aly: National Institute of Infectious Diseases
Tomohisa Tanaka: University of Yamanashi
Kohji Moriishi: University of Yamanashi
Hironori Nishitsuji: Fujita Health University School of Medicine
Kunitada Shimotohno: National Center for Global Health and Medicine
Yasumasa Goh: Research Laboratory, Beacle, Inc.
Ken J. Ishii: The University of Tokyo
Hiroshi Yotsuyanagi: The University of Tokyo
Masamichi Muramatsu: National Institute of Infectious Diseases
Koji Ishii: National Institute of Infectious Diseases
Yoshimasa Takahashi: National Institute of Infectious Diseases
Ryosuke Suzuki: National Institute of Infectious Diseases
Hirofumi Akari: Kyoto University
Takanobu Kato: National Institute of Infectious Diseases

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Although the current hepatitis B (HB) vaccine comprising small-HBs antigen (Ag) is potent and safe, attenuated prophylaxis against hepatitis B virus (HBV) with vaccine-escape mutations (VEMs) has been reported. We investigate an HB vaccine consisting of large-HBsAg that overcomes the shortcomings of the current HB vaccine. Yeast-derived large-HBsAg is immunized into rhesus macaques, and the neutralizing activities of the induced antibodies are compared with those of the current HB vaccine. Although the antibodies induced by the current HB vaccine cannot prevent HBV infection with VEMs, the large-HBsAg vaccine-induced antibodies neutralize those infections. The HBV genotypes that exhibited attenuated neutralization via these vaccines are different. Here, we show that the HB vaccine consisting of large-HBsAg is useful to compensate for the shortcomings of the current HB vaccine. The combined use of these HB vaccines may induce antibodies that can neutralize HBV strains with VEMs or multiple HBV genotypes.

Date: 2022
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DOI: 10.1038/s41467-022-32910-z

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