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

含有大 HBs 抗原的乙肝疫苗可中和因疫苗逃逸突变而产生的乙肝病毒

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作者: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

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.

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