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

• Published in: Nature communications Vol. 13; no. 1; pp. 5207 - 12
• Main Authors: Washizaki, Ayaka, Murayama, Asako, Murata, Megumi, Kiyohara, Tomoko, Yato, Keigo, Yamada, Norie, Aly, Hussein Hassan, Tanaka, Tomohisa, Moriishi, Kohji, Nishitsuji, Hironori, Shimotohno, Kunitada, Goh, Yasumasa, Ishii, Ken J., Yotsuyanagi, Hiroshi, Muramatsu, Masamichi, Ishii, Koji, Takahashi, Yoshimasa, Suzuki, Ryosuke, Akari, Hirofumi, Kato, Takanobu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.09.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/109; 13/51; 14/1; 631/250/255/234/2513; 631/326/590; 631/326/596/1550; 692/4020/4021/234/2513/1549; 692/420/254; Antibodies; Antigens; Combined vaccines; Genotypes; Hepatitis; Hepatitis B; Hepatitis B surface antigen; Humanities and Social Sciences; Immunization; Morbidity; multidisciplinary; Mutation; Neutralization; Prophylaxis; Science; Science (multidisciplinary); Vaccines; Yeast
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-32910-z

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. The hepatitis B vaccine is recognised as the most effective approach in reducing hepatitis-B-related morbidity; vaccine-escape mutations are however capable of infecting vaccinated individuals. In this work, authors aim to establish a hepatitis B vaccine candidate, which they assess in rhesus macaques in terms of efficacy and safety.