Establishment of monoclonal antibodies broadly neutralize infection of hepatitis B virus

Autor: He Zhang, Yumi Itoh, Tatsuya Suzuki, Kan‐ichiro Ihara, Tomohisa Tanaka, Saori Haga, Hajime Enatsu, Maho Yumiya, Mari Kimura, Akira Takada, Daiki Itoh, Yuri Shibazaki, Shuto Nakao, Sachiyo Yoshio, Kei Miyakawa, Yuki Miyamoto, Hanae Sasaki, Tadahiro Kajita, Masaya Sugiyama, Masashi Mizokami, Taro Tachibana, Akihide Ryo, Kohji Moriishi, Eiji Miyoshi, Tatsuya Kanto, Toru Okamoto, Yoshiharu Matsuura
Rok vydání: 2022
Předmět:
Zdroj: Microbiology and immunologyREFERENCES. 66(4)
ISSN: 1348-0421
Popis: Antibodies against hepatitis B virus S protein can protect against hepatitis B virus (HBV) infection. Therefore, hepatitis B immunoglobulin (HBIG), which contains HBsAb, is used clinically as a therapy for HBV infection. In this study, a series of monoclonal antibodies that recognize multiple HBV genotypes was obtained. All the antibodies recognized conformational epitopes of S protein, but not linear epitopes. Several antibodies neutralized HBV infection and exhibited strong affinities and neutralizing activities. Antigenic epitope analysis demonstrated that they recognized residue Ile152 of S protein, which is localized outside the "a" determinant. Ile152 is highly conserved, and a mutation in this residue resulted in reduced expression of large hepatitis B surface proteins (L protein), suggesting that the amino acid at this position is involved in the expression of L protein. In addition, the antibodies neutralized the infection of hepatitis D virus possessing a Gly145 mutation to Arg in S protein, which is a well-known escape mutation against HBIG treatment. Using mouse monoclonal antibodies, a humanized antibody possessing affinities and neutralizing activities similar to those of the original mouse antibody was successfully established. The antibodies generated in this study may have the potential for use in alternative antibody therapies for HBV infection.
Databáze: OpenAIRE