Human Monoclonal Antibodies Broadly Neutralizing against Influenza B Virus

PLoS Pathogens

Ryo Misaki¹  Mitsuhiro Nishimura²  Mayo Yasugi³  Takaaki Nakaya³  Motoki Kuhara³  Norihito Kawashita³  Kazuhito Fujiyama³  Ritsuko Kubota-Koketsu⁴  Tadahiro Sasaki⁵  Akifumi Yamashita⁶  Naphatsawan Boonsathorn⁶  Anariwa Du⁶  Kazuyoshi Ikuta⁶  Yoshinobu Okuno⁶ 

[1] Department of Environmental Pharmacometrics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan;Department of Genome Informatics, RIMD, Osaka University, Suita, Osaka, Japan;Department of Virology, Research Institute for Microbial Diseases (RIMD), Osaka University, Suita, Osaka, Japan;Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan;Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa, Japan;The Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo, Japan

关键词: Influenza B virus;    Sequence databases;    Influenza A virus;    Cell fusion;    Influenza;    Dengue virus;    Hybridomas;    Infectious disease control;   

DOI  :  10.1371/journal.ppat.1003150

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Influenza virus has the ability to evade host immune surveillance through rapid viral genetic drift and reassortment; therefore, it remains a continuous public health threat. The development of vaccines producing broadly reactive antibodies, as well as therapeutic strategies using human neutralizing monoclonal antibodies (HuMAbs) with global reactivity, has been gathering great interest recently. Here, three hybridoma clones producing HuMAbs against influenza B virus, designated 5A7, 3A2 and 10C4, were prepared using peripheral lymphocytes from vaccinated volunteers, and were investigated for broad cross-reactive neutralizing activity. Of these HuMAbs, 3A2 and 10C4, which recognize the readily mutable 190-helix region near the receptor binding site in the hemagglutinin (HA) protein, react only with the Yamagata lineage of influenza B virus. By contrast, HuMAb 5A7 broadly neutralizes influenza B strains that were isolated from 1985 to 2006, belonging to both Yamagata and Victoria lineages. Epitope mapping revealed that 5A7 recognizes 316G, 318C and 321W near the C terminal of HA1, a highly conserved region in influenza B virus. Indeed, no mutations in the amino acid residues of the epitope region were induced, even after the virus was passaged ten times in the presence of HuMAb 5A7. Moreover, 5A7 showed significant therapeutic efficacy in mice, even when it was administered 72 hours post-infection. These results indicate that 5A7 is a promising candidate for developing therapeutics, and provide insight for the development of a universal vaccine against influenza B virus.

【 授权许可】

CC BY