Human Monoclonal Antibodies Broadly Neutralizing against Influenza B Virus

• Published in: PLoS pathogens Vol. 9; no. 2; p. e1003150
• Main Authors: Yasugi, Mayo, Kubota-Koketsu, Ritsuko, Yamashita, Akifumi, Kawashita, Norihito, Du, Anariwa, Sasaki, Tadahiro, Nishimura, Mitsuhiro, Misaki, Ryo, Kuhara, Motoki, Boonsathorn, Naphatsawan, Fujiyama, Kazuhito, Okuno, Yoshinobu, Nakaya, Takaaki, Ikuta, Kazuyoshi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.02.2013; Public Library of Science (PLoS)
• Subjects: Amino Acid Sequence; Amino acids; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - therapeutic use; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - therapeutic use; Antibodies, Viral - immunology; Antibodies, Viral - therapeutic use; Base Sequence; Binding sites; Biology; Dosage and administration; Drug therapy; Epitope Mapping; Experiments; Female; Genetic drift; Health risks; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Host-parasite relationships; Humans; Hybridomas; Influenza; Influenza B virus - genetics; Influenza B virus - immunology; Influenza, Human - drug therapy; Influenza, Human - immunology; Influenza, Human - prevention & control; Injections, Intraperitoneal; Lymphocytes; Mice; Mice, Inbred BALB C; Models, Molecular; Molecular Sequence Data; Monoclonal antibodies; Mutation; Neutralization Tests; Pandemics; Prevention; Proteins; Public health; Sequence Alignment; Sequence Analysis, DNA; Studies; Technological change; Treatment Outcome; Vaccines; Viral infections; Japan; Antibodies, Neutralizing; Amino Acid Sequence; Epitope Mapping; Humans; Injections, Intraperitoneal; Models, Molecular; Molecular Sequence Data; Neutralization Tests; Treatment Outcome; Antibodies, Monoclonal; Influenza B virus; Antibodies, Viral; Hemagglutinin Glycoproteins, Influenza Virus; Sequence Analysis, DNA; Sequence Alignment; Animals; Base Sequence; Hybridomas; Influenza, Human; Female; Mice; Mice, Inbred BALB C; Mutation
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1003150

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.