title: Therapeutic potential of a fully human monoclonal antibody against influenza A virus M2 protein.
abstract: Influenza is one of the most prevalent viral diseases in humans. For some high-risk human populations, including the infant, the elderly, and the immunocompromised, who may not benefit from active immunization, passive immunotherapy with antibodies reactive with all influenza A strains may be an alternative. In this study, we characterized several fully human monoclonal antibodies (MAb) reactive with M2e, which were generated from transchromosomic mice engineered to produce fully human antibodies following immunization with a consensus-sequence M2e peptide. The MAbs showed strong binding to M2e peptide and to virus infected MDCK cells. One MAb recognizing the highly conserved N-terminal portion of consensus M2e displayed high binding to the majority of M2e variants from natural viral isolates, including highly pathogenic avian strains, which were recently reported to infect humans. Passive immunotherapy with this MAb in mice resulted in significant reduction in virus replication in the lung and protection from lethal infection when administered either prophylactically or therapeutically. These results suggest the potential of the anti-M2e human MAb with broad binding spectrum as a universal passive immunotherapeutic agent to infection by influenza A virus.
authors.affiliation: Kirin Pharma USA Inc, La Jolla, CA, USA.
authors.forename: Rongfang
authors.initials: R
authors.lastname: Wang
authors.forename: Aihua
authors.initials: A
authors.lastname: Song
authors.forename: James
authors.initials: J
authors.lastname: Levin
authors.forename: Dawna
authors.initials: D
authors.lastname: Dennis
authors.forename: Noelle J
authors.initials: NJ
authors.lastname: Zhang
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Lilia
authors.initials: L
authors.lastname: Koriazova
authors.forename: Lydia
authors.initials: L
authors.lastname: Madura
authors.forename: Laura
authors.initials: L
authors.lastname: Shapiro
authors.forename: Atsushi
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yoshida
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Mikayama
authors.forename: Ralph T
authors.initials: RT
authors.lastname: Kubo
authors.forename: Sally
authors.initials: S
authors.lastname: Sarawar
authors.forename: Hilde
authors.initials: H
authors.lastname: Cheroutre
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kato
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D000914:Antibodies, Viral / Q000008:administration & dosage; D000918:Antibody Specificity; D002460:Cell Line; D004285:Dogs; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D014763:Viral Matrix Proteins / Q000276:immunology*; D000086082:Viroporin Proteins
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins