title: Generation and Improvement of Effector Function of a Novel Broadly Reactive and Protective Monoclonal Antibody against Pneumococcal Surface Protein A of Streptococcus pneumoniae.
abstract: A proof-of-concept study evaluating the potential of Streptococcus pneumoniae Pneumococcal Surface Protein A (PspA) as a passive immunization target was conducted. We describe the generation and isolation of several broadly reactive mouse anti-PspA monoclonal antibodies (mAbs). MAb 140H1 displayed (i) 98% strain coverage, (ii) activity in complement deposition and opsonophagocytic killing (OPK) assays, which are thought to predict the in vivo efficacy of anti-pneumococcal mAbs, (iii) efficacy in mouse sepsis models both alone and in combination with standard-of-care antibiotics, and (iv) therapeutic activity in a mouse pneumonia model. Moreover, we demonstrate that antibody engineering can significantly enhance anti-PspA mAb effector function. We believe that PspA has promising potential as a target for the therapy of invasive pneumococcal disease by mAbs, which could be used alone or in conjunction with standard-of-care antibiotics.
authors.affiliation: Kyowa Kirin Pharmaceutical Research, Inc., 9420 Athena Circle, La Jolla, CA 92037, United States of America.
authors.forename: Sascha A
authors.initials: SA
authors.lastname: Kristian
authors.affiliation: Kyowa Hakko Kirin Co., Ltd., R&D Division, 1-6-1, Ōtemachi, Chiyoda-ku, Tokyo 100-8185, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ota
authors.affiliation: Kyowa Kirin Pharmaceutical Research, Inc., 9420 Athena Circle, La Jolla, CA 92037, United States of America.
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Bubeck
authors.affiliation: Kyowa Kirin Pharmaceutical Research, Inc., 9420 Athena Circle, La Jolla, CA 92037, United States of America.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Cho
authors.affiliation: Kyowa Kirin Pharmaceutical Research, Inc., 9420 Athena Circle, La Jolla, CA 92037, United States of America.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Groff
authors.affiliation: Kyowa Hakko Kirin Co., Ltd., R&D Division, 1-6-1, Ōtemachi, Chiyoda-ku, Tokyo 100-8185, Japan.
authors.forename: Tsuguo
authors.initials: T
authors.lastname: Kubota
authors.affiliation: Kyowa Kirin Pharmaceutical Research, Inc., 9420 Athena Circle, La Jolla, CA 92037, United States of America.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Destito
authors.affiliation: Kyowa Kirin Pharmaceutical Research, Inc., 9420 Athena Circle, La Jolla, CA 92037, United States of America.
authors.forename: Cécile
authors.initials: C
authors.lastname: Martin
authors.affiliation: Kyowa Kirin Pharmaceutical Research, Inc., 9420 Athena Circle, La Jolla, CA 92037, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Laudenslager
authors.affiliation: Kyowa Kirin Pharmaceutical Research, Inc., 9420 Athena Circle, La Jolla, CA 92037, United States of America.
authors.forename: Lilia
authors.initials: L
authors.lastname: Koriazova
authors.affiliation: Kyowa Hakko Kirin Co., Ltd., R&D Division, 1-6-1, Ōtemachi, Chiyoda-ku, Tokyo 100-8185, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tahara
authors.affiliation: Kyowa Hakko Kirin Co., Ltd., R&D Division, 1-6-1, Ōtemachi, Chiyoda-ku, Tokyo 100-8185, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kanda
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000276:immunology*; D003176:Complement C3 / Q000378:metabolism; D004195:Disease Models, Animal; D018604:Epitope Mapping; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008171:Lung Diseases / Q000276:immunology / Q000382:microbiology; D008807:Mice, Inbred BALB C; D009895:Opsonin Proteins / Q000378:metabolism; D010586:Phagocytes / Q000378:metabolism; D010587:Phagocytosis; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D011485:Protein Binding; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D003176:Complement C3; D007074:Immunoglobulin G; D009895:Opsonin Proteins; C051592:pneumococcal surface protein A