Open AccessGeneration and Improvement of Effector Function of a Novel Broadly Reactive and Protective Monoclonal Antibody against Pneumococcal Surface Protein A of Streptococcus pneumoniae
Author(s) -
Sascha A. Kristian,
Takayuki Ota,
Sarah S. Bubeck,
Rebecca Cho,
Brian Groff,
Tsuguo Kubota,
Giuseppe Destito,
John Laudenslager,
Lilia Koriazova,
Tomoyuki Tahara,
Yutaka Kanda
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0154616
Subject(s) - streptococcus pneumoniae , monoclonal antibody , effector , pneumococcal pneumonia , pneumococcal infections , microbiology and biotechnology , biology , antibody , pneumonia , immunology , sepsis , antibiotics , medicine
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.