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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.

SUBMITTER: Kristian SA 

PROVIDER: S-EPMC4865217 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Generation and Improvement of Effector Function of a Novel Broadly Reactive and Protective Monoclonal Antibody against Pneumococcal Surface Protein A of Streptococcus pneumoniae.

Kristian Sascha A SA   Ota Takayuki T   Bubeck Sarah S SS   Cho Rebecca R   Groff Brian C BC   Kubota Tsuguo T   Destito Giuseppe G   Martin Cécile C   Laudenslager John J   Koriazova Lilia L   Tahara Tomoyuki T   Kanda Yutaka Y  

PloS one 20160512 5


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  ...[more]

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