Characterization and Protective Activity of Monoclonal Antibodies Directed against Streptococcus suis Serotype 2 Capsular Polysaccharide Obtained Using a Glycoconjugate.

Guillaume Goyette-Desjardins,Jean-Philippe Auger,Mariela Segura,Marcelo Gottschalk,Sonia Lacouture,René Roy

doi:10.3390/pathogens8030139

Abstract

Streptococcus suis serotype 2 is an encapsulated bacterium and an important swine pathogen. Opsonizing antibody responses targeting capsular polysaccharides (CPSs) are protective against extracellular pathogens. To elucidate the protective activity of monoclonal antibodies (mAbs) directed against S. suis serotype 2 CPS, mice were immunized with a serotype 2 CPS-glycoconjugate and three hybridomas were isolated; of which, two were murine IgMs and the other a murine IgG1. Whereas the IgMs (mAbs 9E7 and 13C8) showed different reactivity levels with S. suis serotypes 1, 1/2, 2 and 14, the IgG1 (mAb 16H11) was shown to be serotype 2-specific. All mAbs targeted the sialylated chain of the CPSs. Using an opsonophagocytosis assay, the IgMs were opsonizing towards the S. suis serotypes to which they cross-react, while the IgG1 failed to induce bacterial elimination. In a model of mouse passive immunization followed by a lethal challenge with S. suis serotype 2, the IgG1 and IgM cross-reacting only with serotype 14 (mAb 13C8) failed to protect, while the IgM cross-reacting with serotypes 1, 1/2, and 14 (mAb 9E7) was shown to be protective by limiting bacteremia. These new mAbs show promise as new S. suis diagnostic tools, as well as potential for therapeutic applications.

Highlights

Streptococcus suis is an encapsulated Gram-positive bacterium and one of the most important bacterial pathogens in the porcine industry, resulting in important economic losses [1]
The screening steps against S. suis type 2 capsular polysaccharides (CPSs) of monoclonal antibodies (mAbs) production by ELISA led to the selection of 3 positive clones: 9E7 (IgM), 13C8 (IgM), and 16H11 (IgG1) out of 700 clones tested
It had originally been reported to be an IgG2b, mAb Z3 was found later to be of the IgM isotype (Table S1); this discrepancy could be explained by the low specificity of the commercial reagents that were available at the time of the study by Charland et al [22]

Summary

Introduction

Streptococcus suis is an encapsulated Gram-positive bacterium and one of the most important bacterial pathogens in the porcine industry, resulting in important economic losses [1]. The capsular polysaccharide (CPS) antigenic diversity has allowed the classification of S. suis in 35 serotypes. S. suis serotype 2 is considered the most virulent, being the serotype most frequently isolated from clinical samples and associated with disease in swine in most countries [2]. 2, is an important emerging zoonotic agent for people in close contact with pigs or pig-derived products [2]. Of the various manifestations of the disease, septicemia and meningitis are by far the most remarkable, but other pathologies have been observed [1]. Research has been ongoing for decades in the hope of developing an efficient commercial vaccine to protect post-weaning pigs against

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