Differential epitope recognition in the immunodominant staphylococcal antigen A of Staphylococcus aureus by mouse versus human IgG antibodies

Dennis G. A. M. Koedijk, Francisco Romero Pastrana, Hedzer Hoekstra, Sanne van den Berg, Jaap Willem Back, Carolien Kerstholt, Rianne C. Prins, Irma A. J. M. Bakker-Woudenberg, Jan Maarten van Dijl*, Girbe Buist

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

9 Citaten (Scopus)
223 Downloads (Pure)

Samenvatting

The immunodominant staphylococcal antigen A (IsaA) is a potential target for active or passive immunization against the important human pathogen Staphylococcus aureus. Consistent with this view, monoclonal antibodies against IsaA were previously shown to be protective against S. aureus infections in mouse models. Further, patients with the genetic blistering disease epidermolysis bullosa (EB) displayed high IsaA-specific IgG levels that could potentially be protective. Yet, mice actively immunized with IsaA were not protected against S. aureus infection. The present study was aimed at explaining these differences in IsaA-specific immune responses. By epitope mapping, we show that the protective human monoclonal antibody (humAb) 1D9 recognizes a conserved 62-residue N-terminal domain of IsaA. The same region of IsaA is recognized by IgGs in EB patient sera. Further, we show by immunofluorescence microscopy that this N-terminal IsaA domain is exposed on the S. aureus cell surface. In contrast to the humAb 1D9 and IgGs from EB patients, the non-protective IgGs from mice immunized with IsaA were shown to predominantly bind the C-terminal domain of IsaA. Altogether, these observations focus attention on the N-terminal region of IsaA as a potential target for future immunization against S. aureus.

Originele taal-2English
Artikelnummer8141
Aantal pagina's11
TijdschriftScientific Reports
Volume7
DOI's
StatusPublished - 15-aug-2017

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