A natural human monoclonal antibody targeting Staphylococcus Protein A protects against Staphylococcus aureus bacteremia

PLoS One. 2018 Jan 24;13(1):e0190537. doi: 10.1371/journal.pone.0190537. eCollection 2018.

Abstract

Staphylococcus aureus can cause devastating and life-threatening infections. With the increase in multidrug resistant strains, novel therapies are needed. Limited success with active and passive immunization strategies have been attributed to S. aureus immune evasion. Here, we report on a monoclonal antibody, 514G3, that circumvents a key S. aureus evasion mechanism by targeting the cell wall moiety Protein A (SpA). SpA tightly binds most subclasses of immunoglobulins via their Fc region, neutralizing effector function. The organism can thus shield itself with a protective coat of serum antibodies and render humoral immunity ineffective. The present antibody reactivity was derived from an individual with natural anti-SpA antibody titers. The monoclonal antibody is of an IgG3 subclass, which differs critically from other immunoglobulin subclasses since its Fc is not bound by SpA. Moreover, it targets a unique epitope on SpA that allows it to bind in the presence of serum antibodies. Consequently, the antibody opsonizes S. aureus and maintains effector function to enable natural immune mediated clearance. The data presented here provide evidence that 514G3 antibody is able to successfully rescue mice from S. aureus mediated bacteremia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal* / immunology
  • Antibodies, Monoclonal* / therapeutic use
  • Bacteremia / immunology
  • Bacteremia / prevention & control
  • Humans
  • Immunoglobulin G
  • Mice
  • Staphylococcal Infections / immunology
  • Staphylococcal Infections / prevention & control*
  • Staphylococcal Protein A / immunology*

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin G
  • Staphylococcal Protein A

Grant support

XBiotech USA Inc. provided support in the form of salaries for authors A.K.V, G.A.K, J.L, K.M.S, R.A.B, T.K, H.R.M, A.R, Y.Z, R.L.M, M.C.C, J.S, S.S, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. No additional external funding was received for this study.