A human monoclonal antibody targeting the conserved staphylococcal antigen IsaA protects mice against Staphylococcus aureus bacteremia
van den Berg, Sanne; Bonarius, Hendrik P J; van Kessel, Kok P M; Elsinga, Goffe S; Kooi, Neeltje; Westra, Hans; Bosma, Tjibbe; van der Kooi-Pol, Magdalena M; Koedijk, Danny G A M; Groen, Herman; van Dijl, Jan Maarten; Buist, Girbe; Bakker-Woudenberg, Irma A J M; van Kessel, CPM
(2015) International Journal of Medical Microbiology, volume 305, issue 1, pp. 55 - 64
(Article)
Abstract
Due to substantial therapy failure and the emergence of antibiotic-resistant Staphylococcus aureus strains, alternatives for antibiotic treatment of S. aureus infections are urgently needed. Passive immunization using S. aureus-specific monoclonal antibodies (mAb) could be such an alternative to prevent and treat severe S. aureus infections. The invariantly expressed immunodominant staphylococcal
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antigen A (IsaA) is a promising target for passive immunization. Here we report the development of the human anti-IsaA IgG1 mAb 1D9, which was shown to bind to all 26 S. aureus isolates tested. These included both methicillin-susceptible and methicillin-resistant S. aureus (MSSA and MRSA, respectively). Immune complexes consisting of IsaA and 1D9 stimulated human as well as murine neutrophils to generate an oxidative burst. In a murine bacteremia model, the prophylactic treatment with a single dose of 5 mg/kg 1D9 improved the survival of mice challenged with S. aureus isolate P (MSSA) significantly, while therapeutic treatment with the same dose did not influence animal survival. Neither prophylactic nor therapeutic treatment with 5 mg/kg 1D9 resulted in improved survival of mice with S. aureus USA300 (MRSA) bacteremia. Importantly, our studies show that healthy S. aureus carriers elicit an immune response which is sufficient to generate protective mAbs against invariant staphylococcal surface antigens. Human mAb 1D9, possibly conjugated to for example another antibody, antibiotics, cytokines or chemokines, may be valuable to fight S. aureus infections in patients.
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Keywords: Animals, Antibodies, Bacterial, Antibodies, Monoclonal, Antigens, Bacterial, Bacteremia, Disease Models, Animal, Female, Immunization, Passive, Mice, Inbred BALB C, Staphylococcal Infections, Survival Analysis, Treatment Outcome, Virulence Factors, Journal Article, Research Support, Non-U.S. Gov't
ISSN: 1438-4221
Publisher: Elsevier
Note: Copyright © 2014 Elsevier GmbH. All rights reserved.
(Peer reviewed)