Characterization of the biological anti-staphylococcal functionality of hUK-66 IgG1, a humanized monoclonal antibody as substantial component for an immunotherapeutic approach.
Multi-antigen immunotherapy approaches against Staphylococcus aureus are expected to have the best chance of clinical success when used in combinatorial therapy, potentially incorporating opsonic killing of bacteria and toxin neutralization. We recently reported the development of a murine monoclonal antibody specific for the immunodominant staphylococcal antigen A (IsaA), which showed highly efficient staphylococcal killing in experimental infection models of S. aureus. If IsaA-specific antibodies are to be used as a component of combination therapy in humans, the binding specificity and biological activity of the humanized variant must be preserved. Here, we describe the functional characterization of a humanized monoclonal IgG1 variant designated, hUK-66. The humanized antibody showed comparable binding kinetics to those of its murine parent, and recognized the target antigen IsaA on the surface of clinically relevant S. aureus lineages. Furthermore, hUK-66 enhances the killing of S. aureus in whole blood (a physiological environment) samples from healthy subjects and patients prone to staphylococcal infections such as diabetes and dialysis patients, and patients with generalized artery occlusive disease indicating no interference with already present natural antibodies. Taken together, these data indicate that hUK-66 mediates bacterial killing even in high risk patients and thus, could play a role for immunotherapy strategies to combat severe S. aureus infections.
Institute for Molecular Infection Biology; University of Wuerzburg; Wuerzburg, Germany.
Babett
B
Oesterreich
Institute for Molecular Infection Biology; University of Wuerzburg; Wuerzburg, Germany.
Birgit
B
Lorenz
Institute for Molecular Infection Biology; University of Wuerzburg; Wuerzburg, Germany.
Tim
T
Schmitter
Institute for Cell Biology and Immunology; University of Stuttgart; Stuttgart, Germany.
Roland
R
Kontermann
Biaffin GmbH and Co. KG; Kassel, Germany.
Michael
M
Zenn
Biaffin GmbH and Co. KG; Kassel, Germany.
Bastian
B
Zimmermann
Institute for Molecular Infection Biology; University of Wuerzburg; Wuerzburg, Germany.
Markus
M
Haake
Department of General, Visceral, Vascular and Paediatric Surgery; University Clinic of Wuerzburg; Wuerzburg, Germany.
Udo
U
Lorenz
Institute for Molecular Infection Biology; University of Wuerzburg; Wuerzburg, Germany.
Knut
K
Ohlsen
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001770:Blood Bactericidal Activity; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D050296:Microbial Viability / Q000187:drug effects; D011485:Protein Binding; D013203:Staphylococcal Infections / Q000628:therapy*; D013211:Staphylococcus aureus / Q000276:immunology*
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000942:Antigens, Bacterial; D007074:Immunoglobulin G; C417673:IsaA antigen, staphylococcus
MRSA; Staphylococcus aureus; bacterial killing; fc-receptors; humanization; immunotherapeutics; immunotherapy; monoclonal antibodies; opsonophagocytosis; vaccinology