A humanized monoclonal antibody targeting protein a promotes opsonophagocytosis of Staphylococcus aureus in human umbilical cord blood

Low and very-low-birth-weight (V/LBW) neonates are highly susceptible to bacterial sepsis and meningitis. Bacterial infections caused by Staphylococcus aureus can be particularly dangerous for neonates and can result in high mortality and long-term disabilities. Antibody-based strategies have been attempted to protect V/LBW neonates against staphylococcal disease. However, these efforts have so far been unsuccessful. Failures were attributed to the immaturity of the neonatal immune system but did not account for the anti-opsonic activity of Staphylococcal protein A (SpA). Here we show that monoclonal antibody 3F6, which blocks SpA activity, promotes complement-dependent cell-mediated phagocytosis of S. aureus in human umbilical cord blood. A substitution in the crystallizable fragment (Fc) region of 3F6 that enhances recruitment of complement component C1q further increases the phagocytic activity of cord blood. Our data demonstrate that the neonatal immune system possesses bactericidal activity that can be harnessed by antibodies that circumvent a key innate immune strategy of S. aureus.