Pharmacokinetic and pharmacodynamic analysis of a human immunoglobulin M monoclonal antibody in neonatal Macaca fascicularis.

We have developed a human MAb that opsonizes group B streptococci, the major cause of gram-positive bacterial sepsis in newborns. It is an IgM class human MAb that possess unique protective activity against experimental infections caused by the predominant group B capsule serotypes III and I. Preliminary preclinical studies with the IgM human MAb were designed to provide initial information useful for predicting its safety and pharmacokinetic properties. Two neonatal Macaca fascicularis monkeys were infused with the human MAb at either 17.8 or 230 mg/kg. Safety was evaluated by visually monitoring postinfusion clinical status and by standard clinical chemistry analyses and quantitative hematology on blood samples collected for 30 d. The serum antibody levels were determined by ELISA and antibody functional activity in serum samples by opsonophagocytic assays. The IgM human MAb appeared safe (normal laboratory values and clinical status) with a half-life of 2.5 d, a period compatible with the 5-d half-life reported for human IgM in adult serum. In addition, the human MAb retained functional opsonic activity for at least 30 d. Human MAb may offer a safe alternative for treating severe bacterial infections.