Pharmacokinetic and Pharmacodynamic Analysis of a Human Immunoglobulin M Monoclonal Antibody in Neonatal Macaca fascicularis

Abstract

ABSTRACT. We have developed a human Neonatal infections caused by GBS and Escherichia coli K1still have unacceptably high mortality and morbidity rates (6). To supplement current antibiotic therapy, we have developed human MAb with immunotherapeutic potential. Human IgM MAb produced against the group carbohydrate of GBS or the E. coli K1 capsule were found to protect against lethal infections in animal models (7,8). Although administration of human MAb does not have obvious risks, it is still necessary to insure the safety of individual MAb and the methods used for their preparation. Moreover, because these MAb are intended for treatment of infections in neonates, exploring their safety is of paramount importance.Before initiating formal preclinical safety and PK studies, we performed a preliminary study using two nonhuman primate neonates. The data indicate the GBS MAb is safe without apparent toxicity for the major organ systems or impairment of bone marrow function. Further, in neonatal monkeys the IgM MAb has a half-life of approximately 2.5 d and maintains commensurate opsonic activity.

Bacterial carbohydrates in neonatal sepsis: targets for immunotherapy

“…These data show that the GBS mAb was as protective as polyclonal sera containing IgG antibodies against each of the four capsule polysaccharides. A highly defined A preclinical neonatal monkey study was conducted with IgM GBS mAb to provide information useful for predicting the safety and pharmacokinetic properties of this mAb [12]. Two neonatal Macacafascicularis monkeys less than 7 days old were infused with the mAb at either 17.8 or 230 mg/kg.…”