The Potential Use of Monoclonal Antibodies as Therapeutic Modalities in Neonatal Infection

Abstract

Group B streptococcal (GBS) and Escherichia coli infections are serious problems in human neonates. It is estimated that 11,000 cases of neonatal GBS disease occur per year in the US, resulting in 2600 deaths (1). In most series, GBS and E. coli account for approximately equal numbers of cases of neonatal sepsis and meningitis. Thus, over 20,000 cases of neonatal disease and 4000–5000 deaths occur per year owing to these two major bacterial pathogens. Approximately one-half of the survivors suffer significant sequelae. Thus, neonatal sepsis and meningitis are major health problems in this as well as in other countries throughout the world. Attempts have been made to improve methods for detecting and treating or preventing these infections, but to date these have not gained wide enough use to affect the problem significantly. The lack of opsonic antibody in human neonates is one major risk factor for the development of bacterial infection (2,3). In 1978, we (4) showed that the administration of fresh whole-blood transfusions, containing opsonic antibody, could be effective in decreasing mortality from GBS infection in human neonates. It was impossible to predict, however, whether blood donors would possess antibody to the bacterial strains causing infection. Furthermore, blood transfusion has significant risks, including transmission of infectious agents, such as hepatitis, cytomega- lovirus, and, more recently, the human immunodeficiency virus. Because of these problems, our group as well as others began to explore the possibility of using intravenous immunoglobulin (IVIG) in the therapy of experimental neonatal infection (5,6). These preparations had reasonable activity against less virulent GBS and E. coli strains, but almost no activity against more virulent strains, which produce or contain an excess of sialic acid in type-specific GBS or E. coli Kl antigens (7,8). Furthermore, significant lot-to-lot variation in antibody concentrations among the available IVIG preparations was detected (9). For these reasons, our group turned to the developing technology of making hybridoma antibodies as a way of producing more efficacious preparations for use in neonatal bacterial infection.

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