Comparison of functional activities between IgG1 and IgM class-switched human monoclonal antibodies reactive with group B streptococci or Escherichia coli K1.

The influence of valence and heavy chain on antibody activity was investigated using transfectoma-derived, class-switched IgG1 and IgM human monoclonal antibodies (MAbs) reactive with the bacterial pathogens Escherichia coli K1 and group B Streptococcus species. IgG-IgM pairs were compared in vitro for antigen binding and opsonic activities and in vivo for protective efficacy in neonatal rats. For the anti-E. coli pair, the IgM MAb was 1000-fold more potent in all assay formats. Importantly, the 50% protection dose (PD50) of the IgM MAb was 10-20 ng/rat, while 100-mu-g of the IgG MAb was only minimally protective. For the group B streptococcal MAbs, the IgM was 100- and 4500-fold more potent in binding and opsonization assays, respectively. However, while 20-mu-g of IgM protected neonatal rats, 100-mu-g of IgG MAb was partly protective. These experiments demonstrate the utility of recombinant DNA technology for creating a panel of antibodies that may aid in selecting potential immunotherapeutic candidates.