Plectasin is a 4.4-kDa
antimicrobial peptide with the potential to be a treatment of
infections caused by gram-positive bacteria. Since
plectasin is a large molecule compared to conventional
antibiotics, the development of antidrug
antibodies (ADAs) could be anticipated. The immunogenic properties of
plectasin were assessed through immunization studies. In mice treated for 5 days with one to two daily subcutaneous doses of
plectasin, no antibody response was observed. If the animals were immunized again, after a rest period, low levels of
antibodies developed in approximately half the animals. Additionally, mice were immunized with
plectasin in Freund's incomplete adjuvant (FIA). Ninety-two percent of these mice developed ADAs after repeated immunizations, with two-thirds having high levels of
antibodies. An
agar diffusion bioassay showed that sera from animals immunized with
plectasin did not inhibit the efficacy of the
drug, while hyperimmune sera from animals in which an immune response was provoked by immunization with
plectasin in FIA reduced the efficacy of
plectasin at the lowest concentration tested. Studies in the murine
peritonitis model showed an excellent efficacy of
plectasin for the treatment of
Streptococcus pneumoniae infections both in naïve animals and in animals with ADAs. No difference in bacterial counts was seen when the animals were treated with
plectasin at 2.5 mg/kg of
body weight, a dose below the expected therapeutic level. When animals were treated with
plectasin at 0.625 mg/kg, the effect was reduced but not neutralized in animals with high levels of ADAs. No animals showed signs of
hypersensitivity or
injection site reactions toward
plectasin, and the half-life of the compound did not vary between animals with and without
antibodies.