A Humanized Monoclonal Antibody Cocktail to Prevent Pulmonary Ricin Intoxication

Toxins (Basel). 2020 Mar 29;12(4):215. doi: 10.3390/toxins12040215.

Abstract

PB10 IgG1, a monoclonal antibody (MAb) directed against an immunodominant epitope on the enzymatic subunit (RTA) of ricin toxin (RT), has been shown to passively protect mice and non-human primates from an aerosolized lethal-dose RT challenge. However, it was recently demonstrated that the therapeutic efficacy of PB10 IgG1 is significantly improved when co-administered with a second MAb, SylH3, targeting RT's binding subunit (RTB). Here we report that the PB10/SylH3 cocktail is also superior to PB10 alone when used as a pre-exposure prophylactic (PrEP) in a mouse model of intranasal RT challenge. The benefit of the PB10/SylH3 cocktail prompted us to engineer a humanized IgG1 version of SylH3 (huSylH3). The huPB10/huSylH3 cocktail proved highly efficacious in the mouse model, thereby opening the door to future testing in non-human primates.

Keywords: antibody; biodefense; lung; prophylactic; toxin.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Inhalation
  • Animals
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antibodies, Neutralizing / administration & dosage
  • Antibodies, Neutralizing / pharmacology*
  • Antidotes / administration & dosage
  • Antidotes / pharmacology*
  • Chlorocebus aethiops
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Female
  • Lung Diseases / chemically induced
  • Lung Diseases / prevention & control*
  • Mice, Inbred BALB C
  • Pre-Exposure Prophylaxis
  • Ricin / antagonists & inhibitors*
  • Ricin / immunology
  • Vero Cells

Substances

  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing
  • Antidotes
  • Ricin