Toxins (Sep 2024)

A Monoclonal Antibody with a High Affinity for Ricin Isoforms D and E Provides Strong Protection against Ricin Poisoning

  • Loïs Lequesne,
  • Julie Dano,
  • Audrey Rouaix,
  • Camille Kropp,
  • Marc Plaisance,
  • Stéphanie Gelhaye,
  • Marie-Lou Lequesne,
  • Paloma Piquet,
  • Arnaud Avril,
  • François Becher,
  • Maria Lucia Orsini Delgado,
  • Stéphanie Simon

DOI
https://doi.org/10.3390/toxins16100412
Journal volume & issue
Vol. 16, no. 10
p. 412

Abstract

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Ricin is a highly potent toxin that has been used in various attempts at bioterrorism worldwide. Although a vaccine for preventing ricin poisoning (RiVax™) is in clinical development, there are currently no commercially available prophylaxis or treatments for ricin intoxication. Numerous studies have highlighted the potential of passive immunotherapy using anti-ricin monoclonal antibodies (mAbs) and have shown promising results in preclinical models. In this article, we describe the neutralizing and protective efficacy of a new generation of high-affinity anti-ricin mAbs, which bind and neutralize very efficiently both ricin isoforms D and E in vitro through cytotoxicity cell assays. In vivo, protection assay revealed that one of these mAbs (RicE5) conferred over 90% survival in a murine model challenged intranasally with a 5 LD50 of ricin and treated by intravenous administration of the mAbs 6 h post-intoxication. Notably, a 35% survival rate was observed even when treatment was administered 24 h post-exposure. Moreover, all surviving mice exhibited long-term immunity to high ricin doses. These findings offer promising results for the clinical development of a therapeutic candidate against ricin intoxication and may also pave the way for novel vaccination strategies against ricin or other toxins.

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