Ricin Antibodies’ Neutralizing Capacity against Different Ricin Isoforms and Cultivars

Delgado, María Lucía Orsini; Avril, Arnaud; Prigent, Julie; Dano, Julie; Rouaix, Audrey; Worbs, Sylvia; Dorner, Brigitte G.; Rougeaux, Clémence; Bécher, François; Fenaille, François; Livet, Sandrine; Volland, Hervé; Tournier, Jean‐Nicolas; Simon, Stéphanie

doi:10.3390/toxins13020100

Cited by 16 publications

(8 citation statements)

References 52 publications

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“…A recent study evidenced the effectiveness of the synergistic effect when combining RB34 and 43RCA-G1 antibodies. This synergistic effect was confirmed in vivo in a mouse model of intranasal intoxication with ricin D and E [ 103 ]. The combination of RB34 and 43RCA-G1 had the best neutralizing capacity.…”

Section: Current Therapeutic Antibodiesmentioning

confidence: 84%

Medical Countermeasures against Ricin Intoxication

Rasetti-Escargueil

Avril²

2023

Toxins

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Ricin toxin is a disulfide-linked glycoprotein (AB toxin) comprising one enzymatic A chain (RTA) and one cell-binding B chain (RTB) contained in the castor bean, a Ricinus species. Ricin inhibits peptide chain elongation via disruption of the binding between elongation factors and ribosomes, resulting in apoptosis, inflammation, oxidative stress, and DNA damage, in addition to the classically known rRNA damage. Ricin has been used in traditional medicine throughout the world since prehistoric times. Because ricin toxin is highly toxic and can be readily extracted from beans, it could be used as a bioweapon (CDC B-list). Due to its extreme lethality and potential use as a biological weapon, ricin toxin remains a global public health concern requiring specific countermeasures. Currently, no specific treatment for ricin intoxication is available. This review focuses on the drugs under development. In particular, some examples are reviewed to demonstrate the proof of concept of antibody-based therapy. Chemical inhibitors, small proteins, and vaccines can serve as alternatives to antibodies or may be used in combination with antibodies.

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Section: Current Therapeutic Antibodiesmentioning

confidence: 84%

Medical Countermeasures against Ricin Intoxication

Rasetti-Escargueil

Avril²

2023

Toxins

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“…This pipeline was successfully used for the development of antibodies against different biological agent such as botulinum neurotoxins [ 18 ], ricin [ 19 , 20 , 21 ], haemorrhagic fevers [ 22 , 23 ] or anthrax toxins [ 12 , 24 ] and is currently used for the development of anti-orthopoxviruses antibodies.…”

Section: Resultsmentioning

confidence: 99%

“…(mutation of amino acids in both FR and in the complementary determining regions -CDR-) for the humanization of the antibodies that we developed. This pipeline was successfully used for the development of antibodies against different biological agent such as botulinum neurotoxins [18], ricin [19][20][21], haemorrhagic fevers [22,23] or anthrax toxins [12,24] and is currently used for the development of antiorthopoxviruses antibodies.…”

Section: Pipeline Used For the Research And Development Of Human-like...mentioning

confidence: 99%

“…This resulting Fab library was then panned by the phage-display technology against PA83 antigen. Five rounds of panning were realized, with increasing This pipeline was successfully used for the development of antibodies against different biological agent such as botulinum neurotoxins [18], ricin [19][20][21], haemorrhagic fevers [22,23] or anthrax toxins [12,24] and is currently used for the development of antiorthopoxviruses antibodies.…”

Section: Development Of An Anti-pa Antibodymentioning

confidence: 99%

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Antibodies against Anthrax Toxins: A Long Way from Benchlab to the Bedside

Avril¹,

Tournier

Paucod³

et al. 2022

Toxins

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Anthrax is an acute disease caused by the bacterium Bacillus anthracis, and is a potential biowarfare/bioterrorist agent. Its pulmonary form, caused by inhalation of the spores, is highly lethal and is mainly related to injury caused by the toxins secretion. Antibodies neutralizing the toxins of B. anthracis are regarded as promising therapeutic drugs, and two are already approved by the Federal Drug Administration. We developed a recombinant human-like humanized antibody, 35PA83 6.20, that binds the protective antigen and that neutralized anthrax toxins in-vivo in White New Zealand rabbits infected with the lethal 9602 strain by intranasal route. Considering these promising results, the preclinical and clinical phase one development was funded and a program was started. Unfortunately, after 5 years, the preclinical development was cancelled due to industrial and scientific issues. This shutdown underlined the difficulty particularly, but not only, for an academic laboratory to proceed to clinical development, despite the drug candidate being promising. Here, we review our strategy and some preliminary results, and we discuss the issues that led to the no-go decision of the pre-clinical development of 35PA83 6.20 mAb. Our review provides general information to the laboratories planning a (pre-)clinical development.

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“…Upstream of clinical development, an example of antibody characterization for therapeutic applications is given in the article of Delgado et al [ 2 ]. The article describes the development and characterization of therapeutic antibodies directed against ricin (a toxin easy to purify from the plant Ricinus communis and potentially used as a biowarfare agent), using in vitro and in vivo (mouse model) approaches.…”

mentioning

confidence: 99%