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Immunoneutralization of Abrin

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Biological Toxins and Bioterrorism

Part of the book series: Toxinology ((TOXI))

Abstract

Abrin is a type II ribosome-inactivating protein obtained from the mature seeds of a subtropical plant named Abrus precatorius. It is a glycoprotein which arrests protein synthesis in eukaryotes by inactivating ribosomes irreversibly. The heterodimeric protein comprises of the toxic subunit, the A chain which is disulfide bonded to the B chain, a galactose-specific lectin, which helps in binding and trafficking of the toxin in cells. A single molecule of the abrin A chain which reaches the cytosol is sufficient to kill the cell. Owing to its extreme toxicity and ease of purification and dissemination, abrin is considered as a dreaded bioterror agent. In spite of several reports on abrin poisoning, there is no effective antidote or vaccine available against the lethal toxin. An active site mutant of the abrin A chain has been proposed as a potential vaccine candidate against abrin intoxication, though it might not be useful for public at large. However, passive administration of antibodies has served as the primary mode of therapy against a large number of toxins. To date, the monoclonal antibody D6F10 is the only known neutralizing antibody reported against abrin. The antibody can rescue cells as well as mice challenged with lethal doses of the toxin. A recent study has demonstrated that the epitope corresponding to the antibody is present in close proximity to the active site of abrin A chain and the antibody can neutralize abrin-mediated cytotoxicity intracellularly. Humanization of the antibody and a detailed understanding of the trafficking of the abrin-antibody complex are required for its development as therapy, pre- and post-abrin exposure.

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Abbreviations

ABA:

Abrin A chain

APA:

Abrus precatorius agglutinin

BAT3:

HLA-B-associated transcript3

DEAE:

Diethylamino ethyl cellulose

EF-2:

Elongation factor 2

ER:

Endoplasmic reticulum

ERAD:

ER-associated degradation

ICP:

Intracranial pressure

Ig:

Immunoglobulin

ITs:

Immunotoxins

JNK:

cJun N-terminal kinase

kDa:

kilo Dalton

LD50:

50 % lethal dose

mAb:

Monoclonal antibody

MAPK:

Mitogen activated protein kinase

MKK4:

MAPK kinase 4

PCR:

Polymerase chain reaction

PDB:

Protein data bank

PDI:

Protein disulfide isomerase

RCA:

Ricinus communis agglutinin

RIPs:

Ribosome-inactivating proteins

rRNA:

Ribosomal ribonucleic acid

RTA:

Ricin A chain

SAPK:

Stress-activated protein kinase

SEK1:

Stress signaling kinase1

TNF:

Tumor necrosis factor

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Author information

Authors and Affiliations

  1. Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka, India

    Shradha Bagaria & Anjali A. Karande

Authors
  1. Shradha Bagaria
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  2. Anjali A. Karande
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Corresponding author

Correspondence to Anjali A. Karande .

Editor information

Editors and Affiliations

  1. Venom and Toxin Research Programme, Department of Anatomy, Yong Loo Lin School of Medicine National University of Singapore, Singapore, Singapore

    P. Gopalakrishnakone

  2. Medical Toxicology Research Centre Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Mahdi Balali-Mood

  3. Data and Technology Innovation, Australian Institute of Marine Science, Townsville, QLD, Australia

    Lyndon Llewellyn

  4. Botulinum Research Center, Institute of Advanced Sciences, Dartmouth, MA, USA

    Bal Ram Singh

  5. Prime Bio, Inc., Dartmouth, MA, USA

    Bal Ram Singh

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Bagaria, S., Karande, A.A. (2015). Immunoneutralization of Abrin. In: Gopalakrishnakone, P., Balali-Mood, M., Llewellyn, L., Singh, B.R. (eds) Biological Toxins and Bioterrorism. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5869-8_9

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