Protection against inhalation toxicity of ricin and abrin by immunisation

Abstract

<jats:p> 1 Abrin and ricin are highly toxic plant proteins which are very similar in structure and function and inhibit protein synthesis in eukaryotes. </jats:p><jats:p> 2 Rats have been immunised against either toxin using formaldehyde-toxoids by three subcutaneous injections at intervals of 3 weeks. For abrin, serum titres in 14 out of 15 rats were raised to between 1 : 12800 and 1 : 51200 after two injections, 6 weeks from the start of the experiment. Titres of between 1 : 256 and 1 : 1024 were also measured in lung washes after challenge with active abrin toxin. </jats:p><jats:p> 3 The three major antibody classes, IgG, IgM and IgA were present in the immune sera but IgG and IgA only were detected in lung washes. The proportion of IgA to IgG was higher in the lung fluid than in sera. Rats immunised by abrin toxoid were protected against 5 LCt<jats:sub>50</jats:sub>'s of abrin by inhalation but others exposed to ricin were not. </jats:p><jats:p> 4 For ricin, serum titres ranged from 1 : 800 to 1 : 25600 after two injections and after a third injection the titre range was the same but population samples were weighted towards the higher titres. All rats immunised with ricin toxoid survived the challenge of 5 LCt<jats:sub>50</jats:sub>'s of ricin toxin by inhalation over the observation period of 28 days post-challenge. </jats:p><jats:p> 5 Representative immunised rats (abrin toxoid) were taken at various times post-exposure, humanely killed and tissues were examined for pathological changes. It was concluded that an apparently severe lung lesion occurred at a later time than in non-immunised, toxin challenged rats. This damage was not lethal over the experimental observation periods. </jats:p><jats:p> 6 Immunisation by the sub-cutaneous route therefore protects against lethality from challenge by inhalation of ricin or abrin toxins but does not prevent significant lung damage. </jats:p>

RiVax, a recombinant ricin subunit vaccine, protects mice against ricin delivered by gavage or aerosol

“…vaccines protect mice from lethal ricin challenges. However, when aerosolized ricin was delivered to the vaccinated mice they still suffered significant lung damage [ 7,28 ]. Intranasal or intratracheal instillation of the toxoid induced good systemic immunity but failed to activate an adequate local response to protect the lungs.…”

Ribosome Depurination Is Not Sufficient for Ricin-Mediated Cell Death in Saccharomyces cerevisiae

“…Inhalation of small amounts of ricin aerosol can rapidly and irreversibly damage cells of the respiratory tract, leading to severe pulmonary incapacitation or death (3,12). Currently, there is no approved antidote, vaccine, or other specific medical treatment option for ricin exposure.…”

A novel recombinant vaccine protecting mice against abrin intoxication

“…Compared with A chain subunit, conventional toxoid preparation via protein denaturation has significant shortfalls that can lead to inadequate vaccine potency and poor quality control. 4,5,24 ATB is a galactose-specific lectin and can bind to cell surface glycosylated receptors and promote the entry of the ATA into the cytosol, which means that ATB is essential for the toxicity of AT. Meanwhile, previous studies also have demonstrated that B chain of toxins can exhibit both antigenic and adjuvant activity.…”

“…These characteristics make AT a choice for a suitable assassination weapon or a biological warfare agent . 3 Toxin poisoning usually can be prevented by vaccination with toxoid, 4,5 or by passive administration with antibodies in experimental animals. 2,6 Both procedures are effective in the prophylaxis or therapy of toxin poisoning in mice.…”