Equal Neutralization Potency of Antibodies Raised against Abrin Subunits

Abstract

Abrin and ricin are potent AB toxins, which are considered biological threats. To date, there are no approved treatments against abrin or ricin intoxications. Previously, we showed that the administration of polyclonal anti-abrin antibodies to mice that were intranasally exposed to abrin, even very late post-exposure, conferred an exceedingly high-level of protection, while following ricin intoxication, similar treatment with anti-ricin antibodies resulted in negligible survival rates. To probe this unexpected difference in protection ability, we first examined whether the efficient anti-abrin-induced protection was due to neutralization of the A-subunit responsible for the catalytic effect, or of the B-subunit, which enables binding/internalization, by evaluating the protection conferred by antibodies directed against one of the two subunits. To this end, we generated and immunized rabbits with chimeric toxins containing a single abrin subunit, AabrinBricin in which abrin A-subunit was linked to ricin B-subunit, and AricinBabrin in which ricin A-subunit is linked to abrin B-subunit. Here, we show that antibodies raised against either AabrinBricin or AricinBabrin conferred exceptionally high protection levels to mice following intranasal exposure to a a lethal dose of abrin, suggesting that the high level of protection conferred by anti-abrin antibodies is not related to the neutralization of a particular subunit.

Characterization of Lung Injury following Abrin Pulmonary Intoxication in Mice: Comparison to Ricin Poisoning

“…In sharp contrast, the administration of polyclonal anti-abrin antibodies to mice intranasally exposed to a lethal dose of abrin led to very high survival rates (~70-80%), even when the antibodies were applied as late as 72 h after intoxication [22]. This efficient protection by polyclonal anti-abrin antibodies could not be attributed to the neutralization of a single subunit because specific antibodies against the A or B subunits of abrin were equally effective in protecting mice against pulmonary intoxication with chimeric reciprocal toxins harboring one of the subunits of abrin and the other of ricin [24]. These observations indicated that the difference in the protection conferred by anti-abrin and anti-ricin antibodies against abrin and ricin intoxications, respectively, is not related to the difference in the quality of the two antibody preparations.…”

“…In contrast, the intranasal administration of polyclonal anti-abrin antibodies to mice even as late as 72 h postexposure to a lethal dose of abrin conferred exceedingly high-level protection [23]. Interestingly, the efficient protection by polyclonal anti-abrin antibodies cannot be attributed to the specific neutralization of a particular A or B subunit of the toxin, as antibodies raised against chimeric toxins of either an A abrin B ricin or A ricin B abrin structure conferred exceptionally high protection levels to mice following intranasal exposure to a lethal dose of abrin [24].…”

Neutralizing Monoclonal Antibody, mAb 10D8, Is an Effective Detoxicant against Abrin-a Both In Vitro and In Vivo

“…Many severe abrin poisoning cases and even death have been reported due to accidental and intentional abrin poisoning through ingestion, inhalation, and injection [ 14 ]. Currently, treatment for abrin poisoning is symptomatic, and there are no approved antidotes against abrin intoxications [ 15 ]. Neutralizing antibodies are known as a specific and effective strategy against biotoxin poisoning.…”