The B-subunit of ricin toxin is involved in eliciting protective antibodies (106.18)

Abstract

Abstract The ricin toxin B subunit (RTB) is a galactose-specific lectin that promotes attachment and entry of the ricin enzymatic subunit (RTA) into host cells. RTB is an appealing alternative to RTA-based vaccines, because it is non-toxic and inherently antigenic. However, the degree to which RTB elicits protective immunity against ricin remains unresolved. Here we report that parenteral immunization of mice with RTB elicited high ricin-specific serum antibody titers, yet conferred only partial protection against systemic ricin challenge. Analysis of ~2000 RTB-specific B cell hybridomas identified only a handful of neutralizing monoclonal antibodies (mAbs). Two neutralizing mAbs, 24B11 and SylH3, were shown by passive immunization to be sufficient to protect mice against a 5xLD50 dose of ricin. Both 24B11 and SylH3 blocked ricin attachment to terminal galactose residues and prevented toxin binding to primary macrophages, suggesting that they function by steric hindrance and recognize epitopes located on RTB’s galactose binding sub-domains, 1α or 2γ. By contrast, analysis of four non-neutralizing mAbs revealed that they recognized epitopes situated within sub-domains of RTB not involved in galactose recognition (i.e., 1β, 2α). Based on these data, we propose using specific RTB sub-domains as antigens, rather than RTB itself, as a means to more efficiently elicit neutralizing antibodies and protective immunity against ricin.