PROTECTION AGAINST RICIN INTOXICATION IN-VIVO BY ANTIIDIOTYPE VACCINATION

A BALB/c murine anti-ricin monoclonal antibody (mAb BG11-G2, IgG(1k)), was recently isolated and shown to passively protect syngeneic mice a gainst ricin intoxication in vivo. New Zealand White rabbit polyclonal anti-idiotype (anti-Id) antibodies were raised to BG11-G2 anti-ricin mAb, and rendered specific by repeated absorption over agarose-normal mouse immunoglobulin (Ig). The absorbed rabbit anti-Id antibodies lost reactivity to normal mouse Ig and to a BALB/c anti-T-2 mycotoxin IgG( 1k) mAb (HD11), but remained reactive with BG11-G2 anti-ricin mAb. The rabbit anti-Id inhibited the binding of BG11-G2 mAb to ricin-coated w ells, and elicited a specific and protective anti-ricin antibody respo nse in naive BALB/c mice. Whereas all mice vaccinated with a control r abbit anti-Id antibody preparation died from in vivo ricin challenges, mice immunized with the rabbit anti-Id specific for BG11-G2 mAb were protected to various degrees. All mice vaccinated with rabbit anti-Id to BG11-G2 and challenged with ricin doses of 35 and 50 mu g kg(-1) bo dy weight died from the challenge; however, a delay in the elapsed tim e between ricin administration and death was observed in these mice as compared to that of the control anti-Id-immune mice. Five of seven mi ce vaccinated with the rabbit anti-Id to BG11-G2 and subsequently chal lenged in vivo with a ricin dose of 20 mu g kg(-1) body weight survive d the lethal in vivo ricin challenge, whereas all the control mice die d. The five surviving mice were successively rechallenged with increas ing ricin doses of 50, 150, and 500 mu g kg(-1) body weight, respectiv ely, on days 76, 82 and 92 following the first ricin challenge. All fi ve mice survived the subsequent in vivo ricin rechallenges, and remain ed healthy two months following the last ricin re-challenge, suggestin g an anti-Id-induced priming of an enhanced protective immune response to the nominal antigen, ricin.