LOCAL AND SYSTEMIC RESPONSES AGAINST RICIN TOXIN PROMOTED BY TOXOID OR PEPTIDE VACCINES ALONE OR IN LIPOSOMAL FORMULATIONS

The objective of this study was to develop a vaccine which would ultim ately protect mart from the lethal effects of inhaled ricin toxin. Por ton rats have previously been protected from lethal quantities of inha led ricin by subcutaneous (s.c.) ricin toxoid vaccine but not without lung damage, This situation might be improved by an alternative vaccin e such as the A chain of ricin, already known to protect against inhal ed ricin. Another option would be to improve respiratory tract immunit y by local vaccination in conjunction with liposomal formulation with a view to enhancing lung secretion of immune IgA. While boosted s.c. d oses of ricin toroid or A chain produced indistinguishable systemic im mune responses 3 weeks later, when delivered by the intratracheal (i.t .) route, the A chain failed to elicit a specific immune response, unl ike ricin toroid This situation was overcome by liposomal formulations and although ricin toxoid, This readily encapsulated in liposomes, A chain was not However by simply mixing A chain and liposomes in the sa me weight ratio determined for liposomal toroid systemic immune respon ses for each formulation were indistinguishable 1 week after boosting. Ricin antibody responses in lung fluid monitored 1, 3, 7 and 14 days after i.t. challenge with ricin were statistically indistinguishable, but the group vaccinated with liposomal toroid secreted 28.7% IgA comp ared with 0.9-14.9% for the A chain liposomal group. From this, it mig ht be anticipated that the lungs would be better protected by liposoma lly-encapsulated ricin toroid than by the A chain-liposome mixture. Cr own Copyright (C) 1998 Published by Elsevier Science Ltd.