Comparison of the quality of protection elicited by toroid and peptide liposomal vaccine formulations against ricin as assessed by markers of inflammation

Ricin is a very toxic substance which inhibits protein synthesis and produc es severe tissue damage and inflammation. It is very potent when inhaled as an aerosol and protection has been examined in a series of studies using v accine candidates including a formaldehyde inactivated ricin toroid and the A chain of ricin, a polypeptide equivalent to half of the toxin molecule. Initially, subcutaneous injections of both compounds were found to protect against inhaled ricin but not without some subsequent adverse signs. Intra- pulmonary vaccination using liposomal formulations of these compounds was i nvestigated with a view to improving lung condition following challenge. Us ing the humoral and local pulmonary immune responses as indices of vaccine performance, no significant difference between;een toroid or peptide vaccin es was found. In the third and current study, the quality of lung protectio n by vaccines was assessed using markers of inflammation. Thus, the profile s of inflammatory cell and protein influx into the lung were determined fol lowing intratracheal (i.t,) challenge with ricin of rats treated with lipos omal vaccine formulations. Results showed that liposomal ricin toroid offer ed a better quality of protection with a significantly lower influx of poly morphonuclear leucocytes (neutrophils) and little pulmonary oedema compared with the A chain/liposome formulation. Further, there was no significant d ifference between the quality of protection offered by the A chain when adm inistered subcutaneously or locally into the lung by i.t. instillation. Lip osomal ricin toroid is a good candidate vaccine and optimised pulmonary del ivery by inhalation should be further examined. (C) 1999 Elsevier Science L td. All rights reserved.