Comparison of the quality of protection elicited by toxoid and peptide liposomal vaccine formulations against ricin as assessed by markers of inflammation.
Ricin is a very toxic substance which inhibits protein synthesis and produces 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 vaccine candidates including a formaldehyde inactivated ricin toxoid 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 investigated with a view to improving lung condition following challenge. Using the humoral and local pulmonary immune responses as indices of vaccine performance, no significant difference between toxoid or peptide vaccines was found. In the third and current study, the quality of lung protection by vaccines was assessed using markers of inflammation. Thus, the profiles of inflammatory cell and protein influx into the lung were determined following intratracheal (i.t.) challenge with ricin of rats treated with liposomal vaccine formulations. Results showed that liposomal ricin toxoid offered a better quality of protection with a significantly lower influx of polymorphonuclear leucocytes (neutrophils) and little pulmonary oedema compared with the A chain/liposome formulation. Further, there was no significant difference between the quality of protection offered by the A chain when administered subcutaneously or locally into the lung by i.t. instillation. Liposomal ricin toxoid is a good candidate vaccine and optimised pulmonary delivery by inhalation should be further examined.
Griffiths
G D
GD
Biomedical Sciences Department, DERA, Porton Down, Salisbury, Wiltshire, UK.
Phillips
G J
GJ
Bailey
S C
SC
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D007958:Leukocyte Count; D008081:Liposomes; D009504:Neutrophils / Q000502:physiology; D011506:Proteins / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012276:Ricin / Q000276:immunology* / Q000633:toxicity*; D014121:Toxoids / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014611:Vaccination; D014612:Vaccines / Q000008:administration & dosage*
D008081:Liposomes; D011506:Proteins; D014121:Toxoids; D014409:Tumor Necrosis Factor-alpha; D014612:Vaccines; D012276:Ricin