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 ultimately protect man from the lethal effects of inhaled ricin toxin. Porton rats have previously been protected from lethal quantities of inhaled ricin by subcutaneous (s.c.) ricin toxoid vaccine, but not without lung damage. This situation might be improved by an alternative vaccine such as the A chain of ricin, already known to protect against inhaled ricin. Another option would be to improve respiratory tract immunity by local vaccination in conjunction with liposomal formulation with a view to enhancing lung secretion of immune IgA. While boosted s.c. doses of ricin toxoid or A chain produced indistinguishable systemic immune responses 3 weeks later, when delivered by the intratracheal (i.t.) route, the A chain failed to elicit a specific immune response, unlike ricin toxoid. This situation was overcome by liposomal formulations and although ricin toxoid was readily encapsulated in liposomes, A chain was not. However, by simply mixing A chain and liposomes in the same weight ratio determined for liposomal toxoid, systemic immune responses 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 toxoid secreted 28.7% IgA compared with 0.9-14.9% for the A chain liposomal group. From this, it might be anticipated that the lungs would be better protected by liposomally-encapsulated ricin toxoid than by the A chain-liposome mixture.
Griffiths
G D
GD
Medical Countermeasures Department, Chemical and Biological Defence, Porton Down, Salisbury, Wiltshire, UK.
Bailey
S C
SC
Hambrook
J L
JL
Keyte
M P
MP
D000818:Animals; D000917:Antibody Formation; D001992:Bronchoalveolar Lavage Fluid; D007279:Injections, Subcutaneous; D007442:Intubation, Intratracheal; D008081:Liposomes; D008297:Male; D010455:Peptides / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D012276:Ricin / Q000276:immunology*; D014121:Toxoids / Q000627:therapeutic use*; D014614:Vaccines, Synthetic / Q000627:therapeutic use*
D008081:Liposomes; D010455:Peptides; D014121:Toxoids; D014614:Vaccines, Synthetic; D012276:Ricin