title: Liposomally-encapsulated ricin toxoid vaccine delivered intratracheally elicits a good immune response and protects against a lethal pulmonary dose of ricin toxin.
abstract: A small study was performed to examine whether the instillation of ricin toxoid vaccine into the lungs of Porton rats offered protection from lethal effects of subsequent intratracheal challenge with ricin toxin. Further the immune response to liposomally-encapsulated vaccine and the protection offered was compared with vaccine either adsorbed to Alhydrogel adjuvant or as a simple aqueous solution. The formaldehyde-treated ricin toxin vaccine (RTV) was administered at two dose levels, 500 and 100 micrograms kg-1 body weight to groups of rats, on two occasions by intratracheal instillation. Liposomally-encapsulated vaccine (LRTV) produced a higher titre of ricin-specific antibodies than Alhydrogel-vaccine (ARTV) and vaccine solution. When challenged with 3 LD50 of ricin by intratracheal instillation 7 weeks after the second vaccine instillation, all rats in both LRTV dose groups survived with minimal signs of incapacitation. Analysis of antibody secretion by spleen cells, 14 days post challenge, showed that the IgG isotype in the LRTV group was significantly higher than that in the ARTV and RTV groups and also that the proportion of specific IgA in lung fluid was higher in the LRTV group than in the ARTV and RTV groups. The results of this study indicate that effective vaccinations against inhaled ricin could be achieved with liposomally-encapsulated ricin toxoid, via the lung and should be investigated further.
authors.affiliation: Medical Countermeasures, Porton Down, Salisbury, UK.
authors.forename: G D
authors.initials: GD
authors.lastname: Griffiths
authors.forename: S C
authors.initials: SC
authors.lastname: Bailey
authors.forename: J L
authors.initials: JL
authors.lastname: Hambrook
authors.forename: M
authors.initials: M
authors.lastname: Keyte
authors.forename: P
authors.initials: P
authors.lastname: Jayasekera
authors.forename: J
authors.initials: J
authors.lastname: Miles
authors.forename: E
authors.initials: E
authors.lastname: Williamson
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D004333:Drug Administration Routes; D007132:Immunoglobulin Isotypes / Q000097:blood; D008081:Liposomes; D008171:Lung Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012276:Ricin / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity; D014121:Toxoids / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity; D014132:Trachea; D014612:Vaccines / Q000008:administration & dosage
chemical_list: D000906:Antibodies; D007132:Immunoglobulin Isotypes; D008081:Liposomes; D014121:Toxoids; D014612:Vaccines; D012276:Ricin