title: Effects of Adjuvant Systems on the cardiovascular and respiratory functions in telemetered conscious dogs and anaesthetised rats.
abstract: Adjuvants Systems (AS) containing immunostimulant combinations are used in human vaccines. Safety pharmacology studies evaluated the cardiorespiratory effects of AS in conscious telemetered dogs and in anaesthetised rats. Sixteen telemetered beagle dogs (4/group) received intramuscular injections of saline at Day 0, and one clinical dose of AS01, AS03, AS04 or AS15 at Day 7 (7× the equivalent human dose on a bodyweight basis). Bodyweights were measured through Day 14 and cardiorespiratory parameters and body temperature through 72 h post-treatment. Anaesthetised rats (4/group) received one intravenous injection of AS01, AS03 or AS15 at 1 mL/kg bodyweight (140× the equivalent human dosages), or saline. Cardiorespiratory parameters were measured for 120 min post-dose. In dogs, food consumption and mean bodyweight decreased with AS03, and mean body temperature slightly increased with AS01, AS03 and AS15, but were not considered to be adverse. Cardiovascular effects (a slight, reversible increase in mean heart rate and shortened mean RR/PR/QT-intervals) were observed with AS15. No relevant clinical effects or effects on QRS-complex/QTc-interval durations, arterial pressure or respiratory parameters were observed. In rats, there were no consistent treatment-related effects. Collectively, this suggests that AS01, AS03, AS04 and AS15 are not associated with potentially deleterious effects on ventricular repolarisation, atrio/intra-ventricular conductivities or respiratory functions.
authors.affiliation: GSK Vaccines, Rue Fleming 20, 1300 Wavre, Belgium. Electronic address: lawrence.m.segal@gsk.com.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Segal
authors.affiliation: WIL Research Europe-Lyon, 329 impasse du Domaine Rozier, 69210 Saint-Germain-Nuelles, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Roger
authors.affiliation: Huntingdon Life Sciences Ltd, Woolley Road Alconbury, Huntingdon, Cambridgeshire PE28 4HS, UK.
authors.forename: Colin
authors.initials: C
authors.lastname: Williams
authors.affiliation: GSK Vaccines, Rue de l'Institut 89, 1330 Rixensart, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Destexhe
authors.affiliation: GSK Vaccines, Rue de l'Institut 89, 1330 Rixensart, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Garçon
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D003243:Consciousness / Q000187:drug effects*; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects*; D013686:Telemetry / Q000379:methods
chemical_list: D000276:Adjuvants, Immunologic
keywords: AS01; AS03; AS04; AS15; Adjuvant System; Cardiovascular; Dog; Rat; Respiratory; Telemetry