title: Repeated dose (14 days) rat intramuscular toxicology study of Her1 vaccine.
abstract: Our goal was to assess the toxicity of two strengths (200 and 400 μg) of HER1 cancer vaccine (Center of Molecular Immunology, Cuba), presented in two different formulations, in Sprague Dawley rats after repeated intramuscular administration (14 days). Four groups (5 animals/sex) were established: Control, Placebo (adjuvant), and two Treated groups receiving a dose representing ten times of human total dose (10×), 28.6 and 57.1 μg/kg. Clinical observations, body weight and rectal temperature were measured during the study. Clinical pathology analysis was performed, besides gross necropsy and histological examination of tissues on animals at the end of the assay. The assay ended with a 100% survival. Injection site damage, with the presence of cysts and granulomas, was observed in adjuvant and vaccine treated groups, with most severe cases predominating at higher strength. Administration of Placebo and Her1 vaccine induced increase in polymorphonuclear cells, with relative lymphopenia conditioned by primary neutrophilia. In summary, results suggest that Her1 immunization was capable of inducing an inflammatory effect at the injection site, leading to systemic alterations, more significant at higher strength (400 μg, 57.1 μg/kg), probably affected by the immunizations' schedule used. The vaccine was shown to be well tolerated without any obvious signs of systemic toxicity, with findings largely attributable to the adjuvant used.
authors.affiliation: National Center for Laboratory Animals Breeding (CENPALAB), Habana, Cuba. axelm@cenpalab.inf.cu
authors.forename: A
authors.initials: A
authors.lastname: Mancebo
authors.forename: A
authors.initials: A
authors.lastname: Casacó
authors.forename: B
authors.initials: B
authors.lastname: Sánchez
authors.forename: B
authors.initials: B
authors.lastname: González
authors.forename: D
authors.initials: D
authors.lastname: Gómez
authors.forename: A
authors.initials: A
authors.lastname: León
authors.forename: A M
authors.initials: AM
authors.lastname: Bada
authors.forename: M E
authors.initials: ME
authors.lastname: Arteaga
authors.forename: Y
authors.initials: Y
authors.lastname: González
authors.forename: C
authors.initials: C
authors.lastname: González
authors.forename: M
authors.initials: M
authors.lastname: Pupo
authors.forename: Dasha
authors.initials: D
authors.lastname: Fuentes
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004815:Epidermal Growth Factor / Q000276:immunology*; D005260:Female; D007249:Inflammation / Q000139:chemically induced*; D007273:Injections, Intramuscular; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019496:Cancer Vaccines; D004815:Epidermal Growth Factor