title: Repeated high-dose (5 × 10(8) TCID50) toxicity study of a third generation smallpox vaccine (IMVAMUNE) in New Zealand white rabbits.
abstract: Concern over the release of variola virus as an agent of bioterrorism remains high and a rapid vaccination regimen is desirable for use in the event of a confirmed release of virus. A single, high-dose (5×10(8) TCID50) of Bavarian Nordic's IMVAMUNE was tested in a Phase-II clinical trial, in humans, as a substitute for the standard (1×10(8) TCID50), using a 2-dose, 28-days apart regimen. Prior to this clinical trial taking place a Good Laboratory Practice, repeated high-dose, toxicology study was performed using IMVAMUNE, in New Zealand white rabbits and the results are reported here. Male and female rabbits were dosed twice, subcutaneously, with 5×10(8) TCID50 of IMVAMUNE (test) or saline (control), 7-days apart. The clinical condition, body-weight, food consumption, haematology, blood chemistry, immunogenicity, organ-weight, and macroscopic and microscopic pathology were investigated. Haematological investigations indicated changes within the white blood cell profile that were attributed to treatment with IMVAMUNE; these comprised slight increases in neutrophil and monocyte numbers, on study days 1-3 and a marginal increase in lymphocyte numbers on day 10. Macroscopic pathology revealed reddening at the sites of administration and thickened skin in IMVAMUNE, treated animals. After the second dose of IMVAMUNE 9/10 rabbits seroconverted, as detected by antibody ELISA on day 10, by day 21, 10/10 rabbits seroconverted. Treatment-related changes were not detected in other parameters. In conclusion, the subcutaneous injection of 2 high-doses of IMVAMUNE, to rabbits, was well tolerated producing only minor changes at the site of administration. Vaccinia-specific antibodies were raised in IMVAMUNE-vaccinated rabbits only.
authors.affiliation: a National Infection Service, Public Health England , Porton Down, Salisbury , Wiltshire , UK.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Tree
authors.affiliation: a National Infection Service, Public Health England , Porton Down, Salisbury , Wiltshire , UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Hall
authors.affiliation: b Envigo CRS Limited , Occold, Eye , Suffolk , UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Rees
authors.affiliation: a National Infection Service, Public Health England , Porton Down, Salisbury , Wiltshire , UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Vipond
authors.affiliation: a National Infection Service, Public Health England , Porton Down, Salisbury , Wiltshire , UK.
authors.forename: Simon G P
authors.initials: SG
authors.lastname: Funnell
authors.affiliation: a National Infection Service, Public Health England , Porton Down, Salisbury , Wiltshire , UK.
authors.forename: Allen D
authors.initials: AD
authors.lastname: Roberts
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007279:Injections, Subcutaneous; D008297:Male; D011817:Rabbits; D012900:Smallpox Vaccine / Q000008:administration & dosage* / Q000009:adverse effects*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000914:Antibodies, Viral; D012900:Smallpox Vaccine; D014613:Vaccines, Attenuated; C527606:smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic
keywords: IMVAMUNE; MVA; rabbits; smallpox; toxicology; vaccine
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