title: Non-clinical safety assessment of single and repeated administration of gE/AS01 zoster vaccine in rabbits.
abstract: HZ/su is an investigational recombinant subunit vaccine for the prevention of shingles, a disease resulting from the reactivation of varicella zoster virus. The vaccine is composed of recombinant varicella zoster virus glycoprotein E (gE), and liposome-based Adjuvant System AS01. To evaluate the potential local and systemic effects of this vaccine, three studies were performed in rabbits. In the first two studies, rabbits received a single intramuscular (IM; study 1) or subcutaneous (SC; study 2) dose of gE/AS01, AS01 alone (in study 2 only) or saline, and the local tolerance was evaluated up to 3 days after administration. Under these conditions, only local inflammatory reactions at the injection sites were detected by microscopic evaluation. In the third study, gE/AS01, AS01 alone or saline, were injected SC or IM on four occasions at 2 week intervals. General health status, local tolerance, ophthalmology, haematology and blood chemistry parameters were monitored. Macroscopic and microscopic evaluations were performed after termination of the study. The only treatment-related changes included a transient increase in neutrophils, C-reactive protein and fibrinogen levels and microscopic signs of inflammation at the injection sites, which are expected observations related to the elicited inflammatory reaction. The SC and IM routes of administration produced similar systemic effects. However, microscopic findings at the injection sites differed. One month after the last injection, recovery was complete in all groups. In conclusion, the single and repeated SC and IM administration of the gE/AS01 vaccine were locally and systemically well-tolerated in rabbits and support the clinical development of the vaccine. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Giulia
authors.initials: G
authors.lastname: Giordano
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Segal
authors.affiliation: TNO Triskelion, Zeist, The Netherlands.
authors.forename: Menk
authors.initials: M
authors.lastname: Prinsen
authors.affiliation: TNO Triskelion, Zeist, The Netherlands.
authors.forename: Marcel V W
authors.initials: MV
authors.lastname: Wijnands
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Garçon
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Destexhe
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004353:Drug Evaluation, Preclinical; D005260:Female; D006562:Herpes Zoster / Q000276:immunology / Q000517:prevention & control*; D053061:Herpes Zoster Vaccine / Q000008:administration & dosage* / Q000009:adverse effects* / Q000276:immunology; D000075662:Injection Site Reaction / Q000209:etiology; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008297:Male; D011817:Rabbits; D023382:Toxicity Tests, Acute; D059551:Toxicity Tests, Subacute; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D053061:Herpes Zoster Vaccine; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; C056913:glycoprotein E, varicella-zoster virus
keywords: AS01; Adjuvant System; vaccine, toxicity; varicella-zoster virus