title: Initial preclinical safety of non-replicating human endogenous retrovirus envelope protein-coated baculovirus vector-based vaccines against human papillomavirus.
abstract: Human endogenous retrovirus (HERV) envelope protein-coated, baculovirus vector-based HPV 16 L1 (AcHERV-HPV16L1) is a non-replicating recombinant baculoviral vaccine. Here, we report an initial evaluation of the preclinical safety of AcHERV-HPV16L1 vaccine. In an acute toxicity study, a single administration of AcHERV-HPV16L1 DNA vaccine given intramuscularly (i.m.) to mice at a dose of 1 × 10(8) plaque-forming units (PFU) did not cause significant changes in body weight compared with vehicle-treated controls. It did cause a brief increase in the weights of some organs on day 15 post-treatment, but by day 30, all organ weights were not significantly different from those in the vehicle-treated control group. No hematological changes were observed on day 30 post-treatment. In a range-finding toxicity study with three doses of 1 × 10(7) , 2 × 10(7) and 5 × 10(7) PFU once daily for 5 days, the group treated with 5 × 10(7) PFU showed a transient decrease in the body weights from day 5 to day 15 post-treatment, but recovery to the levels similar to those in the vehicle-treated control group by post-treatment day 20. Organ weights were slightly higher for lymph nodes, spleen, thymus and liver after repeated dosing with 5 × 10(7) PFU on day 15, but had normalized by day 30. Moreover, repeated administration of AcHERV-HPV16L1 did not induce myosin-specific autoantibody in serum, and did not cause immune complex deposition or tissue damage at injection sites. Taken together, these results provide preliminary evidence of the preclinical safety of AcHERV-based HPV16L1 DNA vaccines in mice.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, Korea.
authors.forename: Su-Eun
authors.initials: SE
authors.lastname: Han
authors.forename: Mi-Gyeong
authors.initials: MG
authors.lastname: Kim
authors.forename: Soondong
authors.initials: S
authors.lastname: Lee
authors.forename: Hee-Jeong
authors.initials: HJ
authors.lastname: Cho
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
authors.forename: Sujeong
authors.initials: S
authors.lastname: Kim
authors.forename: Young Bong
authors.initials: YB
authors.lastname: Kim
authors.forename: Yongseok
authors.initials: Y
authors.lastname: Choi
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood; D016367:Baculoviridae / Q000235:genetics*; D001835:Body Weight / Q000187:drug effects; D036022:Capsid Proteins / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D020077:Endogenous Retroviruses / Q000235:genetics*; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D009929:Organ Size / Q000187:drug effects; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D061987:Sf9 Cells; D018411:Spodoptera / Q000821:virology; D023382:Toxicity Tests, Acute; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D014759:Viral Envelope Proteins / Q000235:genetics*
chemical_list: D001323:Autoantibodies; D036022:Capsid Proteins; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; C063317:L1 protein, Human papillomavirus type 16