Initial preclinical safety of non‐replicating human endogenous retrovirus envelope protein‐coated baculovirus vector‐based vaccines against human papillomavirus

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. Copyright © 2012 John Wiley & Sons, Ltd.