Sub-acute toxicity study in female ICR mice following repetitive intramuscular injection of cervical cancer vaccines

Abstract

ObjectivesThe sub-acute toxic effects following repetitive intramuscular injection of two cervical cancer vaccines newly developed against human papillomaviruse (HPV)16/58/18 and HPV16 were investigated in female ICR (CrljOri: CD1) mice, and the no-observedadverse-effect-level (NOAEL) of the cervical cancer vaccines was estimated. Methods Female ICR mice (n=15 in each group) were exposed to a 1:1 mixture of two cervical cancer vaccines by repetitive intramuscular injection (once a week, 5 times) for 5 weeks. Mortality, body weight, organ weight, hematological/biochemical parameters, and histopathological effects were examined at different concentrations (0, 1 × 10 8 , 5 × 10 8 , and 2.5 × 10 9 copies/animal) of the cervical cancer vaccines. Results The cervical cancer vaccines did not show toxic responses for body weight, absolute/relative organ weight, hematological/biochemical parameters, or histopathological parameters. Conclusions Female ICR mice exposed to vaccines for cervical cancer did not show any toxic response. We suggest that a NOAEL of the vaccine following repetitive intramuscular injection for 5 weeks is > 2.5 × 10 9 copies/animal.