Long-term toxicity, pharmacokinetics and immune effects of a recombinant adenovirus vaccine expressing human papillomavirus 16 E6 and E7 proteins (HPV16 E6E7-Ad5 Vac) in primates.

OBJECTIVE: This study aimed to: evaluate long-term toxicity and pharmacokinetic parameters; to identify the target organ of toxicity of a recombinant adenovirus vaccine expressing human papillomavirus 16 E6 and E7 proteins (HPV16 E6E7-Ad5 Vac) in primates; and to determine the specific immune response of this recombinant adenovirus vaccine.

METHOD: HPV16 E6E7-Ad5 Vac (dose 4.68 × 109 IU/bottle) was administered to Macaca fascicularis ( M. fascicularis ) to evaluate its long-term toxicity. The Cynomolgus Monkeys were divided into a negative control group (sodium chloride injection group), a low-dose group (4.68 × 108 IU/macaque), and, a high-dose group (4.68 × 109 IU/macaque). The drugs were administered at intervals of once every three weeks (D1, D21, D42). The macaques were observed until the sixth week of the recovery period (D84) for safety and toxicological indicators and pharmacokinetic indicators. To study the specific immune response in Rhesus Macaque, empty viruses (rAd5-null) and buffer were inoculated as controls, respectively. Two doses of the vaccine were given at 1.0 × 108 IU/ml and 1.0 × 109 IU/ml and theHPV-16 E6-/HPV-16 E7-specific IFN-γ productions were measured.

RESULTS: The macaques of both the high-dose group and the low-dose group did not exhibit any systemic toxic response. The administered safe dose of the vaccine was 4.68 × 109 IU per animal. Following vaccination, HPV16 E6/E7-specific antibodies were observed to be generated in both groups, indicating an immune response of the lymphocytes targeting HPV16 E6 and HPV16 E7 epitopes (specific NF-r) was elicited. The peak level of HPV-16 E6-/HPV-16 E7-specific IFN-γ production was observed in the ninth week.