The Safety And Immunogenicity Studies Of Recombinant Human Papillomavirus Nine-valent Vaccine

Human papillomavirus(HPV)belong to papilloma vacuolar virus A of papovaviridae,which is spherical DNA virus that can induce the proliferation of squamous epithelial of human skin mucosa,its main clinical symptoms are common sputum,genital warts(condyloma acuminata)and other symptoms.With the rapid rise of the incidence of condyloma acuminata and the increase in cervical cancer and anal cancer in sexually transmitted disease,HPV infection has seriously endangered human health,especially bringing enormous social and economic burden to developing countries,the development of vaccines is the most effective way to prevent and treat HPV infection and its related diseases.This project was to evaluate the safety and immunogenicity of recombinant human papillomavirus 6/11/16/18/31/33/45/52/58 nine-valent vaccine(recombinant HPV nine-valent vaccine)by animal experiments.It is essential for clinically experiments and listing of recombinant HPV nine-valent vaccine to carry out the necessary preclinical toxicology studies.The single-dose toxicity test of SD rats with intramuscular injection of recombinant HPV nine-valent vaccine showed that after SD rats were administered in single dose of 2 people,the rats showed no obvious clinical symptoms and chanages in body weight and weight gain rates.At the end of the recovery period,the surviving rats were dissected generally showed no significant pathological changes.The results of repeated dose toxicity test of SD rats injected intramuscularly with recombinant HPV nine-valent vaccine showed: After multiple doses of this vaccine in a 0.5doses and 1 dose of 1 people respectively,the administration site of SD rats showed obvious irritation,EOS and EOS% increased in hematologic indicators.After multiple doses of this vaccine in 1 dose of 1 people,the hematological index of rats showed that MONO% rose,and the number of ALP and ALB decreased in serum biochemical.The above-mentioned toxicity indicators were reversible.SD rats were intramuscularly injected recombinant HPV nine-valent vaccine in fertility and early embryo test,and embryo-foetuses growth toxicity test results showed: After the rats were administered in 0.5 doses and 1 dose of 1 people respectively,parental male and female rats showed no obvious toxicity;foetuses was not observed in teratogenic toxicity.The results of perinatal toxicity test of SD rats with intramuscular injection ofrecombinant HPV nine-valent vaccine showed that: No significant toxicity was observed in newborn rats,and parental male and female rats after repeated administration of 0.5 and 1dose of 1 people repestively.After SD rats were injected intramuscularly recombinant HPV nine-valent vaccine 0.5and 1 doses of 1 people respectively,the HPV6,HPV11,HPV16,HPV18,HPV31,HPV33,HPV45,HPV52 and HPV58 in serum of rats administrated with vaccine was positive in antibody test(the inhibition rate of pseudovirus infection was ?50% after serum samples were diluted 80-fold),the HPV16?HPV18?HPV31?HPV33?HPV45?HPV52 and HPV58 taken from serum of newborn rats was positive.The detection of HPV6 and HPV11 was negative in fewer nest,the rest is positive.These results suggested that the recombinant HPV nine-valent vaccine had good immunogenicity in SD rats.