Safety Study of Recombinant Human Papillomavirus Vaccine(6,11,16,18,31,33,45,52,58 Type)(E.Coli)

The study would have 2 stages. In the first stage, around 12 healthy adults aged 18-45 (male vs female,around 1:1)would receive 135μg/0.5ml of the HPV vaccine, the participants would be actively followed up for 7 days, if no vaccine related serious adverse events(SAE) occurred and the vaccine is well tolerated, another group of 12 healthy adults aged 18-45 (male vs female,around 1:1)would be enrolled and would receive 270μg/0.5ml of the HPV vaccine. The vaccine would be administered intramuscularly at day 0, month 1 and month 6. All the participants would be actively monitored for adverse reactions/events for 1 month after each injection. SAE during the trial were followed up. And blood, liver and kidney function changes will be monitored before and 2 days after the first and third vaccination. Serum samples from all the subjects would be collected on day 0 and month 7 to test immunogenicity as exploratory analysis.

Inclusion criteria

• Health people aged between 18 and 45 years.
• Judged as healthy and eligible for vaccination by the investigators through a self-reported medical history and some physical examinations.
• Able to comply with the requests of the study.
• Written informed consent obtained from the participants.
• Axillary temperature not higher than 37.0°C
• Men, or non-pregnant women verified by a urine pregnancy test.

Exclusion criteria

• Pregnant or breastfeeding or plan to be pregnant within 7 months.
• Use of any investigational product or non-registered product (drug or vaccine) within 30 days preceding the first dose of the study vaccine or plan to use during the study period.
• Received immunosuppressed, immunoregulation therapy or corticosteroid systemic therapy for more than 14 days in the 6 months before entry, except local treatment.
• Administration of any immunoglobulin or blood products within 3 months preceding the first dose of the study vaccine or plan to use within 7 months.
• Administration of any attenuated live vaccines within 21 days preceding the first dose of the study vaccine or any subunit or inactivated vaccines within 14 days before vaccination.
• Had a fever (axillary temperature over 38°C) within 3 days or acute illness requiring systemic antibiotics or antiviral treatment within 5 days before vaccination.
• Having the plan to participate another clinical trial during the study period.
• Received another HPV vaccine.
• Immunodeficiency , primary disease of important organs, malignant tumor, or any immune disease (such as systemic lupus erythematosus, arthritis pauperum, splenectomy or functional asplenia or other disease which might affect immune response).
• History of allergic disease or history of serious adverse events occurring after vaccination, i.e., allergy, urticaria, dyspnea, angioneurotic edema or abdominal pain.
• Asthma that required emergent treatment, hospitalization, oral or intravenous corticosteroid for unstable condition within the past 2 years.
• Having serious disease of internal medicine, such as hypertension(systolic blood pressure > 140mmHg or diastolic blood pressure >90mmHg), cardiac disease, diabetes, hyperthyroidism et al.
• Diagnosed coagulant function abnormality or blood coagulation disorder. 14) The results of blood routine test and blood biochemical test were abnormal. The grade was 2 or above.

• Epilepsy, except fever epilepsy at under 2 years of age, alcohol-induced epilepsy in 3 years before abstinence, or idiopathic epilepsy requiring no treatment in the past 3 years.

• Past or current two-stage affective psychosis, not well controlled in the past 2 years or requiring drugs, or hve a tendency to commit suicide in the past 5 years.

• Other medical, psychological, social or occupational factors that, according to the investigators' judgment, might affect the individual's ability to obey the protocol or sign the informed consent.