Evaluate the Efficacy, Immunogenicity and Safety of 9-valent HPV Recombinant Vaccine in Chinese Healthy Females

Inclusion Criteria:

(If the "*" option is not met during screening, the visit can be rescheduled)

• Chinese women aged 20-45 who can provide legal identification and have a sexual lifehistory;

• The subject fully understands the study procedures, understands the risks andbenefits associated with participating in the study, and voluntarily signs theinformed consent;

• Subjects are able to read, understand and fill in application forms such as diaryCARDS and contact CARDS, and participate in follow-up according to the studyrequirements;

• Subjects have not been screened for cervical cancer, or have been screened forcervical cancer but the results are normal;

• *0 days before the gynecological visit, no sex within 48 hours, no flushing orvaginal cleaning within 72 hours, no use of vaginal drugs or preparations;Subjectagrees to refrain from sexual intercourse (including anal, vaginal, orgenital/genital contact of the same or opposite sex) for 48 hours prior to any visitthat includes gynecological sample collection, and to refrain from vaginal flushing,vaginal cleansing, or use of vaginal medications or preparations for 72 hours;

• When the subjects were enrolled, the urine pregnancy test was negative (sensitivitywas 25mIU/ml cox-hcg), they were not in the lactation period and had no familyplanning within 7 months after enrollment (1 month before whole-courseinoculation).2 weeks before included in the study, effective contraceptive measureshas been adopted and agreed to in the first seven months after the study (vaccinations after 1 months ago) continue to adopt effective contraceptive measures (effective contraceptive measures include: the pill, injection or embeddedcontraception, slow-release local birth control pills, hormone patch, theintrauterine device (IUD), sterilization, abstinence, condom (men), diaphragm,cervical cap, etc.), rhythm, withdrawal and emergency contraception is unacceptablecontraception;

• *body temperature <37.3℃ (underarm body temperature)

Exclusion Criteria:

First dose exclusion criteria(If the "*" option is met during screening, the visit can be rescheduled)

• Have been vaccinated with commercially available HPV vaccine in the past or plannedto be vaccinated with commercially available HPV vaccine during the study period;Orhave participated in a clinical trial of the HPV vaccine and have received avaccine/placebo vaccination;

• Previous positive history of HPV;

• Has a history of abnormal cervical cytology, including squamous intraepitheliallesions (SIL) or not clear meaning of the atypical squamous cells (ASC - US), exceptthe atypical squamous cells - not highly squamous intraepithelial lesion (ASC - H),atypical glandular epithelial cells, or those with cervical intraepithelialneoplasia (CIN) and carcinoma in situ or abnormal cervical biopsy results such asthe history;

• Past history of anal and genital diseases (such as vulvar intraepithelial neoplasia,vaginal intraepithelial neoplasia, genital warts, vulvar cancer, vaginal cancer andanal cancer, etc.);

• Received total hysterectomy or pelvic radiotherapy;

• Cervical insufficiency or abnormal cervical structure (judged by the results ofroutine gynecological examination);

• Previous sexual history (including syphilis, gonorrhea, chancre, venereal lymphaticgranuloma, granuloma inguinal) or have obvious condyloma;

• A history of seizures, convulsions or convulsions, or a family history of mentalillness;

• Have participated in other gynecology-related clinical trials within 6 months, andhave used or plan to use other investigational or unregistered products (drugs orvaccines) other than the vaccine in this study within 3 months;

• A history of severe allergies requiring medical intervention, such as anaphylacticshock, anaphylactic laryngeal edema, allergic purpura, thrombocytopenic purpura,local allergic necrosis reaction (Arthus reaction), etc.A history of severe adversereactions to previous vaccinations or a history of severe allergies to any of thecomponents of the vaccine under study (histidine, polysorbate, aluminum phosphate,sodium borate, amorphous aluminum phosphate sulfate adjuvant and water forinjection) (such as swelling of the mouth and throat, dyspnea, hypotension or shock,severe urticaria, etc.);

• Subject receives any immunoglobulin or blood product within 3 months prior to thefirst dose of vaccination, or plans to receive such product within the next 7 months (1 month prior to the full course of vaccination);

• Subjects present/present with immune impairment or have been diagnosed withcongenital or acquired immune deficiency, HIV infection, lymphoma, leukemia,systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoidarthritis (JRA), inflammatory bowel disease or other autoimmune diseases;

• Immunosuppressant therapy within 1 month before the first dose of vaccination, suchas long-term use of systemic glucocorticoid therapy (≥2mg/kg/ day, for more than 2weeks, such as prednisone or similar drugs;Topical administration (such as ointment,eye drops, inhalant or nasal spray) not exceeding the recommended dosage in thedirections or showing any signs of systemic exposure) or planning to receive suchtreatment within the next 7 months (1 month before the full course of inoculation);

• Absence of spleen or functional absence of spleen, and absence of spleen orsplenectomy in any case;

• Patients with severe liver, kidney and cardiovascular diseases, diabetes ormalignant tumor with complications;

• Patients with thrombocytopenia or any coagulation disorders that may becontraindications to intramuscular injection;

• • subjects received inactivated or recombinant vaccines within 14 days prior tostudy enrollment, or attenuated live vaccines within 28 days prior to studyenrollment;
• • an acute illness or an acute episode of a chronic illness within 3 days prior tovaccination or the use of antipyretic, analgesic and antiallergic drugs (e.g.,acetaminophen, ibuprofen, aspirin, loratadine, cetirizine, etc.);
• • the first dose of vaccine was in pregnancy at the time of vaccination, or the endof pregnancy had not exceeded 6 weeks;
• • after questioning, subjects had fever symptoms (subaxillary body temperature ≥37.3℃) before the first day of vaccination (within 24 hours before vaccination);
• • the subject is in the menstrual period;
• • severe acute vaginitis and suppurative cervicitis found by naked eye duringgynecological examination (purulent secretion visible by naked eye);

• Blood pressure on physical examination before the first dose of vaccination washigher than normal or increased (systolic blood pressure ≥140mmHg and/or diastolicblood pressure ≥90mmHg);

• Gynecological examination before the first dose of vaccination suspected genitalwarts, or on the basis of clinical symptoms and signs suspected vulva, vagina orcervical precancerous lesions and the possibility of cancer;

• Subjects may be unable to comply with the study procedure, comply with theagreement, or plan to permanently relocate from the region prior to completion ofthe study, or may be permanently absent from the region during the scheduled visit;

• In the opinion of the investigators, the subjects had any other factors that madethem unsuitable to participate in the clinical trial, so that continuedparticipation in the study could not guarantee the maximum benefit of the subjects.

Second and third doses of vaccine were excluded criteria

• new discoveries or new occurrences that meet the first dose exclusion criteria (except for articles 2, 3, 4, 21);

• other serious adverse events: the investigator decides whether to terminate theexperimental vaccination according to its treatment needs;

• the investigator assays for any other reasons that may be considered necessary toterminate the trial vaccination.

Second and third doses of vaccine were delayed criteria

Vaccination may be postponed if:

• fever (underarm body temperature ≥37.3℃);

• before inoculation (on the day of inoculation), the urine pregnancy test waspositive (sensitivity was 25mIU/ml n-hcg);

• acute illness or acute attack of a chronic disease or use of antipyretic, analgesicand antiallergic drugs (e.g., acetaminophen, ibuprofen, aspirin, loratadine,cetirizine, etc.) within 3 days before vaccination;

• insufficient interval between other vaccines (inactivated or recombinant vaccinesreceived within 14 days prior to vaccination, or any live attenuated vaccinereceived within 28 days);

• any immunoglobulin or blood products received during vaccination should beadministered at least 3 months after the vaccination;

• other circumstances that can be postponed as judged by the researcher.