A Phase III Study to Evaluate the Efficacy, Immunogenicity and Safety of the 9-valent HPV Vaccine in Chinese Males

Inclusion Criteria:

1. Chinese men aged 18-45 years who can provide legal identification and have a sexuallife history;

2. Subjects fully understands the study procedures, understands the risks and benefitsassociated with participating in the study, and voluntarily signs the informedconsent;

3. Subjects are able to read, understand and fill in the research application formssuch as diary CARDS and contact CARDS, and promise to participate in regularfollow-up according to the study requirements;

4. Heterosexual men subjects must have exclusively female sexual partners and no morethan 5 before enrollment;

5. MSM subject must have had sex with men within the past year (either insertive orreceptive anal intercourse); and the cumulative number of sexual partners (includingmale and female sexual partners) does not exceed 5 before enrollment;

6. Subjects agree to provide effective contact information that can be used forcommunication with the researchers during the study;

7. Subjects consent to external anogenital lesion inspection and sample collection (including but not limited to wet swab collection and necessary biopsy) during thestudy period;

8. Subjects agree to take effective contraceptive measures from the first dose to 1month after the last dose [male effective contraception including abstinence, malecondom, vasectomy, etc.; female valid contraception including the pill (excludingemergency contraception), injection or embedded contraception, sustained-releasetopical contraceptives, hormonal patch, intrauterine devices (IUD), sterilization,diaphragm, cervical caps, etc.; safe period contraception, extracorporealejaculation, and emergency contraception are unacceptable contraception.]

Exclusion Criteria:

Initial inoculation exclusion criteria (If the "*" option is met during screening, the enrollment can be postponed and the re-screening can be rescheduled )

1. • Subjects with axillary temperature ≥37.3℃ 24 hours before the first vaccination;
2. • Higher blood pressure on the day of the first vaccination (systolic blood pressure ≥140mmHg and/or diastolic blood pressure ≥90mmHg);
3. • Sexual activity (including anal, vaginal/genital contact of the same or oppositesex) within 48 hours prior to the sampling visit; Self-shave hair from genital areawithin 24 hours prior to the genital examination visit (and/or using anypost-shaving lotions or lubricants);

4. Have been or planned to be vaccinated with commercially available HPV vaccine; Haveparticipated in or plan to participate in other HPV vaccine clinical trials;

5. Previous positive HPV test results (including types not included in theinvestigational vaccine) or related cytological abnormalities；

6. Previous or current HPV-related genital warts, penile/perianal/perinealintraepithelial neoplasia, penile/perianal/perineal cancer, anal intraepithelialneoplasia, or anal cancer;

7. Significant clinical evidence of external genital lesions and anal diseases (onlyMSM) suggesting the HPV infection during the external anogenital inspection beforethe first vaccination;

8. • Acute illness or acute episode of chronic disease, or use of antipyretic,analgesic and antiallergic drugs (e.g., acetaminophen, ibuprofen, aspirin,loratadine, cetirizine, etc.) within 3 days prior to vaccination;
9. • Received inactivated/recombinant/nucleic acid vaccine (non-attenuated vaccine)within 7 days prior to recruitment, or attenuated vaccine within 14 days prior toenrollment;
10. • Received any immune globulin or blood derived products within 3 months prior toenrollment, or plan to use any between the first vaccination and 1 month after fullimmunization;
11. • Received immunosuppressive therapy within 1 month prior to vaccination, such asimmunosuppressive doses of glucocorticoids (dose reference: equivalent to prednisone 20mg/day for more than 7 days), or monoclonal antibodies, thymosin, interferon,etc., or plan to receive such treatment during the first dose until 1 month afterfull immunization, but topical administration (such as ointment, eye drops,inhalants or nasal sprays) is allowed;

12. Other investigational or unregistered products (drug or vaccine) that have been usedwithin 3 months prior to the first dose or are planned to be used during the studyperiod;

13. Present or have a history of convulsions (except febrile convulsions in childhood (0-14 years)), epilepsy, other serious neurological diseases (such as transversemyelitis, Guillain-Barre syndrome, demyelinating diseases, etc.);

14. Present or have a history of mental illness or the family history;

15. There are contraindications to intramuscular injection, such as having beendiagnosed with thrombocytopenia, any coagulation dysfunction, or being treated withanticoagulants;

16. Any condition resulting in asplenia or functional asplenia；

17. A history of severe allergic reactions requiring medical intervention (such asanaphylactic shock, anaphylactic laryngeal edema, allergic purpura, thrombocytopenicpurpura, local allergic necrosis (Arthus reaction), etc.); A history of severeadverse reactions to previous vaccination or a history of severe allergies (e.g.mouth and throat swelling, dyspnea, hypotension or shock, severe urticaria, etc.) toany vaccine component (histidine, sodium chloride, polysorbate 80, aluminumphosphate adjuvant and water for injection) ;

18. Subjects have been diagnosed with congenital or acquired immunodeficiency disease,such as: AIDS, lymphoma, leukemia, systemic lupus erythematosus, rheumatoidarthritis, juvenile rheumatoid arthritis, inflammatory bowel disease or other immunedisorders;

19. Currently have a serious infectious disease such as active tuberculosis, activeviral hepatitis or acquired immunodeficiency syndrome (HIV infection);

20. Diagnosed with a serious congenital malformation or chronic disease that mayinterfere with the conduct or completion of the study, such as Down syndrome, heartdisease, liver disease, kidney disease, diabetes with complications, or malignanttumors;

21. A history of drug abuse prior to enrolling, or a history of drug or alcohol abuse ordependence within the last year;

22. Subjects plan to permanently relocate from the region before the completion of thestudy or leave the region for a long period of time during the scheduled visit (affecting the scheduled visit time);

23. Investigators consider that the subjects have any condition that may interfere withthe evaluation of the objectives of the study, or that participation in the studydoes not guarantee the maximum benefit of the subjects.