Safety, Tolerability and Immunogenicity of a Nine-valent Human Papillomavirus (HPV) Vaccine in HIV and Transplant Patients

Inclusion Criteria:

1. Independent Ethics Committee (IEC)-approved written informed consent form (ICF) mustbe obtained from the subject prior to any study-related procedure (includingdiscontinuation of prohibited medication, if applicable) as required by local law.

2. Subject (man or woman) is between the age of 18 years and 0 days and 45 years and 365days for HIV patients, between 18 years and 0 days and 55 years and 365 days fortransplant patients at time of signing the ICF.

3. Subject is able to understand and adhere to the study procedures (e.g., is notplanning to relocate far from the investigational centre during the study period); isable to read, understand, and complete the vaccination diary; is able to understandthe risks involved with the study; and voluntarily agrees to participate in the studyby giving written informed consent.

4. • Since the first day of their last menstrual period through Day 1, female subjectshave not had sex with males or has had sex with males and used effective contraceptionwith no failures (an example of a failure is a male condom that ruptures during sexualintercourse). Effective contraception is defined as a marketed, approved contraceptiveproduct that the subject has used per the manufacturer's instructions with every actof sexual intercourse. The subject understands and agrees that during the Day 1through Month 7 period, she should not have sexual intercourse with males withouteffective contraception. The use of the rhythm method alone, withdrawal alone, andemergency contraception, are not acceptable methods per the protocol. Subjects whohave reached menopause, undergone hysterectomy, bilateral oophorectomy, or bilateraltubal ligation are eligible without the use of contraceptives. Postmenopausal statusis defined as: (1) No menses for >1 year but <3 years and confirmed by folliclestimulating hormone (FSH) levels elevated into the postmenopausal range, or (2) nomenses for at least 3 years.
5. • Subject has had no temperature ≥37.8°C within 24 hours prior to the first injection.

6. Patient considerations

• HIV patients: have CD4+ T cell count of >200 cells/mm² at the last control (lessthan 16 months ago).

• SOT patients received their organ transplantation ≥12 months prior to vaccinationand has been stable in the past 6 months (i.e. no acute rejection or otherimmunological reactions).

7. Apart from having HIV or received a solid organ transplant, the subject is in stablecondition (i.e. no graft-versus-host disease or other immunological reactions) and isjudged to be in good physical health on the basis of medical history, physicalexamination (if deemed necessary), and laboratory testing

8. Subject agrees to provide study personnel with a primary telephone number as well asan alternate telephone number for follow-up purposes.

Exclusion Criteria:

1. Subject has a history of an abnormal Pap test or abnormal cervical biopsy results (showing cervical intraepithelial neoplasia or worse) or cervical disease (i.e.,surgical treatment for cervical lesions).

2. Patient medical history regarding HPV lesions:

3. Exclusion criterion for HIV patients: Subject has history of high grade AnalIntraepithelial Neoplasia, high grade Vulvar Intraepithelial Neoplasia or highgrade Vaginal Intraepithelial Neoplasia.

• history of anal or peri-anal condyloma is allowed

2. Exclusion criterion for SOT patients: Subject has history genital warts, AnalIntraepithelial Neoplasia, Vulvar Intraepithelial Neoplasia or VaginalIntraepithelial Neoplasia.

3. Subject has a history of known prior vaccination with an HPV vaccine, i.e., received amarketed HPV vaccine, or has participated in an HPV vaccine clinical study and hasreceived either active agent or placebo.

4. Subject is pregnant (as determined by serum or urine pregnancy test).

5. Subject is, at the time of signing ICF, a user of recreational or illicit drugs or hashad a recent history (within the last year) of drug or alcohol abuse or dependence.Alcohol abusers are defined as those who drink despite recurrent social,interpersonal, and/or legal problems as a result of alcohol use.

6. Subject has a history of severe allergic reaction, including known allergy to anyvaccine component, including aluminum, yeast, or BENZONASE® (nuclease, Nycomed [usedto remove residual nucleic acids from this and other vaccines]) (e.g., swelling of themouth and throat, difficulty breathing, hypotension or shock) that met the criteriafor serious adverse experiences defined in this protocol.

7. Patient's condition

8. Exclusion criterion only for HIV patients: Subject has had a splenectomy, or hasbeen diagnosed as having a congenital immunodeficiency, lymphoma, leukaemia,systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoidarthritis, inflammatory bowel disease, or other autoimmune or immunosuppressivecondition, or has a history of any disease, which, in the investigator's opinion,may confound the results of the study or pose an additional risk to the subject.

9. Exclusion criterion only for SOT patients: Subject has had a splenectomy, or hasbeen diagnosed as having a congenital or acquired immunodeficiency, HIVinfection, lymphoma, leukaemia, systemic lupus erythematosus, rheumatoidarthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, or otherautoimmune or immunosuppressive condition, or has a history of any disease,which, in the investigator's opinion, may confound the results of the study orpose an additional risk to the subject.

10. Patient's medication

11. Exclusion criterion only for HIV patients: Subject is receiving or has receivedin the year prior to enrolment the following immunosuppressive therapies:radiation therapy, cyclophosphamide, azathioprine, methotrexate, anychemotherapy, cyclosporin, leflunomide (tumour necrosis factor-α antagonists,monoclonal antibody therapies (including rituximab [Rituxan]), intravenous gammaglobulin, antilymphocyte sera, or other therapy known to interfere with theimmune response. With regard to systemic corticosteroids, a subject will beexcluded if she is currently receiving steroid therapy, has recently (defined aswithin 2 weeks of enrolment) received such therapy, or has received 2 or morecourses of high dose corticosteroids (≥20mg/day of prednisone [or equivalent]orally or parenterally) lasting at least 1 week in duration in the year prior toenrolment. Subjects using inhaled, nasal, or topical corticosteroids areconsidered eligible for the study

12. Exclusion criterion only for SOT patients: Subject is receiving or has receivedin the year prior to enrolment the following immunosuppressive therapies:radiation therapy, cyclophosphamide, methotrexate, any chemotherapy, leflunomide (tumour necrosis factor-α antagonists, monoclonal antibody therapies (includingrituximab [Rituxan]) ,intravenous gamma globulin or antilymphocyte sera.

13. Subject has received any immune globulin or blood-derived product within the 3 monthsprior to the Day 1 vaccination, or plans to receive any such product during Day 1through Month 7 of the study.

14. Subject has thrombocytopenia or other coagulation disorder that would contraindicateintramuscular injections.

15. • Subject has received inactivated vaccines within 14 days prior to the Day 1vaccination or has received replicating (live) vaccines within 28 days prior to theDay 1 vaccination. The administration of the inactivated influenza vaccine is allowed 7 days prior to or after each study vaccine.

16. Subject is concurrently enrolled in a clinical study of investigational agent.

17. Subject has a history or current condition of which the investigator believes that itmight interfere with the study vaccines.

18. Subject has a history or current evidence of any condition, therapy, lab abnormalityor other circumstance that might confound the results of the study, or interfere withthe subject's participation for the full duration of the study, such that it is not inthe best interest of the subject to participate.

19. Subject is or has an immediate family member (e.g., spouse, parent/legal guardian,sibling or child) who is investigational site or Sponsor staff directly involved withthis trial