Immunogenicity of HPV Vaccine in Transplant Recipients.

Study Overview
=================
Brief Summary
-----------------
To measure levels of HPV antibodies in pre-renal organ transplant and renal transplant recipients who have gotten the HPV9 vaccine and compare to control antibody levels.

Detailed Description
-----------------
This is a prospective open-label nonrandomized single-center cohort study aimed to analyze the immunogenicity of nanovalent human papillomavirus vaccination (GARDASIL 9) in patients pre and post solid organ transplant. The study duration is anticipated to be 36 months. The expected duration of subject participation is 24 months. Immunocompromised populations are at greater risk of HPV infection. Quadrivalent HPV vaccination has been performed and lower titers of antibodies have been compared to published date in non-immunocompromised population (controls). The HPV9 vaccination titers have not been measured in the immunocompromised population to date. Group 1 (50 patients): Adult patients listed for renal transplant ages 18-45 will be enrolled in the outpatient transplant and nephrology clinic at the Medical College of Wisconsin - Froedtert Memorial Lutheran Hospital. Group 2: (50 patients): Adult renal transplant recipients ages 18 -45 years > 6 months from transplant will be candidates for participation in the outpatient transplant and nephrology clinics at the Medical College of Wisconsin - Froedtert Memorial Lutheran Hospital. Patients will be scheduled to receive 3-dose 9vHPV vaccination (vaccination at enrollment [time 0], 2 months [+ 6 weeks], and 6 months [+ 6 weeks] per standard guidelines) prior to renal transplantation for one cohort (Group 1) and after renal transplant in the second cohort (Group 2). Serial serum samples will be obtained for geometric mean titers (GMT) prior to vaccination, at 7 months (+ 6 weeks), 12 months (+ 6 weeks), and 24 months (+ 6 weeks) after completion of the vaccination series. If a patient is subsequently scheduled to undergo a transplant, we will obtain the GMT prior to the transplant. Subjects will be asked to consent to optional banking of whole-blood for future research and translational studies. Blood will be stored in the Obstetrics & Gynecology Specimen and Data Bank (PRO 11631) at Medical College of Wisconsin. If subjects chose to participate in the optional banking of their blood, approximately 5 mls of additional blood will be drawn prior to vaccination and at the time of the 7, 12, and 24- month GMT blood draws. Anti-HPV antibody responses will be measured using a proprietary MERCK Competitive Luminex Immunoassay (cLIA) which will be performed by Merck and expressed as geometric mean titers (GMT).

Official Title
-----------------
Prospective Analysis of Immunogenicity of the Nonavalent Human Papillomavirus Vaccination (GARDASIL 9) in Patients Pre and Post Solid Organ Transplant

Conditions
-----------------
Chronic Kidney Diseases, Kidney Transplant

Intervention / Treatment
-----------------
* Biological: Human Papilloma Virus vaccine (GARDASIL 9)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: male and female patients between the ages of 18 and 45 years with chronic kidney disease who are on the kidney transplant waiting list and have not received GARDASIL 9. male and female patients between the ages of 18 and 45 years who are at least 6 months post kidney transplant and have not received GARDASIL 9. Subjects can participate in their health care and sign informed consent. Subjects may have had bivalent or quadrivalent HPV vaccination previously. Both living and deceased donor transplant patients are eligible. Exclusion Criteria: Contraindication: Hypersensitivity, including severe allergic reactions to yeast (a vaccine component), or after a previous dose of GARDASIL 9 or GARDASIL. Prior to GARDASIL 9 vaccination completion. Subjects that are pretransplant and taking immunosuppressive medication. Subjects listed for or having more than one organ transplant. Subjects that are planned for kidney re-transplantation. Subjects with a diagnosis of HIV. Subjects that endorse being currently pregnant.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1<br>Patients prior to renal transplant: 9vHPV 0,2,6 months. Immunogenicity test on 0, 7, 12, 24 months. | Biological: Human Papilloma Virus vaccine (GARDASIL 9)<br>* Patients will be scheduled to receive 3-dose 9vHPV vaccination (vaccination at enrollment [time 0], 2 months [+ 6 weeks], and 6 months [+ 6 weeks] per standard guidelines) prior to renal transplantation for one cohort (Group 1) and after renal transplant in the second cohort (Group 2).<br>|
| Group 2<br>Patients > 6 months from renal transplant: 9vHPV 0,2,6 months. Immunogenicity test on 0, 7, 12, 24 months. | Biological: Human Papilloma Virus vaccine (GARDASIL 9)<br>* Patients will be scheduled to receive 3-dose 9vHPV vaccination (vaccination at enrollment [time 0], 2 months [+ 6 weeks], and 6 months [+ 6 weeks] per standard guidelines) prior to renal transplantation for one cohort (Group 1) and after renal transplant in the second cohort (Group 2).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Outcome | The primary outcome is to measure immunogenicity using the Merck proprietary Competitive Luminex Immunoassay (cLIA) and geometric mean titers (GMTs) over specified time intervals (7 months, 12 months and 24 months from vaccination) in a patient cohort prior to kidney transplant (Group 1) and in a patient cohort after kidney transplant (Group 2) to each of the nine human papillomavirus types contained in the nanovalent human papillomavirus vaccine (HPV9) vaccination and compare these antibody levels to published control data for non-immunocompromised individuals. this has been completed previously for the quadrivalent HPV vaccination series but no data exists for the HPV9 vaccination in this population. We will also compare GMTs between the two groups in our study and over time to determine if there is a difference between timing of vaccine administration. | 7 months, 12 months and 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Outcome | Immunogenicity using the Merck proprietary Competitive Luminex Immunoassay (cLIA) and geometric mean titers (GMTs) over specified time intervals (7 months, 12 months and 24 months from vaccination) in a patient cohort prior to kidney. We will assess the change in GMT over time. The utilization of regression analysis to determine the effect of variables on antibody response (GMTs) such as age, gender, race, renal function and type of immunosuppression, and donor type. | 7 months, 12 months and 24 months |