Evaluating Gardasil HPV Vaccine Humoral and Cellular Immune Responses in People With and Without HIV (PROTECT)

A PRe-pOsT Interventional Study Evaluating Gardasil Nine-valent Human Papilloma Virus (HPV) Vaccine Humoral and Cellular Immune Responses in People With or Without HIV

This is a phase 2, open-label study to assess the immunogenicity of the 9-valent human papillomavirus (HPV) recombinant vaccine (Gardasil9) in people born male with current or past exposure to androgen blockers or estrogen (BM-EABE). Investigators will enroll BM-EABE with HIV and HIV negative controls (BM-EABE or men who have sex with a person with a penis (MSPP)) and administer Gardasil9 at timepoints Day 0, Month 2, and Month 6. The immune response to the vaccine will be analyzed at Month 7 (1 month following the final vaccine dose).

Study Overview

• Status: Recruiting
• Conditions: HIV; Human Papilloma Virus; Anal Dysplasia
• Intervention / Treatment: Biological: Human papillomavirus (HPV) vaccine, 9-valent

Detailed Description

This will be a phase 2, open-label study to assess the humoral and cellular immune response to the FDA-approved 9-valent HPV recombinant vaccine in people born male with current or past exposure to androgen blockers or estrogen (BM-EABE). At baseline, BM-EABE with HIV, HIV negative controls (BM-EABE or men who have sex with a person with a penis (MSPP)) will provide blood samples and anal swabs for evaluation of HPV immunity, anal HPV and anal dysplasia. All participants will undergo a 3-dose vaccine series of the Gardasil vaccine (at Day 0, Month 2 and Month 6). Participants will then return one month after completion of third vaccine (Month 7) to provide repeat blood samples and anal swabs. Samples will be compared pre and post vaccination and in-between participants based on HIV and exposure to androgen blockers or estrogen (EABE).

Any participant with human papillomavirus 16 (HPV16) and/or anal dysplasia on anal cytology at any point will be referred to high-resolution anoscopy (HRA) for clinical management. Anal biopsies will be procured from different pathology laboratories - after clinical evaluation has been complete - for research analysis, including confocal microscopy. Those who had anal dysplasia at study entry will undergo repeat HRA, as clinically indicated, and will have an optional study visit following their repeat HRA to provide blood draw and anal swabs.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Omar Harfouch, MD; Phone Number: 410-706-1372; Email: oharfouch@ihv.umaryland.edu
• Study Contact Backup: Name: Onyinyechi Ogbumbadiugha-Weekes, MPH; Phone Number: 443-635-4943; Email: oogbumbadiugha@ihv.umaryland.edu

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20002
      • Not yet recruiting
      • RIIS Clinic at HIPS
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • RIIS Clinic at Baltimore Safe Haven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 18 years old or older and 70 years old or younger
• Able to provide informed consent
• Denies history of prior HPV vaccination with Gardasil9 (receipt of HPV vaccination other than Gardasil9 such as the bivalent or the quadrivalent HPV vaccine will be allowed) or unsure of vaccination status and born before 2003
• Born Male

For Test group: HIV-positive people born male with current or past exposure to androgen blockers or estrogen (BM-EABE)

• Living with HIV
• Current or past exposure to androgen blockers or estradiol

For Control group: HIV-negative Control

• HIV negative
• Either: Current or past exposure to androgen blockers or estradiol; no current or past exposure to androgen blockers or estradiol AND had sex with a person with a penis in the last year

Exclusion Criteria:

• Younger than 18 years old or older than 70 years old.
• Self-reported or documented history of nine-valent HPV vaccine or unsure of vaccination status and born after 2003.
• Born female
• History of hypersensitivity, including severe reactions to yeast or other component of the vaccine.
• Any condition requiring systemic chemotherapy or immunomodulant affecting antibody responses (i.e., rituximab, ibrutinib etc.), intravenous or subcutaneous immunoglobulin supplementation, radiation therapy, or immunomodulatory treatment within the previous 6 months (presence of precancerous lesions is not exclusionary).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: People born male with current or past exposure to androgen blockers or estrogen (BM-EABE); One dose of human papillomavirus (HPV) vaccine, 9-valent (Gardasil9) will be administered on Day 0, Month 2, and Month 6	Biological: Human papillomavirus (HPV) vaccine, 9-valent; 0.5 ml intramuscular injection; Other Names: Gardasil9
Active Comparator: HIV Negative BM-EABE or HIV Negative men who had sex with a person with a penis (MSPP); One dose of human papillomavirus (HPV) vaccine, 9-valent (Gardasil9) will be administered on Day 0, Month 2, and Month 6	Biological: Human papillomavirus (HPV) vaccine, 9-valent; 0.5 ml intramuscular injection; Other Names: Gardasil9

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity of the human papillomavirus (HPV) vaccine in BM-EABE (people born male with current or past exposure to androgen blockers or estrogen (BM-EABE) with and without HIV	Proportion of BM-EABE who become seropositive or have an increase in their GMT by >25% to at least 1 homologous HPV vaccine genotype at 1 month following the 3rd dose of the vaccine.	7 months post 1st vaccine dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the humoral immune response to Gardasil9 between HIV positive BM-EABE and HIV negative controls	The difference between GMT titers against the 9-specific HPV types included in Gardasil between HIV positive BM-EABE and HIV negative controls.	7 months post 1st vaccine dose
Compare the humoral immune response to Gardasil9 between BM-EABE (regardless of HIV status) and BM without EABE (people born male without current or past exposure to androgen blockers or estrogen)	The difference between GMT titers against the 9-specific HPV types included in Gardasil between BM-EABE and BM without EABE	7 months post 1st vaccine dose
Evaluate the systemic HPV T-cell immune response to Gardasil9 in HIV positive BM-EABE and HIV negative controls.	A comprehensive assessment of HPV-specific T cell responses will be conducted with antigen stimulation of peripheral blood mononuclear cells (PBMCs) with virion-like protein (VLP) included in Gardasil 9. The proportion of proliferating T- cells, expressing activation-induced markers (AIM+) and IFN-gamma and TNF-alpha secreting T-cells will be evaluated by flow-cytometric assays; in addition the expression of exhaustion markers, perforin/granzyme B and skin- and gut-homing receptors, as well as the transcriptional analysis of T cells proliferating upon HPV antigenic stimulation will be assessed. This response will be assessed in HIV positive BM-EABE and HIV negative controls (BM-EABE and BM without EABE).	7 months post 1st vaccine dose
Compare systemic HPV T-cell immune response to Gardasil9 between HIV positive BM-EABE and HIV negative controls.	The proportion of proliferating T- cells, expressing activation-induced markers (AIM+) and IFN-gamma and TNF-alpha secreting T-cells, the expression of exhaustion markers, perforin/granzyme B and skin- and gut-homing receptors and the transcriptional analysis of T cells proliferating upon HPV antigenic stimulation will be compared between: HIV positive BM-EABE and HIV negative controls; BM-EABE and BM without EABE	7 months post 1st vaccine dose
Compare systemic HPV T-cell immune response to Gardasil9 between BM-EABE (regardless of HIV status) and BM without EABE.	The proportion of proliferating T- cells, expressing activation-induced markers (AIM+) and IFN-gamma and TNF-alpha secreting T-cells, the expression of exhaustion markers, perforin/granzyme B and skin- and gut-homing receptors and the transcriptional analysis of T cells proliferating upon HPV antigenic stimulation will be compared in BM-EABE and BM without EABE.	7 months post 1st vaccine dose
Evaluate the impact of HPV vaccination on HIV reservoir in CD4 T cells of BM-EABE with HIV.	Distribution and density of mucosal immune cells (CD4+ and CD8+ T-cells, B/plasma cells, Dendritic/Langerhans cells, Natural killer (NK) cells, and macrophages) as seen on confocal microscopy from anal biopsies from HIV positive BM-EABE and HIV negative controls before Gardasil vaccination. Difference in distribution of mucosal immune cells as seen on confocal microscopy from anal biopsies after Gardasil.	Before vaccination, 7 months post 1st dose
Compare humoral immune response to Gardasil9 between different subset populations from PROTECT (HIV positive BM-EABE , HIV negative BM-EABE , and HIV negative MSPP), to age-matched historical controls.	The difference between GMT titers against the 9-specific HPV types included in Gardasil between subset of populations from PROTECT (HIV positive BM-EABE, HIV negative BM-EABE, men who have sex with a person with a penis (MSPP)) and historical controls from stored samples at the NIH	7 months post 1st vaccine dose

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Investigators: Principal Investigator: Omar Harfouch, MD, University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: July 30, 2024
• First Submitted That Met QC Criteria: September 30, 2024
• First Posted (Actual): October 3, 2024

Study Record Updates

• Last Update Posted (Actual): May 4, 2025
• Last Update Submitted That Met QC Criteria: April 30, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Papilloma
• Other Study ID Numbers: HP-00109701

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The principal investigator will share de-identified data with approved researchers at the time of publication or shortly afterwards.
• IPD Sharing Time Frame: Data will be made available at the time of publication or shortly following publication, and will be available indefinitely.
• IPD Sharing Access Criteria: The criteria will be determined by the Principal Investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes