Evaluating Gardasil HPV Vaccine Humoral and Cellular Immune Responses in People With and Without HIV
- Conditions
- Human Papilloma VirusAnal DysplasiaHIV
- Interventions
- Biological: Human papillomavirus (HPV) vaccine, 9-valent
- Registration Number
- NCT06624839
- Lead Sponsor
- University of Maryland, Baltimore
- Brief Summary
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).
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 120
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description People born male with current or past exposure to androgen blockers or estrogen (BM-EABE) Human papillomavirus (HPV) vaccine, 9-valent One dose of human papillomavirus (HPV) vaccine, 9-valent (Gardasil9) will be administered on Day 0, Month 2, and Month 6 HIV Negative BM-EABE or HIV Negative men who had sex with a person with a penis (MSPP) Human papillomavirus (HPV) vaccine, 9-valent One dose of human papillomavirus (HPV) vaccine, 9-valent (Gardasil9) will be administered on Day 0, Month 2, and Month 6
- Primary Outcome Measures
Name Time Method 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 7 months post 1st vaccine dose 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.
- Secondary Outcome Measures
Name Time Method Compare the humoral immune response to Gardasil9 between HIV positive BM-EABE and HIV negative controls 7 months post 1st vaccine dose The difference between GMT titers against the 9-specific HPV types included in Gardasil between HIV positive BM-EABE and HIV negative controls.
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) 7 months post 1st vaccine dose The difference between GMT titers against the 9-specific HPV types included in Gardasil between BM-EABE and BM without EABE
Evaluate the systemic HPV T-cell immune response to Gardasil9 in HIV positive BM-EABE and HIV negative controls. 7 months post 1st vaccine dose 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).
Compare systemic HPV T-cell immune response to Gardasil9 between HIV positive BM-EABE and HIV negative controls. 7 months post 1st vaccine dose 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
Compare systemic HPV T-cell immune response to Gardasil9 between BM-EABE (regardless of HIV status) and BM without EABE. 7 months post 1st vaccine dose 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.
Evaluate the impact of HPV vaccination on HIV reservoir in CD4 T cells of BM-EABE with HIV. Before vaccination, 7 months post 1st dose 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.
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. 7 months post 1st vaccine dose 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
Trial Locations
- Locations (2)
RIIS Clinic at HIPS
🇺🇸Washington, District of Columbia, United States
RIIS Clinic at Baltimore Safe Haven
🇺🇸Baltimore, Maryland, United States