HPV
Conditions
Keywords
HPV Prevention, HPV Vaccine, Immune responses
Brief summary
This study aims to answer the question: does 1-dose HPV vaccination generate the same immune responses compared to 2- or 3-dose HPV vaccination? This will be done by studying the immune response in blood, lymph nodes, and bone marrow. Human papillomaviruses (HPV) cause cancers (cervical, anal, oropharyngeal, vulvar, vaginal, and penile), and the current HPV vaccine is highly effective at preventing disease by HPV types that cause 90% of cancer cases. While this vaccine generates high levels of antibodies that last for \> 10 years, understanding of how this occurs is limited, and studying this immune response will help design new and better vaccines. The study population consists of healthy adult (age 18-45) participants who have not previously received an HPV vaccine, do not have antibodies against certain types of HPV, do not have a history of HPV infection or disease (such as genital warts, abnormal pap test, or HPV DNA test), and do not have contraindications to study procedures. Populations of increased concern are not being enrolled.
Detailed description
This study aims to determine whether a single-dose HPV vaccination produces the same immune response as a two- or three-dose HPV vaccination. The 1-dose HPV vaccination was recently recommended by the World Health Organization (WHO) for people with healthy immune systems aged 9-20 years. To learn whether 1-dose HPV vaccination makes the same immune responses as 2- or 3-dose HPV vaccination in humans, there is a need to study the immune response to the HPV vaccine in the blood (where antibodies are), in the lymph nodes (where immune cells that make antibodies get activated), and in the bone marrow (where long-lived cells that produce antibodies are found). After informed consent, participants will have blood drawn for screening tests. If they are eligible, they will receive the FDA-approved HPV vaccine. The vaccine will be given in 1 or 2 doses, but participants will have the opportunity to receive the full vaccine series at the end of the study. Participants will have additional blood draws and undergo fine needle aspiration (FNA) of a lymph node in the axilla (armpit) at 3 different times. Later, they will have bone marrow aspiration procedures during which marrow is sampled from the hip bone through a needle. Researchers will use this knowledge to inform public health decisions about the broader use of 1-dose HPV vaccination.
Interventions
BIOLOGICALGardasil-9
The 9-valent HPV VLP vaccine is a sterile liquid suspension prepared by combining the adsorbed VLPs of each HPV type and additional amounts of the aluminum-containing adjuvant and the final purification buffer. The 9-valent HPV vaccine, or Gardasil-9, is a sterile suspension for intramuscular administration. Each 0.5-mL dose of the vaccine also contains approximately 500 mcg of aluminum (provided as AAHS), 9.56 mg of sodium chloride, 0.78 mg of L-histidine, 50 mcg of polysorbate 80, 35 mcg of sodium borate, \<7 mcg yeast protein, and water for injection. The product does not contain a preservative or antibiotics. Gardasil-9 is supplied as a 0.5-mL single-dose vial or 0.5-mL single-dose prefilled Luer Lock syringe with tip cap. After thorough agitation, GARDASIL 9 is a white, cloudy liquid.
Lidocaine 1% will be injected intradermally and subcutaneously into the margin of the lymph node to be sampled to numb the area. To confer local anesthesia, 1-2% will be injected into the tissue surrounding the area where the bone marrow will be removed.
DRUGLorazepam
Lorazepam, an FDA-approved benzodiazepine, will be administered as an anxiolytic before the bone marrow aspirate procedure per the clinician who will perform the procedure. If needed, lorazepam will be administered sublingually per manufacturer dosing recommendations.
Sponsors
Merck Sharp & Dohme LLC
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Individuals aged 18-45 years old (inclusive), as the HPV vaccine is approved for this age range in adults * BMI ≤ 32 * Able to understand and give informed consent (in American English). * In good health based on physical examination, vital signs, medical history, and the investigator's clinical judgment. * Available and willing to participate for the duration of this study * Willing to undergo lymph node fine needle aspiration and bone marrow aspiration * Willing to consent to the future use of remaining (residual) samples/specimens with IRB review * Willing to defer completion of the recommended 9vHPV series
Exclusion criteria
* Ever received a dose of an HPV vaccine * HPV 6, 11, 16, 18, 31, 33, 45, 52 or 58 seropositivity * Any history of genital warts, an abnormal pap smear, or positive HPV DNA test * Known allergy or history of anaphylaxis or other serious adverse reaction to a vaccine or vaccine products * Known allergy or history of anaphylaxis to yeast or products containing yeast. * Any allergy to lidocaine. * Pregnancy or breastfeeding. * Participants who believe they cannot tolerate the lymph node fine needle aspirate or bone marrow aspirate procedures without general sedation * Any history of lymphoma involving axillary nodes, any history of breast cancer, bilateral inflammatory process of upper arms in the past 2 weeks, prior breast or axillary biopsy and/or surgery that in the opinion of the investigator would affect the immune response results. * Local infection, lymphadenitis, or rash in the targeted area. * Received any vaccine from 14 days before the vaccine dose until 30 days after each vaccine dose\* (\*An individual initially excluded from study participation based on one or more of the time-limited
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of plasma cells specific for HPV16/18 virus like particles (VLPs) | 730 days after receiving the first vaccine dose | Frequency of plasma cells specific for HPV16/18 virus-like particles (VLPs) per total IgG-secreting plasma cells in bone marrow in per-protocol participants of the 1- and 2-dose 9vHPV arms |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of memory B cells specific for HPV16/18 VLPs | Baseline (Day 0), Day 30, Day 180, Day 210, Day 365, and Day 730 post-intervention | Frequency of memory B cells specific for HPV16/18 VLPs per total memory B cells in PBMC in per protocol participants of the 1- and 2-dose 9vHPV arms. |
Countries
United States
Contacts
Primary ContactErin Scherer, PhD
Backup ContactDaniel Graciaa, MD
Outcome results
None listed