HPV Vaccination Immune Response Study

Recruiting at 1 trial location

Overseen By Lauren Johnson

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Emory University

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

44 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single center, longitudinal cohort study in which subjects will receive 9-valent HPV vaccine according to package insert (i.e., one dose of 9-valent HPV vaccine on day (D) 0 followed by a second dose 2 months later and a third dose 6 months later). Immune responses in the blood, saliva, bone marrow, and lymph nodes will be assessed in subjects receiving the HPV vaccine. Blood samples for immunologic testing will be collected at screening (from D-60 to D-45), on D0 (before vaccination), D1 (optional visit), D7±1, D14±5, D30±5, D60±5 (Visit 8, before vaccination), Visit 8 +1 day (optional visit), Visit 8 + 7±1 days, Visit 8 + 14±5 days, Visit 8 + 30±5 days, D180±5 (Visit 13, before vaccination), Visit 13 + 7±1 days, Visit 13 + 14±5 days, Visit 13 + 30±5 days, D365±14, D730±14, D1095±14, D1460±14, D1825±30. Saliva samples for antibody testing will be collected on D0 (before vaccination), D30, D60 (before vaccination), Visit 8 + 30±5 days, D180 (before vaccination), Visit 13 + 30±5 days, D365, and D730. Axillary lymph node sampling by fine needle aspiration will be done 3 times per group. Group 1 will have lymph node sampling done D-30 to D0, D14, and D30. Group 2 will have lymph node sampling done D60, Visit 8 + 14±5 days, and Visit 8 + 30±5 days. Group 3 will have lymph node sampling D180, Visit 13 + 14±5 days, and Visit 13 + 30±5 days. Bone marrow sampling will be done for all groups at D730±14 and D1825±30.

Do I need to stop taking my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking anti-coagulant products, anti-platelet products, NSAIDs, or immunosuppressive therapies, you may be excluded from participation. It's best to discuss your specific medications with the trial investigator.

What data supports the idea that HPV Vaccination Immune Response Study is an effective treatment?

The available research shows that the HPV vaccine, including Gardasil 9, is highly effective in preventing infections from the types of HPV that cause most cervical cancers. Gardasil 9 covers more HPV types than earlier versions, increasing protection from about 70% to 90% against cervical cancer-causing strains. Clinical trials have shown that the vaccine is safe and produces a strong immune response, especially in younger age groups. Additionally, Cervarix, another HPV vaccine, has shown high efficacy and long-lasting protection against HPV types 16 and 18, which are responsible for a significant portion of cervical cancers. Both vaccines have excellent safety records and are effective in preventing HPV-related diseases. ^{1 2 3 4 5}

What safety data is available for HPV vaccines?

Safety data for HPV vaccines, including Gardasil, Gardasil 9, and Cervarix, has been extensively studied. Reports from the Vaccine Adverse Event Reporting System (VAERS) and other sources like VigiBase and RIVM indicate that while adverse events have been reported, they are generally not severe. Studies show that Gardasil and Cervarix have comparable safety profiles, with most reactions being mild. Severe adverse events are rare and often unrelated to the vaccine. Overall, these vaccines have an acceptable safety profile based on post-licensure studies and routine use. ^{2 6 7 8 9}

Is Gardasil, the HPV vaccine, a promising drug?

Yes, Gardasil, also known as Gardasil 9, is a promising drug. It protects against nine types of HPV, which can cause cervical cancer. The vaccine has shown to increase protection from about 70% to 90% against these types. It is safe and effective, especially for young people, and is recommended by health organizations worldwide. ^{1 2 3 10 11}

Research Team

Erin Scherer, Ph.D.

Principal Investigator

Emory University

Eligibility Criteria

Adults aged 18-45 with a BMI ≤ 32, in good health, and able to give informed consent can join this HPV vaccine study. They must be willing to undergo lymph node and bone marrow sampling and not have any history of genital warts, abnormal pap smears, positive HPV tests, or certain cancers. Participants should not have received blood products recently or plan major surgery during the study.

Inclusion Criteria

BMI ≤ 32

I am between 18 and 45 years old.

Must be willing to consent to the future use of remaining (residual) samples/specimens

Exclusion Criteria

I have had cancer other than skin cancer, but it was surgically removed and considered cured.

I haven't had, nor plan to have, major surgery within 4 weeks of joining this study.

I have had an organ, bone marrow, or stem cell transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-3 weeks

1 visit (in-person)

Vaccination and Initial Immune Response Assessment

Participants receive the 9-valent HPV vaccine at D0, D60, and D180. Immune responses are assessed through blood, saliva, and lymph node sampling.

6 months

Multiple visits for vaccination and sampling

Extended Immune Monitoring

Participants are monitored for long-term immune responses through blood, saliva, and bone marrow sampling.

5 years

Periodic visits for sampling

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

Treatment Details

Interventions

• Gardasil
• HPV vaccine
• Lidocaine injections

Trial Overview The trial is testing immune responses to the Gardasil HPV vaccine through blood, saliva, bone marrow, and lymph node samples over two years. Participants will receive three doses of the vaccine at specific intervals followed by multiple assessments.

Participant Groups

Group I: Group 3: Lymph node sampling at D180, D194 and D210 Experimental Treatment 2 Interventions

Participants will receive 3 doses of 9-valent HPV vaccine (Gardasil 9) at D0, D60, and D180. Group 3 will undergo an FNA on the same day, but prior to, the third vaccine dose (D180±5; Visit 13) or up to 5 days before. Participants will repeat the procedure at Visit 13 + 14±5 days and Visit 13 + 30±5 days. Bone marrow sampling will be done for all groups at D730 and D1825.

Group II: Group 2: Lymph node sampling at D60, D74 and D90 Experimental Treatment 2 Interventions

Participants will receive 3 doses of 9-valent HPV vaccine (Gardasil 9) at D0, D60, and D180. Participants will undergo an FNA on the same day, but prior to, the second vaccine dose (D60±5; Visit 8) or up to 5 days before. Participants will repeat the procedure at Visit 8 + 14±5 days and Visit 8 + 30±5 days. Bone marrow sampling will be done for all groups at D730 and D1825.

Group III: Group 1: Lymph node sampling at D-30 to D0, D14 and D30 Experimental Treatment 2 Interventions

Participants will receive 3 doses of 9-valent HPV vaccine (Gardasil 9) at D0, D60, and D180. Group 1 will undergo an FNA at D-30 to D0. Participants will repeat the procedure at D14±5 and D30±5. Bone marrow sampling will be done for all groups at D730 and D1825.

Gardasil is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Gardasil 9 for:

• Prevention of cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58
• Prevention of genital warts (condyloma acuminata) caused by HPV types 6 and 11
• Prevention of precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58

Approved in European Union as Gardasil 9 for:

• Prevention of cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58
• Prevention of genital warts (condyloma acuminata) caused by HPV types 6 and 11
• Prevention of precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58

Approved in Canada as Gardasil 9 for:

• Prevention of cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58
• Prevention of genital warts (condyloma acuminata) caused by HPV types 6 and 11
• Prevention of precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58

Approved in Switzerland as Gardasil 9 for:

• Prevention of cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58
• Prevention of genital warts (condyloma acuminata) caused by HPV types 6 and 11
• Prevention of precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Findings from Research

The 9-valent HPV vaccine (Gardasil 9®) significantly increases protection against cervical cancer by covering 9 oncogenic HPV types, raising potential protection from about 70% to 90%, based on clinical trials involving young women.

Clinical trials demonstrated that the 9vHPV vaccine has a comparable safety profile and immunogenicity to the original 4-valent vaccine, with a 2-dose regimen showing similar effectiveness in younger boys and girls compared to the standard 3-dose regimen for older women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded strain coverage for a highly successful public health tool: Prophylactic 9-valent human papillomavirus vaccine. Zhang, Z., Zhang, J., Xia, N., et al.[2019]

A study involving 215,965 individuals who received the nine-valent HPV vaccine (HPV9) found no new safety concerns, confirming its established safety profile from previous research.

While some elevated event categories were noted, such as skin disorders and ill-defined conditions, most were either previously known or had other causes, and no deaths were linked to the vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of 9-valent human papillomavirus vaccine administered to males and females in routine use. Hansen, J., Yee, A., Lewis, N., et al.[2023]

The two-dose HPV vaccine series for pre-adolescent girls (ages 9-15) is effective in providing protection against HPV 16 and other types, with the World Health Organization recommending this schedule since 2015, while older women still require a three-dose series.

Gardasil9 and Cervarix both show strong efficacy in preventing HPV infections, with Cervarix offering a potentially more cost-effective option due to its sustained high antibody levels and the possibility of effective protection with just one dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HPV vaccines - A review of the first decade. Harper, DM., DeMars, LR.[2022]

Both Gardasil and Cervarix HPV vaccines have shown outstanding efficacy in preventing infections and related conditions in young women, with excellent safety profiles and only mild to moderate side effects reported.

Neither vaccine is effective in treating existing HPV infections or lesions, but they provide strong protection against specific HPV types for at least four years, with Gardasil also preventing genital warts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results. Schiller, JT., Castellsagué, X., Villa, LL., et al.[2022]

Cervarix, an HPV vaccine, has shown a 70.2% reduction in cervical precancerous lesions in HPV-naïve young girls, indicating its strong efficacy in preventing cervical cancer caused by HPV types 16, 18, 31, 33, and 45.

Cervarix induces significantly higher levels of neutralizing antibodies and memory immune cells compared to Gardasil, with sustained protection lasting over 7 years, demonstrating its long-term effectiveness and safety in preventing HPV-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical update of the AS04-adjuvanted human papillomavirus-16/18 cervical cancer vaccine, Cervarix. Schwarz, TF.[2020]

Over 4 years of post-licensure safety surveillance of the HPV-16/18 vaccine (Cervarix) showed that the most commonly reported adverse events were consistent with those expected in the general population, indicating a favorable safety profile.

No significant patterns of serious immune-mediated diseases were found, and the incidences of conditions like Bell's palsy and Guillain-Barré syndrome were within expected ranges, reinforcing the vaccine's acceptable benefit-risk profile for adolescent girls and women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-licensure safety surveillance for human papillomavirus-16/18-AS04-adjuvanted vaccine: more than 4 years of experience. Angelo, MG., Zima, J., Tavares Da Silva, F., et al.[2021]

A comprehensive analysis of adverse events (AEs) reported to the Vaccine Adverse Event Reporting System (VAERS) identified 3,112 AEs for Cervarix, 31,606 for Gardasil, and 6,872 for Gardasil 9, highlighting the need for ongoing monitoring of vaccine safety.

The study found 46 unique serious adverse events (SAEs) associated with the HPV vaccines, clustered around behavioral, neurological, immune, nervous, and reproductive systems, indicating that while the vaccines are effective, further research is needed to understand the cause-and-effect relationships of these AEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OAE-based data mining and modeling analysis of adverse events associated with three licensed HPV vaccines. Zi, W., Yang, Q., Su, J., et al.[2022]

The post-licensure safety profile of HPV vaccines Gardasil and Cervarix was evaluated using data from three sources, including VigiBase and VAERS, confirming that the reported adverse events align with existing safety data.

The analysis showed that the safety profiles of both vaccines are consistent with the information provided in their Summary of Product Characteristics (SPC), indicating that they are safe for public use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postlicensure safety evaluation of human papilloma virus vaccines. Labadie, J.[2015]

In a study involving 198 girls aged 12-15, the tetravalent HPV vaccine Gardasil® demonstrated a comparable safety profile to the bivalent HPV vaccine Cervarix®, with most local and systemic reactions being mild and infrequent.

Severe tenderness at the injection site was reported more frequently in the Cervarix® group (24%) compared to the Gardasil® group (7%), indicating that Gardasil® may be associated with fewer injection site reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reactogenicity of Cervarix and Gardasil human papillomavirus (HPV) vaccines in a randomized single blind trial in healthy UK adolescent females. Haskins-Coulter, T., Southern, J., Andrews, N., et al.[2021]

The nine-valent HPV vaccine, Gardasil9, significantly increases the efficacy against cervical cancer from 70% to 90% compared to the quadrivalent vaccine, covering a broader range of HPV types.

Gardasil9 also provides high efficacy (97%) against lesions associated with HPV types 31, 33, 45, 52, and 58, while maintaining similar effectiveness against HPV types 6, 11, 16, and 18 as the quadrivalent vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nine-valent HPV vaccine - new generation of HPV vaccine]. Fait, T., Dvořák, V., Pilka, R.[2018]

Cervarix® induced higher antibody levels and stronger T cell responses compared to Gardasil® after three doses, suggesting it may provide a more robust immune response against HPV-16 and HPV-18.

Both vaccines are highly immunogenic, but the differences in immune responses, such as elevated cytokine levels in Cervarix® recipients, could have clinical implications that require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of adaptive and innate immune responses induced by licensed vaccines for Human Papillomavirus. Herrin, DM., Coates, EE., Costner, PJ., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Expanded strain coverage for a highly successful public health tool: Prophylactic 9-valent human papillomavirus vaccine. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Safety of 9-valent human papillomavirus vaccine administered to males and females in routine use. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

HPV vaccines - A review of the first decade. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Clinical update of the AS04-adjuvanted human papillomavirus-16/18 cervical cancer vaccine, Cervarix. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Post-licensure safety surveillance for human papillomavirus-16/18-AS04-adjuvanted vaccine: more than 4 years of experience. [2021]

7. England pubmed.ncbi.nlm.nih.gov

OAE-based data mining and modeling analysis of adverse events associated with three licensed HPV vaccines. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Postlicensure safety evaluation of human papilloma virus vaccines. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Reactogenicity of Cervarix and Gardasil human papillomavirus (HPV) vaccines in a randomized single blind trial in healthy UK adolescent females. [2021]

10. Czech Republic pubmed.ncbi.nlm.nih.gov

[Nine-valent HPV vaccine - new generation of HPV vaccine]. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Comparison of adaptive and innate immune responses induced by licensed vaccines for Human Papillomavirus. [2018]