Long Term Immune Memory Responses to HPV Vaccination Following 2 vs 3 Doses of Quad-HPV Vaccine

Study Overview
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Brief Summary
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The overall aim of this study is to further understand the memory response to HPV vaccination in subjects who have received 2 versus 3 doses of quadrivalent HPV vaccine. Although memory responses can be detected shortly after immunization, the best approach to measure the long-lasting anamnestic response is to challenge with a booster dose years (> 5) after the original exposure.

Detailed Description
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This is a single center, interventional study to evaluate long term memory response to Q-HPV vaccination and to natural infection. Memory response will be assessed by measuring seroprotection 8-10 years post Q-HPV vaccination and to challenge with a booster dose years after the original exposure to measure the long-lasting anamnestic response.

Official Title
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Long Term Immune Memory Responses to Human Papillomavirus (HPV) Vaccination Following 2 Verses 3 Doses of Quadrivalent HPV Vaccine

Conditions
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Human Papillomavirus

Intervention / Treatment
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* Biological: Human Papillomavirus 9-valent Vaccine, Recombinant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent provided by the participant. Participant whom the investigator believes can and will comply with the requirements of the protocol. General good health. Immunized with Q-HPV vaccine between the ages of 9-13 or 16 to 26 years on the BCGov01 study or the BC provincial program. Participant who is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study. Examples of effective methods of birth control include: Abstinence (no sexual activity) Hormonal contraceptives including oral, injectable, implants & skin patches Intrauterine device (IUD) Male partner sterilization Male condom combined with a vaginal spermicide (foam, gel, film, cream or suppository) Male condom combined with a female diaphragm, whether with or without a vaginal spermicide (foam, gel, cream, or suppository) Adequate contraception does not apply to participants with same sex partners, when this is their preferred and usual lifestyle Exclusion Criteria: Received more than 3 doses of Q-HPV vaccine Received any doses of HPV9 vaccine Systemic hypersensitivity to Q-HPV vaccine or HPV9 vaccine or severe reaction to any previous dose of Q-HPV vaccine. Receipt of blood or blood product within 3 months prior to Visit 1. Receipt of a live vaccine within 28 days or an inactive vaccine within 14 days of Visit 1 Immune compromise resulting from disease or immunosuppressive systemic medication use within 3 months prior to Visit 1. Inadequate participant fluency in English to provide fully informed consent. Participant who is currently pregnant or planning a pregnancy during the course of the trial

Ages Eligible for Study
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Minimum Age: 17 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>Group 1: girls who received 2 doses of Q-HPV vaccine at 0, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study. | Biological: Human Papillomavirus 9-valent Vaccine, Recombinant<br>* All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.<br>* Other names: Gardasil9;|
| Active Comparator: Group 2<br>Group 2: girls who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 9-13 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study. | Biological: Human Papillomavirus 9-valent Vaccine, Recombinant<br>* All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.<br>* Other names: Gardasil9;|
| Active Comparator: Group 3<br>Group 3: young women who received 3 doses of Q-HPV vaccine at 0, 2, 6 month schedule 8-10 years ago when they were between 16-26 years of age at the time of the first dose. The intervention of a single dose of licensed Gardasil 9 vaccine (Human Papillomavirus 9-valent Vaccine, Recombinant) will be administered at Day 0 of the study. | Biological: Human Papillomavirus 9-valent Vaccine, Recombinant<br>* All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.<br>* Other names: Gardasil9;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| B Memory Cell Response (% of Memory B Cells That Are Antigen-specific) | To compare the B memory cell populations between girls that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose after 120 months | At Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine | 
| Plasmablast Response (% of All B Cells That Are Plasmablasts) | To compare the plasmablast populations between girls that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose after 120 months | At Day 7 post challenge dose of Human Papillomavirus 9-Valent vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variable Gene Usage (Comparison of the Nucleotide Sequences of Antigen-specific Antibody Heavy and Light Chain Variable Region Sequences) | To compare the extent of somatic hypermutation and the variable gene usage between girls that received either a primary 2 or 3 dose series | At Day 7 and Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine | 
| Serum Antibody Response (cLIA) - Geometric Mean Titer | To compare the serum antibody responses (cLIA) to HPV 6, 11, 16 & 18 at month 120 in females that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose | At Day 7 post challenge dose of Human Papillomavirus 9-Valent vaccine | 
| Serum Antibody Response (cLIA) - Geometric Mean Titer | To compare the serum antibody responses (cLIA) to HPV 6, 11, 16 & 18 at month 120 in females that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose | At Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine | 
| Serum Antibody Response (Total IgG) - Geometric Mean Titer | To compare the serum antibody responses (total IgG) to HPV 6, 11, 16 & 18 at month 120 in females that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose | At Day 7 post challenge dose of Human Papillomavirus 9-Valent vaccine | 
| Serum Antibody Response (Total IgG) - Geometric Mean Titer | To compare the serum antibody responses (total IgG) to HPV 6, 11, 16 & 18 at month 120 in females that received either a primary 2 or 3 dose series, who are then challenged with a subsequent dose | At Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine |