Human Papillomavirus
Conditions
Brief summary
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
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.
Interventions
All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study.
Sponsors
Merck Canada Inc.
University of British Columbia
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
17 Years to 35 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| B Memory Cell Response (% of Memory B Cells That Are Antigen-specific) | At Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine | 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 |
| Plasmablast Response (% of All B Cells That Are Plasmablasts) | At Day 7 post challenge dose of Human Papillomavirus 9-Valent vaccine | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Variable Gene Usage (Comparison of the Nucleotide Sequences of Antigen-specific Antibody Heavy and Light Chain Variable Region Sequences) | At Day 7 and Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine | To compare the extent of somatic hypermutation and the variable gene usage between girls that received either a primary 2 or 3 dose series |
| Serum Antibody Response (cLIA) - Geometric Mean Titer | At Day 7 post challenge dose of Human Papillomavirus 9-Valent vaccine | 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 |
| Serum Antibody Response (Total IgG) - Geometric Mean Titer | At Day 7 post challenge dose of Human Papillomavirus 9-Valent vaccine | 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 |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 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.
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study. | 6 |
| Group 2 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.
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study. | 6 |
| Group 3 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.
Human Papillomavirus 9-valent Vaccine, Recombinant: All groups will receive a single dose of the Gardasil9 vaccine at Visit 1/Day 0 of the study. | 6 |
| Total | 18 |
Baseline characteristics
| Characteristic | Group 1 | Group 2 | Group 3 | Total |
|---|---|---|---|---|
| Age, Continuous | 22.05 years STANDARD_DEVIATION 0.89 | 21.95 years STANDARD_DEVIATION 1.66 | 30.02 years STANDARD_DEVIATION 3.34 | 24.67 years STANDARD_DEVIATION 4.41 |
| BMI | 27.37 Kg/m^2 STANDARD_DEVIATION 6.69 | 24.23 Kg/m^2 STANDARD_DEVIATION 6.15 | 25.63 Kg/m^2 STANDARD_DEVIATION 3.42 | 25.74 Kg/m^2 STANDARD_DEVIATION 5.42 |
| Race/Ethnicity, Customized Chinese | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other/mixed | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 5 Participants | 4 Participants | 13 Participants |
| Region of Enrollment Canada | 6 participants | 6 participants | 6 participants | 18 participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 6 Participants | 18 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Weight | 74.60 kg STANDARD_DEVIATION 18.03 | 72.25 kg STANDARD_DEVIATION 26.51 | 73.75 kg STANDARD_DEVIATION 15.4 | 73.53 kg STANDARD_DEVIATION 19.31 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 0 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
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
Time frame: At Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 | B Memory Cell Response (% of Memory B Cells That Are Antigen-specific) | HPV16 | 0.61 % of memory B cells that are Ag-specific | Standard Deviation 0.49 |
| Group 1 | B Memory Cell Response (% of Memory B Cells That Are Antigen-specific) | HPV18 | 0.08 % of memory B cells that are Ag-specific | Standard Deviation 0.18 |
| Group 2 | B Memory Cell Response (% of Memory B Cells That Are Antigen-specific) | HPV16 | 0.94 % of memory B cells that are Ag-specific | Standard Deviation 0.94 |
| Group 2 | B Memory Cell Response (% of Memory B Cells That Are Antigen-specific) | HPV18 | 0.11 % of memory B cells that are Ag-specific | Standard Deviation 0.13 |
| Group 3 | B Memory Cell Response (% of Memory B Cells That Are Antigen-specific) | HPV16 | 0.36 % of memory B cells that are Ag-specific | Standard Deviation 0.23 |
| Group 3 | B Memory Cell Response (% of Memory B Cells That Are Antigen-specific) | HPV18 | 0.03 % of memory B cells that are Ag-specific | Standard Deviation 0.05 |
Primary
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
Time frame: At Day 7 post challenge dose of Human Papillomavirus 9-Valent vaccine
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 | Plasmablast Response (% of All B Cells That Are Plasmablasts) | 2.37 % of all B cells that are plasmablasts | Standard Deviation 2.51 |
| Group 2 | Plasmablast Response (% of All B Cells That Are Plasmablasts) | 3.14 % of all B cells that are plasmablasts | Standard Deviation 3.53 |
| Group 3 | Plasmablast Response (% of All B Cells That Are Plasmablasts) | 5.37 % of all B cells that are plasmablasts | Standard Deviation 6.46 |
Secondary
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
Time frame: At Day 7 post challenge dose of Human Papillomavirus 9-Valent vaccine
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group 1 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV6 | 338 antibody titer |
| Group 1 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV11 | 1277 antibody titer |
| Group 1 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV16 | 4922 antibody titer |
| Group 1 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV18 | 855 antibody titer |
| Group 2 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV18 | 2140 antibody titer |
| Group 2 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV6 | 1864 antibody titer |
| Group 2 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV16 | 15237 antibody titer |
| Group 2 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV11 | 5071 antibody titer |
| Group 3 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV18 | 807 antibody titer |
| Group 3 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV11 | 3807 antibody titer |
| Group 3 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV16 | 10122 antibody titer |
| Group 3 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV6 | 699 antibody titer |
Secondary
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
Time frame: At Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group 1 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV6 | 1313 antibody titer |
| Group 1 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV11 | 3430 antibody titer |
| Group 1 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV16 | 21135 antibody titer |
| Group 1 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV18 | 3326 antibody titer |
| Group 2 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV18 | 2615 antibody titer |
| Group 2 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV6 | 2722 antibody titer |
| Group 2 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV16 | 21768 antibody titer |
| Group 2 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV11 | 6042 antibody titer |
| Group 3 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV18 | 1312 antibody titer |
| Group 3 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV11 | 5778 antibody titer |
| Group 3 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV16 | 18930 antibody titer |
| Group 3 | Serum Antibody Response (cLIA) - Geometric Mean Titer | HPV6 | 815 antibody titer |
Secondary
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
Time frame: At Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group 1 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV6 | 4579 antibody titer |
| Group 1 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV11 | 3234 antibody titer |
| Group 1 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV16 | 25808 antibody titer |
| Group 1 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV18 | 6363 antibody titer |
| Group 2 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV18 | 4985 antibody titer |
| Group 2 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV6 | 7308 antibody titer |
| Group 2 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV16 | 32051 antibody titer |
| Group 2 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV11 | 6637 antibody titer |
| Group 3 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV18 | 1813 antibody titer |
| Group 3 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV11 | 6271 antibody titer |
| Group 3 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV16 | 12364 antibody titer |
| Group 3 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV6 | 7371 antibody titer |
Secondary
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
Time frame: At Day 7 post challenge dose of Human Papillomavirus 9-Valent vaccine
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group 1 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV6 | 1263 antibody titer |
| Group 1 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV11 | 1009 antibody titer |
| Group 1 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV16 | 4715 antibody titer |
| Group 1 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV18 | 1418 antibody titer |
| Group 2 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV18 | 3694 antibody titer |
| Group 2 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV6 | 6079 antibody titer |
| Group 2 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV16 | 10962 antibody titer |
| Group 2 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV11 | 5184 antibody titer |
| Group 3 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV18 | 946 antibody titer |
| Group 3 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV11 | 3371 antibody titer |
| Group 3 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV16 | 7607 antibody titer |
| Group 3 | Serum Antibody Response (Total IgG) - Geometric Mean Titer | HPV6 | 3712 antibody titer |
Secondary
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
Time frame: At Day 7 and Day 30 post challenge dose of Human Papillomavirus 9-Valent vaccine
Population: The extent of somatic hypermutation was planned by comparing the nucleotide sequences of the heavy and light chain variable region sequences of each antibody cloned in this study to germ line sequences of these genes in public databases. This was not possible due to insufficient quality of DNA for sequencing.