Long Term Immune Memory Responses to HPV Vaccination Following 2 vs 3 Doses of Quad-HPV Vaccine (Merck08)

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

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.

Study Overview

• Status: Completed
• Conditions: Human Papillomavirus
• Intervention / Treatment: Biological: Human Papillomavirus 9-valent Vaccine, Recombinant

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4H4
      • Vaccine Evaluation Center, BC Children's Hospital Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Biological: 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.; Other Names: Gardasil9
Active Comparator: 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.	Biological: 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.; Other Names: Gardasil9
Active Comparator: 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.	Biological: 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.; Other Names: Gardasil9

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: Merck Canada Inc.
• Investigators: Principal Investigator: Tobi Kollmann, MD PhD, Vaccine Evaluation Center, University of British Columbia; Principal Investigator: Manish Sadarangani, BM BCh DPhil, Vaccine Evaluation Center, University of British Columbia

Publications and helpful links

General Publications

• Olsson SE, Villa LL, Costa RL, Petta CA, Andrade RP, Malm C, Iversen OE, Hoye J, Steinwall M, Riis-Johannessen G, Andersson-Ellstrom A, Elfgren K, von Krogh G, Lehtinen M, Paavonen J, Tamms GM, Giacoletti K, Lupinacci L, Esser MT, Vuocolo SC, Saah AJ, Barr E. Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine. Vaccine. 2007 Jun 21;25(26):4931-9. doi: 10.1016/j.vaccine.2007.03.049. Epub 2007 Apr 20.

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2017
• Primary Completion (Actual): May 15, 2019
• Study Completion (Actual): May 15, 2019

Study Registration Dates

• First Submitted: August 19, 2016
• First Submitted That Met QC Criteria: November 15, 2016
• First Posted (Estimate): November 18, 2016

Study Record Updates

• Last Update Posted (Actual): June 25, 2021
• Last Update Submitted That Met QC Criteria: June 23, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: H16-00700

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: If IPD is required, please contact the study team for further discussions- any sharing will be dependent on alignment with original informed consent obtained from study participants and in agreement with the study team.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No