Study of the Molecular Mechanisms Underlying the Cross-neutralizing Capacity of AS04-adjuvanted HPV Vaccine (Cervarix®) in Comparison With the Aluminiumhydroxyphosphate Sulphate Adjuvanted HPV Vaccine (Gardasil®) (HPVXneutra001)

Six identical female twins aged 9-13 years will participate. One sib of each twin pair will be given Cervarix according to the 0, 1, 6 month vaccination scheme, while the other sib will be given Gardasil according to the 0, 2, 6 month vaccination scheme. Three blood samples will be taken (the first prior to vaccine administration, the second and third 7 days after dose 2 and 3, respectively). The blood samples will be used to determine: 1) the magnitude the anti-HPV 16 and anti-HPV-18 antibody responses, 2) as well as the cross-reactive pattern of these responses towards related, non-vaccine HPV strains (HPV-31 and -33, and HPV-45). 3) plasmablast isolated from blood taken 7 days after the 3rd dose in the first place (and eventually after the 2nd dose also) will be examined for for the usage of VDJ and VJ segments in the immunoglobulin heavy (VH) and light (VL) heavy and light chains. Gene useg in B cells induced by Cervarix and Gardasil will be compared. Finally the cross-reactive potential of monoclonal antibodies obtained by eukaryotic expression of a series of heavy (VH) and light (VL) chains from single ASC isolated after the 3rd dose of a three-dose schedule of either Cervarix or Gardasil will be examined.

The duration of the study is approximately 187 days. Five study visits will take place, over a time period of 6.5 months, followed by a telephone call after 12 months.

The purpose of the study is to learn more about the molecular mechanisms underlying the cross-neutralizing capacity of AS04-adjuvanted HPV vaccine (Cervarix®) in comparison with the aluminiumhydroxyphosphate sulphate adjuvanted HPV vaccine (Gardasil®).

Study Overview

• Status: Completed
• Conditions: Infection With Human Papillomavirus
• Intervention / Treatment: Biological: cervarix; Biological: Gardasil

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Oost-Vlaanderen
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • Ghent University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 13 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Six homozygous twins in good health, without preceding sexual activity (virgin). Subjects have a negative pregnancy test on the day of vaccination and have agreed to continue abstinence during the entire study period and for two months after completion of the vaccination series.

Exclusion Criteria:

• Subjects are not participating in any other clinical trials and have not been vaccinated previously against HPV and have not had an administration of MPL or AS04 in the past.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cervarix group; One sib of each twin pair will be given Cervarix according to the 0, 1, 6 month vaccination scheme.	Biological: cervarix; 3 doses will be given, one on Day 0, one on Day 30 and one on Day 180 ± 7 days, intramuscular in the deltoid muscle of the non-dominant arm; Other Names: GSK's commercially available bivalent HPV types 16 and 18 recombinant vaccine containing AS04 adjuvant (Cervarix®)
Active Comparator: Gardasil Group; One sib of each twin pair will be given Gardasil according to the 0, 1, 6 month vaccination scheme.	Biological: Gardasil; 3 doses will be given, one on Day 0, one on Day 60 ± 2 days and one on Day 180 ± 7 days, intramuscular in the deltoid muscle of the non-dominant arm; Other Names: Merck's commercially availably quadrivalent HPV(types 6, 11, 16, 18) recombinant vaccine containing amorphous aluminiumhydroxyphosphate sulphate adjuvant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
comparing of VDJ and VJ segments in the immunoglobulin heavy and light chains/plasmablasts	at day 187
comparing the mutational diversity that occurs following vaccine-induced affinity maturation in plasmablasts	at day 187

Secondary Outcome Measures

Outcome Measure	Time Frame
evaluation of the cross-reactive pattern of polyclonal serum antibodies	at day 187
comparing of VDJ and VJ segment usage and affinity maturation in HPV-specific antibodies	at day 187
comparing of the cross-reactive potential of monoclonal antibodies obtained by eukaryotic expression of a series of heavy (VH) and light (VL) chains from single ASC	at day 187

Collaborators and Investigators

• Sponsor: University Hospital, Ghent

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2013
• Primary Completion (Actual): September 23, 2015
• Study Completion (Actual): September 23, 2015

Study Registration Dates

• First Submitted: June 6, 2013
• First Submitted That Met QC Criteria: August 1, 2013
• First Posted (Estimate): August 2, 2013

Study Record Updates

• Last Update Posted (Estimate): December 9, 2022
• Last Update Submitted That Met QC Criteria: December 6, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 2013/422; 2013-002340-90 (EudraCT Number)