Cervical cancer MedDRA version: 14.1 Level: LLT Classification code 10071147 Term: Human papilloma virus immunization System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
Trade Name: Cervarix
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Human Papillomavirus Type 16 L1 protein and Human Papillomavirus Type 18 L1 protein adjuvanted by ASO4 adsorbed
Sponsors
Department off Infectious Diseases, Aarhus University Hospital Skejby, Denmark
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria Transplant candidates: • Signed Written Informed Consent. • Men and women aged 18-70 at inclusion • Chronic renal failure with estimated GRF (e-GFR=65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: • Pregnancy (positive pregnancy test) • Nursing women • Women of childbearing potential, unwilling to use effective contraception throughout the study • History of hypersensitivity to vaccines • Known allergy to one or more of the vaccine components • Any medical, psychiatric and/or social reason including alcohol/drug abuse which in the opinion of the investigator, renders the candidate inappropriate for participation in the study • Previously received a human papilloma virus vaccine. • Active cancer disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective is to analyze and compare the immune response to bivalent human papilloma virus (HPV) and quadrivalent HPV vaccine among kidney transplant candidates and recipients. Specific main objective: To compare immunogenicity and safety of bivalent and quadrivalent HPV vaccine. The main hypothesis is that bivalent (AS04 adjuvated) HPV vaccine induces superior immune responses compared with quadrivalent HPV vaccine without affecting graft function in kidney transplant recipients. ;Secondary Objective: Secundary objectives 1.To compare immunogenicity of HPV vaccination among kidney transplant candidates and recipients. 2.To investigate the impact of in vivo toll-like receptor (TLR) 4 priming (by the AS04 adjuvant in bivalent HPV vaccine) on innate and adaptive immune signaling and activation,and to identify immunological predictors of vaccine response 3.To determine the induction of cellular immunity against HPV16 and 18 L1 antigen following HPV immunization ;Primary end point(s): Geometric mean titres (GMT) of neutralizing HPV-16 and -18 serum antibodies measured by pseudovirion based neutralization assay at day 210 after first vaccination with either bivalent HPV vaccine (Cervarix®, GSK) or quadrivalent HPV vaccine (Gardasil®, Merck) ;Timepoint(s) of evaluation of this end point: Day 210 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Geometric mean titres (GMT) of neutralizing HPV-16 and -18 serum antibodies measured by pseudovirion based neutralization assay Geometric mean titres (GMT) of neutralizing HPV-31, 45, 52, and 58 serum antibodies measured by pseudovirion based neutralization assay -Geometric mean titres (GMT) of antibodies against 40 HPV types (Luminex) -Presence of anal/cervical/penile HPV DNA at inclusion -Presence of cervical dysplasia at inclusion -HLA antibodies (transplant recipients) -Cytokine concentrations related to TH1/TH2/TH17 cellular responses (e.g., IL-2, IL-4, IL-5, IL-6, IL-7, IL-12, IL-17A, IP-10, TNF-a, INF-a, INF- ?) in stimulated PBMCs (stimulated with TLR-4 agonist or bacterial pathogens and by HPV antigen) B cell profile (CD3, CD19, CD20, CD27, CD38, IgM, IgD), T cell profile (CD3, CD4, CD27, CD38, CD45RA, CCR7), regulatory T cell profile (Live/Dead, CD3, CD4, CD25, CD127, FoxP3), and TH17 cell profile (Live/Dead, CD3, CD4, CD8, IL17A, IL21) by Flow Cytometry (FACSCantoII, BD Biosciences, San Jose, CA, USA). -Impact of HPV immunization on cellular immunity against HPV:ts: Single, double, and triple cytokine-producing HPV16 and HPV18 L1 antigen-specific CD4 and CD8 T cells determined by intracellular cytokine staining (INF-?, TNF-a, and IL2) and extracellular staining (CD3, CD4, and CD8) by flow cytometry. Counts and fractions of antigen-specific CD4 and CD8 T cells are compared with and without stratification for vaccine allocation. PBMC supernatant cytokine concentrations (e.g., IL-2, IL-4, IL-5, IL-6, IL-7, IL-12, IP-10, TNF-a, INF-a, INF- ?) measured by as outlined above. ;Timepoint(s) of evaluation of this end point: At day 0, 45,180 ,210 and 360 unless otherwise stated below -Geometric mean titres (GMT) of antibodies against 40 HPV types (Luminex): Day 0,210 and 360 HPV DNA : Day 0 Cervical Dysplasia: Day 0 HLA antibodies: Day 0,210 and 360 B and T cell profiles: Day 0 | — |
Countries
Denmark
Contacts
Public ContactLars Dalgaard
Department of Infectious Diseases
Outcome results
None listed