Immunogenicity of HPV Vaccine in Immunosuppressed Children

Immunogenicity and Duration of Immunity in Immunosuppressed Children Vaccinated With Quadrivalent HPV Vaccine

Genital HPV is the necessary cause for cervical cancer, as well as a major contributing cause of several other cancers and conditions. There are now effective vaccines against the main oncogenic HPV types, HPV16 and 18.

Most research and discussion has focused on targeting the vaccine to young women and older adolescents. Based on this, a national free HPV vaccination program for adolescent girls commenced in 2007, in Australia. However, at the time of commencement, there had been no research on the use of this vaccine in immunosuppressed. Therefore, information on the immunogenicity, safety and duration of efficacy of HPV vaccine when administered to immunosuppressed children is needed. This trial looked at a 3 dose schedule of quadrivalent HPV vaccine in a range of immunosuppressed children, with the endpoint being immunogenicity, followed for 5 years for duration of immunity.

Study Overview

• Status: Completed
• Conditions: Kidney Transplant Infection; Juvenile Idiopathic Arthritis; Inflammatory Bowel Disease; Autoimmune Disease; Evidence of Liver Transplantation; Bone Marrow Transplant Infection
• Intervention / Treatment: Biological: Quadrivalent HPV vaccine

Detailed Description

To determine the immunogenicity, safety and persistence of immunity following human papillomavirus (HPV) vaccination in three groups of immunosuppressed children: recipients of allogenic bone marrow transplant, recipients of renal and liver transplants, and patients with juvenile chronic arthritis, inflammatory bowel disease and other autoimmune conditions who are on longterm immunosuppressive therapy.

Significance: Immunosuppressed populations are diverse in terms of degree, type and duration of immunosuppression. The study compares several groups in order to address the heterogeneity of immunosuppression and how this affects vaccine response. BMT patients have extreme, severe immunosuppression in the short term, but recover immune function with time. In contrast, solid organ transplant recipients have ongoing, chronic immunosuppression. Although successful cessation of immunosuppressives in liver transplant patients has been reported, most patients require ongoing treatment. The inflammatory bowel disease group of patients represents a non-transplant group who require ongoing, often low level immunosuppression, often with corticosteroids. Our study will compare these three groups, followed up for five years for duration of immunity. Time of vaccines, time of serological measures of immune response are as follows.

Serum collections:

0 - Baseline (before HPV vaccine dose 1); 2 months - At the time of receipt of HPV vaccine dose 2 (to measure response to dose 1); 6 months - At the time of receipt of HPV vaccine dose 3 (to measure response to dose 2); 7 months - 1 month after HPV vaccine dose 3; 12 months - after HPV vaccine dose 1; 2 years after HPV vaccine dose 1; 3 years after HPV vaccine dose 1; 4 years after HPV vaccine dose 1; 5 years after HPV vaccine dose 1.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2052
      • School of Public Health and Community Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- Immunosuppressed patients with following diseases; Bone marrow transplant recipients, liver transplant patients, renal transplant, Children with inflammatory bowel disease, juvenile Idiopathic arthritis and autoimmune conditions.

Exclusion Criteria:

• A platelet count of <50
• Immunoglobulin therapy within 3 months.
• Yeast allergy
• Any other known allergies to one of the vaccine component

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HPV vaccine; Quadrivalent HPV vaccine	Biological: Quadrivalent HPV vaccine; Three 0.5 mL doses will be given at time 0, 2 months after the 1st dose and then 6 months after the initial dose. For kidney transplant recipients the first dose will be at least 6 months post-transplant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity	Indicator: Geometric mean four fold rises (with 95% confidence intervals) of the vaccine serotype specific IgG antibody in all participants.; Proportion of subjects achieving a 4 fold rise in antibody titre for each serotype. Serum antibody levels will be measured using a Luminex immunoassay. Analysis: For each individual, the change in log-22FA levels for each serotype pre-post vaccination will be calculated. The average change will then be compared over time for each group and also between healthy and immunosuppressed groups using t-tests. Geometric mean titres of antibody for each serotype will be measured and compared at each follow up interval.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of immunity	Interpretation of Results: Persistance of immunity will be measured over 5 years, as well as the comparison of immunogenicity by immune status.	5 years

Collaborators and Investigators

• Sponsor: The University of New South Wales
• Collaborators: Sydney Children's Hospitals Network; Women's and Children's Hospital, Australia
• Investigators: Principal Investigator: Raina MacIntyre, The University of New South Wales

Publications and helpful links

General Publications

• MacIntyre CR, Shaw P, Mackie FE, Boros C, Marshall H, Barnes M, Seale H, Kennedy SE, Moa A, Hayen A, Chughtai AA, O'Loughlin EV, Stormon M. Immunogenicity and persistence of immunity of a quadrivalent Human Papillomavirus (HPV) vaccine in immunocompromised children. Vaccine. 2016 Aug 5;34(36):4343-50. doi: 10.1016/j.vaccine.2016.06.049. Epub 2016 Jul 9.
• MacIntyre CR, Shaw PJ, Mackie FE, Boros C, Marshall H, Seale H, Kennedy SE, Moa A, Chughtai AA, Trent M, O'Loughlin EV, Stormon M. Long term follow up of persistence of immunity following quadrivalent Human Papillomavirus (HPV) vaccine in immunocompromised children. Vaccine. 2019 Sep 3;37(37):5630-5636. doi: 10.1016/j.vaccine.2019.07.072. Epub 2019 Aug 8.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2007
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: October 3, 2014
• First Submitted That Met QC Criteria: October 8, 2014
• First Posted (Estimated): October 13, 2014

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: HPV vaccine, children, immunocompromised
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Immune System Diseases; Disease Attributes; Gastrointestinal Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Gastroenteritis; Arthritis; Intestinal Diseases; Infections; Communicable Diseases; Inflammatory Bowel Diseases; Autoimmune Diseases; Arthritis, Juvenile
• Other Study ID Numbers: 2007/028

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We would like to share publication(s) that may arise from the study when applicable.