Observational Follow up of Prior HPV Vaccinees (HPVfollowup)
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|ClinicalTrials.gov Identifier: NCT02811068|
Recruitment Status : Completed
First Posted : June 23, 2016
Last Update Posted : April 10, 2018
|Condition or disease||Intervention/treatment|
|Human Papillomavirus Virus||Other: venepuncture|
Since September 2008, Human Papillomavirus (HPV) vaccines have been offered as part of the UK national immunisation schedule to adolescent females, first as three doses of a bivalent vaccine (Cervarix) covering the two most common strains (HPV16 and 18). Subsequently a quadrivalent vaccine was given in 2012 (Gardasil) incorporating a further two HPV types (HPV6 and 11). Between 2009 and 2011, the National Vaccine Evaluation Consortium (NVEC) conducted a randomised, observer-blinded parallel group study to evaluate the immunogenicity of the two HPV vaccines in terms of humoral immune responses against vaccine and non-vaccine incorporated HPV genotypes. The investigators plan to approach the participants of the original study as part of a follow up study to assess the duration of the humoral immune response elicited to the HPV vaccines; specifically, comparing the breadth and magnitude of antibody responses against vaccine and non-vaccine incorporated genotypes 5.7-6.8years on from their first dose of vaccine.
Long-term follow up studies have been conducted up to 9.4 years post vaccination for example in a multicentre double-blinded trial evaluating the long term efficacy of the Cervarix vaccine, which demonstrated 95-100% sustained efficacy against incident infection and CIN1+/2+ lesions whilst antibody titres were above those seen with natural infection adding confidence to the long term efficacy of this vaccine . The quadrivalent vaccine has been evaluated in long term follow up studies for example in a continuation of the Future II study at 9 years post first dose, whereby ≥94% of samples were seropositive for types 6,11 and 16 and 60% for HPV18 according to a cut-off negative serostatus value decided on by a selection of naïve and seropositive sera. There was also minimal difference in titres compared to months 18 and 48, representing a stable plateau of seroprotective titres. There are only two studies that have examined the duration of antibody responses against non-vaccine genotypes beyond 12 months: one comparing antibody titers elicited by both HPV vaccines against HPV31 and HPV45 in 18-26 year old women 24 months post first dose and one describing HPV31 seropositivity in 18-25 year old women at 48 months. This study will therefore provide unique data for the age group that HPV vaccination is offered to in the UK, in terms of vaccine incorporated genotypes as there are a limited number of follow up studies evaluating the 12-15 year old age group, as well as assessing the duration of antibody responses against non-vaccine types which has been far less extensively studied in all age groups.
A minimum antibody titre that correlates with HPV vaccine efficacy has not been defined; that is, a so-called correlate of protection. For HPV16 and HPV18 this is, in part, due to the high levels of HPV antibody generated following vaccination and the lack of breakthrough infections in vaccine trials. For non-vaccine genotypes where efficacy is only partial, further information on the breadth, magnitude and duration of such antibody specificities is required before a correlate (or surrogate) of protection can be established .
There is evidence to suggest robust immunological memory from studies looking at booster doses of HPV vaccine, which could be introduced into the UK programme to ensure protection throughout a women's sexual lifetime. For instance, in a follow up study assessing the immunological response to a booster dose of Cervarix seven years following immunisation with a three dose schedule, a strong memory B cell response persists after vaccination, giving rise to significantly higher GMTs than observed following the first dose of the bivalent vaccine. A significant fold-increase in GMTs was also observed with a booster dose following two doses of the quadrivalent vaccine, though GMTs were higher following a bivalent booster.
This follow up study will begin to address the question of long term durability of HPV vaccine antibody responses afforded by the HPV vaccines in the target age group in the UK population and therefore whether changes need to be made to the current national schedule.
|Study Type :||Observational|
|Estimated Enrollment :||198 participants|
|Official Title:||An Observational Follow up Study of a Randomised Parallel Group Phase IV Study to Evaluate the Duration of the Immune Response to Vaccine and Non-vaccine HPV Types in UK Adolescent Females Who Received Either Cervarix or Gardasil Human Papillomavirus (HPV) Vaccines|
|Actual Study Start Date :||December 2016|
|Actual Primary Completion Date :||August 2017|
|Actual Study Completion Date :||December 2017|
Collection of single blood sample to assess antibody persistence over time
- HPV immunogenicity [ Time Frame: single timepoint per participant, over the duration of the study which is anticipated to be 12 months ]antibody titres elicited to HPV vaccine and non-vaccine types following vaccination with either Cervarix(R) or Gardasil(R) at 5-7 years post first immunisation and comparison between vaccines and over time
Biospecimen Retention: Samples Without DNA
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02811068
|Gloucestershire primary care|
|Gloucestershire, United Kingdom|
|Hertfordshire primary care|
|Hertfordshire, United Kingdom|
|Principal Investigator:||Paul Turner, MD PhD||Public Health England|