Human Papillomavirus Virus Clinical Trial
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
HPV vaccines have been included in the national immunisation schedule since 2008, firstly as the Cervarix vaccine which protects against two HPV types and in 2012 as the Gardasil vaccine which offers protection against a further two HPV types. This study will assess whether booster doses are indicated to protect females throughout their lifetime or if the vaccinations offered in early adolescence provide this by following up a cohort from a previous study where female adolescents were vaccinated 5-7 years ago.
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.
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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT03000998 -
Web App Technology for Boys and Parents: Improving HPV Vaccine Uptake
|
N/A |