Investigate the effects of aP booster vaccination in children, young adults and elderly on the (long-term) immune response to B. pertussis in three European countries with a different epidemiological background and primary vaccination schedule for…
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Source
Brief title
Condition
- Bacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
PT specific IgG antibodies at day 28 (T4).
Secondary outcome
Secondary study parameters/outcome of the study (if applicable):
*PT specific IgG antibodies and their avidity at T0, T4 and T5.
Specific IgG-levels to other pertussis vaccine antigens, as well as to
non-pertussis antigens will be determined at T0, T4 and T5, using a PERISCOPE
serological multiplex immunoassay.
* Functional pertussis-specific antibody levels will be determined in serum
samples at T0, T4 and T5, using PERISCOPE core assays as described in section
8.3.4. Differences in levels of functional antibodies will be measured before
and after vaccination. Functional antibody assays include bacterial adherence
inhibition (BAI), PT neutralisation (PTNA), serum bactericidal activity (SBA),
and bacterial opsonophagocytosis assay (OPA). Other serological parameters such
as avidity, subclass distribution (IgA, IgM) are optional in serum samples.
* Antigen-specific memory B cell responses at time points T0, T2, T4 and T5
will be measured to determine the effects of aP booster vaccination in
children, young adults and elderly, using PERISCOPE B cell core assay.
* Characterisation of the effect of an aP booster on the specific T cell immune
response, both early after the boost and later on, in different age groups,
vaccinated initially either with a whole cell or an acellular vaccine.
* Collection and biobanking of biological samples to be used for testing in
novel exploratory immunoassays and for possible bridging to other pertussis
vaccine studies.
Exploratory study parameters/outcome of the study (if applicable):
* Differences in T cell programming will be measured on fresh blood samples
or frozen PBMC samples in an exploratory PERISCOPE T cell assay. This assay
includes but is not limited to multi-colour flow cytometry and/or mass
cytometry (CyTOF), combined with supernatant cytokine analysis.
* To assess differences in epigenetic imprinting of immune cells by primary
vaccination on dTap-IPV booster vaccination, material for epigenetic markers
will be isolated before and after vaccination. If differences in (functional)
immunological memory are observed, epigenetic markers related to immune
function will be analysed.
* Gene expression differences in response to dTap-IPV booster vaccination will
be measured in immune cells, from before and after vaccination.
* Intra-individual changes in cell subsets in response to vaccination will be
measured on fresh blood samples by flow cytometry (EuroFlow) and/or mass
cytometry (CyTOF).
* Changes in the B cell receptor repertoire will be examined, as this will
provide information on the impact of vaccination in different priming
backgrounds and ages.
* Cytokine production will be evaluated after ex vivo restimulation of
PBMCs/whole blood, and potentially also directly in serum, taken before and
after vaccination.
* The soluble factors in the eluate from nasosorption (including
cytokines/chemokines) will be analysed by Luminex MIA, BAI and SBA.
Background summary
Pertussis, or whooping cough, is caused by the bacterium Bordetella pertussis
(B. pertussis) and is an acute and serious respiratory infection, in particular
for young and unvaccinated children. However, despite high vaccination coverage
(95%), pertussis is re-emerging in the Netherlands since 1996. This phenomenon
is also observed in most other western countries. The most recent epidemic in
2012 in the United Kingdom (UK) and the Netherlands highlighted the
vulnerability of infants for a pertussis infection, causing 15 deaths all
together. The pertussis infection rate in adolescents and adults has increased
as well in the past years. This elevated incidence in adults is a risk factor
for young babies, since infants are most often infected with B. pertussis
through their mother.
The main purpose of this study is to investigate the dynamics and longitudinal
effects of an acellular pertussis (aP) booster vaccination in children, young
adults and elderly, on long-term humoral and cellular memory immunity against
B. pertussis. The study will be performed in three European countries (UK,
Finland and the Netherlands) with a different epidemiological background for
pertussis incidence. In addition, different age groups had different primary
schedules with whole cell pertussis (wP) or aP vaccines in their first year of
life. Long-term memory responses will be analysed following aP booster
vaccination to provide a detailed understanding of immunity to B. pertussis and
to assess novel biomarkers as potential surrogates of long-lived protective
immunity. This will include a detailed assessment of antigen-specific B and T
cell responses and serology assays for pertussis antigens. In addition, the
effect of booster vaccination on dynamic changes in immune cell subsets and
gene transcription will be investigated.
Study objective
Investigate the effects of aP booster vaccination in children, young adults and
elderly on the (long-term) immune response to B. pertussis in three European
countries with a different epidemiological background and primary vaccination
schedule for pertussis.
Study design
longitudinal intervention study
Intervention
Participants will receive one injection of reduced diphtheria toxoid, tetanus
toxoid and reduced acellular pertussis vaccine (dTap)-IPV, (Boostrix® IPV,
GlaxoSmithKline (GSK)) combination vaccine intramuscularly in the upper arm.
Mucosal samples will be taken before (T0), at 28 days (T4) and 1 year (T5)
after vaccination. Venous blood samples will be drawn at T0 and at 1 (T1), 7
(T2), 14 (T3) days post-intervention, T4 and T5. Adults (cohorts C and D) will
donate blood samples at T0, T2, T3, T4 and T5. Children will donate only at
selected time points. All children in cohorts A and B will donate blood samples
at T0, T4 and T5. Additionally, the children will be further divided in
subcohorts for additional blood draws at one of the following time points:
cohorts A at T2 or T3, cohort B at T1, T2 or T3. Summarising, children will be
asked to donate blood 4 times, and young adults and elderly will be asked to
donate blood 5 times in total over the entire study duration of 12 months.
Mucosal samples will be taken at T0, T4 en T5.
Study burden and risks
Participants will benefit from participating in this study by receiving an
additional Boostrix® IPV vaccination. From the worldwide public health
perspective, participation in this study will contribute to insight in
pertussis immunity. Although vaccination and especially venepunctures may be
unpleasant, they are considered low risk invasive procedures. These risks will
be mitigated by the performance of all procedures by experienced personnel. The
sampling frequency is intensive for the young adults and elderly. To minimise
sampling frequency for children, cohorts A and B will be divided into one of
the subcohorts (i.e. the three *fixed* time points plus one additional time
point). This will also minimise the total blood volume drawn from children in
the first two weeks post-intervention.
Boostrix® IPV is a registered vaccine. Adverse reactions (ARs) to the vaccine
may occur but they are expected to be mainly local and transient. Severe
allergic reactions to one of the vaccine components are unlikely to occur.
Boostrix® IPV booster vaccination in children and adults is a common procedure
in a large number of countries already.
Antonie van Leeuwenhoeklaan 9
Bilthoven 3721 MA
NL
Antonie van Leeuwenhoeklaan 9
Bilthoven 3721 MA
NL
Listed location countries
Age
Inclusion criteria
* normal general health;
* within the right age group for the cohort;
* received all regular vaccines for their age group according to the Dutch National immunisation programme (NIP), UK NIP or Finnish NIP; a copy of the vaccination booklet will be included in the participant*s documents. If booklet is not available for cohorts A, B and C, vaccination status will be checked with regulatory agencies / General practitioner. For cohort D this booklet might not be available due to their age;
* provision of written informed consent (see section 11.2 for details);
* willing to adhere to the protocol and be available during the study period.
Exclusion criteria
* present evidence of serious disease(s) within the last 3 months before inclusion requiring immunosuppressive or immune modulating medical treatment, such as systemic corticosteroids, that might interfere with the results of the study;
* chronic infection;
* known or suspected immune deficiency;
* history of any neurologic disorder, including epilepsy;
* previous administration of serum products (including immunoglobulins) within 6 months before vaccination and blood sampling;
* known or suspected allergy to any of the vaccine components (by medical history);
* occurrence of serious adverse events (SAEs) after primary DTwP-IPV (Diphtheria, Tetanus, whole-cell Pertussis, Polio) vaccination, DTaP-IPV (Diphtheria, Tetanus, acellular Pertussis, Polio) vaccination or any other vaccination (by medical history);
* vaccination with any other pertussis vaccine than those described in the inclusion criteria (i.e. only according to NIP);
* vaccination with any other Diphtheria, Tetanus and polio (DT-IPV) vaccine in the last 5 years, DT-IPV vaccination according to NIP in cohort B is no exclusion;
* children between 8 and 10 years of age eligible for cohort A in the Netherlands who have already received the DT-IPV booster vaccination according to the Dutch NIP around 9 years of age;
* mixed whole-cell pertussis (wP) and acellular pertussis (aP) priming within a participant, cohort B;
* Pregnancy
Design
Recruitment
Medical products/devices used
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-003678-42-NL |
| CCMO | NL60807.100.17 |