The main objective of this trial will be to get a better insight in the influence of age and age-related changes by internal and external factors on vaccine-induced immune responses and gain knowledge on the trajectory of immune decline in older…
ID
Source
Brief title
Condition
- Other condition
- Viral infectious disorders
Synonym
Health condition
immuunsysteem
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoints are to compare vaccine-induced specific serum antibody
levels for both the influenza quadrivalent influenza vaccine (QIV) and the
pneumococcal PCV13 vaccine (geometric mean titters (GMTs) for influenza and
geometric mean concentrations (GMCs) for pneumococcal vaccine* in older adults
with those in middle-aged adults and adults one month post vaccination.
Secondary outcome
The secondary parameters/endpoints are:
1) to compare induction and persistence of vaccine-induced serum antibody and T
cell responses by measurement of vaccine-specific antibody titers and specific
T-cell immunity pre- and post-vaccination between older adults, middle-aged
adults and adults.
2) to determine the impact of (changes in) clinical baseline and
(immunological) biomarker status as candidate predictive markers for vaccine
responsiveness. Data collected in questionnaires (a.o. general health and
quality of life, medical history and life style) and by measurements of local
and systemic immune status and systemic cellular composition will be correlated
with vaccine responses and compared across older adults, middle-aged adults and
adults.
Exploratory endpoints consist of in-depth analysis of the quality of the
vaccine-induced innate, humoral (local and systemic) and cellular immune
responses, and compare the impact of the biological and genetic baseline status
on the vaccine responses between older adults, middle-aged adults and adults.
Background summary
Due to the increase in the percentage of adults of 65 years and older, a
population that is more vulnerable to infections due to a decline in immune
responses with ageing (immunosenescence), the number of people with severe
infectious disease-related health problems is increasing. Vaccines are one of
the most effective means to protect against different infections. However, the
responses to vaccines in elderly may vary considerably. All participants will
receive a seasonal influenza vaccine, and a pneumococcal vaccine and optional a
COVID-19 vaccine to study different vaccine concepts in the same individuals.
The influenza vaccine will induce a booster response since only subjects who
have had an influenza vaccination in the previous year will be included,
whereas the pneumococcal vaccine will be the first dose inducing a primary
response to the vaccine serotypes. The COVID-19 vaccine is a combination of
prime-boost vaccination with an mRNA vaccine concept. This approach allows
comparison of primary and booster(s) vaccine response from different vaccine
concepts in the different age groups. Knowledge on which parameters of the
immune system or external factors contribute to decreased immune responsiveness
to vaccines can provide leads to improve vaccine responsiveness in general. In
addition, this information can be used to predict effective or non-effective
immune responses in specific subsets of individuals. Eventually this
information may help to design optimal future vaccination strategies.
Study objective
The main objective of this trial will be to get a better insight in the
influence of age and age-related changes by internal and external factors on
vaccine-induced immune responses and gain knowledge on the trajectory of immune
decline in older adults, pre-elderly (middle-aged) adults in comparison to
adults with the ultimate goal to formulate evidence-based strategies to improve
immunity to vaccines in the ageing population.
Study design
Longitudinal intervention study
Intervention
All subjects will receive the seasonal quadrivalent inactivated influenza
vaccine (QIV) (2019-2020) (autumn 2019) and the 13-valent pneumococcal
conjugate vaccine (PCV13) (spring 2020- spring 2021) and optionally an mRNA
COVID-19 (booster(s)) vaccine.
Study burden and risks
The burden associated with participation involves collection of blood samples
by venipuncture (9 times; 48 to 107 ml per visit with a mean total volume of
634 ml over an 24 month period), blood collection by fingerstick (2 time 300
ul), nasopharyngeal and oropharyngeal swabs (3 times), saliva samples (5 times)
and feces (2 times). In case of participation to the SARS-CoV-2 sub study,
additional visits involves collection of blood by venipuncture (4 times, 7-43
ml per visit, with a mean total volume of 64ml over 12 month period), blood
collection by fingerstick (1 time, 300 µl) and nasopharyngeal and oropharyngeal
swabs (4 times). Participants of the SARS-CoV-2 booster dose response study,
will have a vaccination/blood collection visit and 3 follow-up finger prick
collections over a 12 month period. A subset of the participants will be asked
to three times donate a larger blood volume collected by venipuncture during
study visits (44 ml per visit) and 1 additional fingerstick blood sample (1
time 300 ul),
3 additional nose (or saliva) fluids samples. All booster dose participants
will be asked to complete a total of
4 additional questionnaires. For these participants the 12 months post second
COVID vaccine dose follow-up visit (visit Te) will not be performed.
All extra SARS-CoV-2 booster participants will have a vaccination/ blood
collection and 3 follow-up finger prick collections (4x 300uL) over a 12 month
period. Depending on the timing of the extra booster, one or multiple
timepoints of the previous booster study will be skipped.
In the autumn of 2022 all participants older than 60 years of age were invited
for the follow up of the autumn 2022 COVID-19 booster vaccination. The
follow-up was comparable to the follow-up of the previous boosters, as
previously described, which included additional blood collection timepoints 1
month, 6 months and12 months post vaccination (3x, 300uL for for the finger
pricks). For the subgroup the timepoint 1 months and 6 months post vaccinations
will be a venipuncture (44mL per home visit). The pre-vaccination sample will
replace the last timepoint of the previous booster. Analysis of immunological
response to additional autumn 2023 COVID-19 booster vaccination will require
additional blood collection timepoints 1 month and 12 months post vaccination
(3x, 30uL for finger pricks). For the subgroup, the pre and 1 month post
vaccination will be venipuncture (44mL per home visit) and mucosal lining fluid
will be collected. The timepoint 12 months post vaccination will include a
fingerprick and the collection of mucosal lining fluid for all the
participants. The pre-vaccination sample will coincide with 12 month post
autumn 2022 booster vaccination timepoint.
All participants will receive a pneumococcal vaccination that they otherwise
would not have had. In addition, the subject will be asked to fill in
questionnaires, perform a grip strength test (3 times) and have the blood
pressure measured (3 times). The samples and results of the measurements (such
as blood pressure and grip test) will be collected during a total of 11 visits.
For the oldest age group, visits will be home visits, whereas for the other two
age groups, visits will be at a study location close to their office/work.
The potential risks are considered minimal. The pneumococcal vaccine has been
registered in Europe and the US and has been used for several years in children
and adults. Adverse events related to pneumococcal vaccination are comparable
with events associated with other vaccines such as local injection site
reactions, general fatigue, headache, diarrhea and vomiting. The benefit for
the individual subjects who participate in this trial is protection against
pneumococcal disease (e.g. pneumonia, sepsis and meningitis) by vaccination
with a pneumococcal conjugate vaccine (PCV13). The results of the study may
contribute to a better control of respiratory diseases in older age groups on a
population level in the future. All subjects are eligible for influenza
vaccination and therefore influenza vaccination is not considered a benefit for
this study population.
Antonie van Leeuwenhoeklaan 9
Bilthoven 3721 MA
NL
Antonie van Leeuwenhoeklaan 9
Bilthoven 3721 MA
NL
Listed location countries
Age
Inclusion criteria
•Be 25 years or older at the time of inclusion.
•Have received a seasonal influenza vaccination in previous season (2018-2019).
•Be capacitated.
•Have signed Informed Consent
Exclusion criteria
•Having had a previous pneumococcal vaccination (PCV or the 23-valent
pneumococcal polysaccharide vaccine (PPV23)).
•Known or suspected allergy to any of the vaccine components or having
experienced a previous severe adverse reaction to any vaccine.
•Receipt of any high-dose (>= 20 mg of prednisone daily or equivalent) daily
corticosteroids (local incl. inhaled steroids are acceptable) within 2 weeks of
study entry
•Repeated use of any high dose of corticosteroids (a dose of > 30 mg of
prednisone or equivalent per day for multiple days) in the recent past.
•Receipt of an organ- or bone marrow transplant
•Have a (functional) asplenie.
•Receipt of chemotherapy in the last 3 years.
•Receipt of blood products or immunoglobulin, within three months of study
entry.
•Known or suspected coagulation disorder that in the opinion of the
investigator would contraindicate against receiving an intramuscular injection
or undergo frequent blood sampling.
•Known anemia, measured as Hb < ( 8,5 mmol/l for men and 7,5 mmol/l for woman;
NHG standard Anemia)
•Known to be positive for human immunodeficiency virus (HIV), and/or hepatitis
C virus (HCV) and/or hepatitis B virus (HBV).
•Known or suspected immunodeficiency or use of immunosuppressive therapy that
according to the investigator, in consultation with a medical expert,
contraindicates a Prevnar-13 vaccination.
Exclusion criteria COVID-19 vaccination study
•Treatment with COVID-19 monoclonal antibodies less that 3 months before
COVID-19 vaccination.
•Known pregnancy at the moment of COVID-19 vaccination.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-000836-24-NL |
| CCMO | NL69701.041.19 |