Contact information
Type
Scientific
Primary contact
Mrs Lotte Hendrikx
ORCID ID
Contact details
Antoni van Leeuwenhoeklaan 9
Postbak 22
Bilthoven
3720 BA
Netherlands
+31 (0)30 274 3944
Lotte.Hendrikx@rivm.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
LTR137
Study information
Scientific title
Long-term cellular memory immunity against Bordetella pertussis and other components of the DTP-IPV-Hib vaccine in Dutch children: comparison of a whole cell vaccine (WCV) with an acellular vaccine (ACV) - observational study
Acronym
Study hypothesis
Whooping cough is a respiratory disease, caused by Bordetella pertussis. Whooping cough is a serious disease in the young, vulnerable infant. Older children and adults are the main source of infection. Since 1996 the incidence of whooping cough is increasing in the Netherlands. Since the acellular vaccine (ACV) against whooping cough (pertussis) was introduced in the Netherlands in 2005 and qualitative differences in infant immunity to ACV and whole cell vaccine (WCV) have been described, cellular immunity and memory against pertussis need to be addressed. Both vaccines are given at an age when the immune system is not yet fully developed and the (long term) effects of this major change in the vaccination programme are largely unknown. This study aims to investigate the effects of the switch from WCV to ACV on the long-term protective immunity against pertussis and on the development of the immune system. Furthermore, the influence on the TH1/TH2 balance differs between the cellular and acellular pertussis vaccinations and will be further investigated after booster vaccination at 4 years with ACV.
Ethics approval
Medical Ethics Committee, Almere (Medische Ethische Toestingscommissie [METC] te Almere). Date of approval: 03/04/2006 (ref: R06-025)
Study design
Observational cohort multicentre study
Primary study design
Observational
Secondary study design
Cohort study
Trial setting
Other
Trial type
Prevention
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Whooping cough/ Bordetella pertussis infection
Intervention
This is an observational, cohort study. Recruitment will be carried out in two stages.
Populations of children at different ages who already had received four vaccinations at 2, 3, 4 and 11 months with the whole cell vaccine DTPwcv-IPV-(Hib) were recruited in 2006 as follows:
3 years old: 2 year after the forth priming vaccination at 11 months
4 years old: before the booster vaccination with ACV
4 years old: 10 (+/-1 day) days after the booster vaccination with ACV
(Triaxis®)
4 years old: 28 (+/-3 days) days after the booster vaccination with ACV
(Triaxis®)
4 years old: 28 (+/-3 days) days after the booster vaccination with ACV
(Infanrix®-IPV)
6 years old: 2 years after the booster vaccination with ACV
9 years old: 5 years after the booster vaccination with ACV
One blood sample was taken, and questionnaires (including questions concerning clinical manifestations of allergic reactions) were carried out.
For comparison, the same age groups of children (but different children from the previous recruitment) who already had received four vaccinations at 2, 3, 4 and 11 months with the acellular vaccine DTPacv-IPV-(Hib) (Infanrix®-IPV) will be recruited from 2008 till 2015.
B- and T-cells will be isolated and enzyme-linked immunosorbent spots (ELIspots) will be carried out. In a multiple immuno beads assay, the antibody titres will be measured.
Intervention type
Biological/Vaccine
Phase
Not Specified
Drug names
Primary outcome measure
B cell and T cell immune responses:
Peripheral blood mononuclear cells (PBMC's) will be isolated from the blood samples. PBMC's will be divided in purified B cell populations and T cell populations. B cells will be cultured and memory B cells will be polyclonal stimulated. After 5 days stimulation, B cell memory responses will be measured against the various proteins of B pertussis (filamentous hemagglutinin adhesin [FHA], pertactin [PRN], pertussis toxin [PT], fimbriae [Fim], lipopolysaccharide [LPS]) by ELIspot assays and enzyme-linked immunosorbent assay (ELISA)/Luminex® of the culture supernatants.
T cells will be stimulated with the various proteins of B. pertussis and at 24 hours and 5 days of culture, cells and supernatants will be harvested. Memory T cell responses will be measured by IFN-y and/or IL2 ELIspot assays. TH1/TH2 ratios will be measured by analysing cytokines in the culture supernatants by Luminex® bead protein assay or ELISA.
All data collection will be completed by the end of 2010.
Secondary outcome measures
Blood samples will be separated in PBMC's and plasma samples. The plasma samples will be used to measure antibody responses against the various proteins of B. pertussis as well as against the other proteins of the DKT-IPV-HIB vaccine.
Plasma parameter assays:
1. Pertussis (PT, PRN, FHA, FIM2 and FIM3): IgG antibody titer is measured in an ELISA/Luminex® with two-fold serial dilution series in duplicate using FDA reference serum as standard (EU/ml)
2. Diphtheria, tetanus: IgG antibody titer is measured in a ToBI-ELSA/Luminex® with twofold serial dilution series in duplicate using the national reference serum (IU/ml) as standard which is calibrated on the World Health Organization (WHO) standard
3. Haemophilus influenzae type b (Hib): IgG antibody titer is measured in an ELISA/Luminex® with two-fold serial dilution series in duplicate using CBER-FDA reference serum as standard (µg/ml)
4. Polio: total Ig is measured in a neutralisation assay on Vero cells with two-fold serial dilution series in duplicate using the WHO reference serum as standard
5. To monitor the effect of WCV or ACV on TH2 mediated disease manifestations, total IgE levels and some components of the DTP-IPV-Hib vaccine (PT and tetanus) will be measured in the plasma
6. Mucosal IgA antibodies will be measured in the plasmas
All data collection will be completed by the end of 2010.
Overall trial start date
01/09/2006
Overall trial end date
18/12/2007
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Both male and female children, aged 3 to 9 years old
2. Infants in good general health (eligible) who have been vaccinated according to the Dutch national vaccination programme
3. Provision of written informed consent by both parents and legal representatives
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
420
Total final enrolment
338
Participant exclusion criteria
1. Present evidence of serious disease(s) demanding immunosuppressive medical treatment, such as corticosteroids, that might interfere with the results of the study within 3 months
2. Any known primary or secondary immunodeficiency
3. Vaccination with any other vaccine than those used in the National Immunisation Programme (Rijks Vaccinatie Programma [RVP]) within a month before the blood sampling
Recruitment start date
01/09/2006
Recruitment end date
18/12/2007
Locations
Countries of recruitment
Netherlands
Trial participating centre
Antoni van Leeuwenhoeklaan 9
Bilthoven
3720 BA
Netherlands
Sponsor information
Organisation
National Institute for Public Health and the Environment (RIVM) (The Netherlands)
Sponsor details
Antoni van Leeuwenhoeklaan 9
Bilthoven
3720 BA
Netherlands
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
National Institute for Public Health and the Environment (RIVM) (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2013 results in: https://www.ncbi.nlm.nih.gov/pubmed/23825195 (added 04/07/2019)