Condition category
Infections and Infestations
Date applied
29/04/2008
Date assigned
07/11/2008
Last edited
07/11/2008
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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 measures

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

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

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

http://www.rivm.nl/en/

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes