Primary objective is to study the antibody immune response to routine vaccinations in very preterm infants (GA
ID
Source
Brief title
Condition
- Other condition
- Immunodeficiency syndromes
- Infections - pathogen unspecified
Synonym
Health condition
respons op vaccinaties
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To measure blood IgG antibody concentrations against the antigen components of
the hexavalent DTaP5-HB-IPV-Hib vaccine for the six preventable diseases
(Diphtheria, Tetanus, Pertussis, Polio, Hepatitis-B, Haemophilus influenza type
B) in preterm-born infants 4- 6 weeks after primary series of routine
vaccinations in order to assess the proportion of children with IgG
concentrations above international-defined thresholds for protection. This
proportion will be compared with proportions in healthy term infants as known
from literature. .
Secondary outcome
1. To assess the number and repertoire of blood antigen-specific memory B cells
in term-born infants following routine vaccinations after primary series (age 6
months) and booster vaccination (age 12 months)
2. To assess number and repertoire of blood antigen-specific memory B cells in
preterm-born infants following routine vaccinations after primary series (age 6
months) and booster vaccination (age 12 months) compared to term born infants
3. To assess blood IgG antibody concentrations against vaccine antigens in
preterm-born infants following booster of routine vaccination with
DTaP5-HB-IPV-Hib as a marker of immune maturation in premature children.
4. To assess blood IgG antibody geometrical mean concentrations in preterm
infants compared to reference values in healthy term infants as known from
literature following primary series and booster of routine vaccination with
DTaP5-HB-IPV-Hib.
5. To assess blood IgG antibody concentrations against vaccine antigens in
preterm-born infants following routine vaccinations with 10-valent pneumococcal
conjugate vaccine after primary series and booster vaccination as a marker of
immune maturation in premature children.
6. To assess blood IgG antibody concentrations against pertussis antigens at 2
months of age (before start of infant immunizations) in preterm-born infants
after maternal Tdap vaccination and in infants whose mother did not receive
maternal Tdap vaccination.
7. To assess blood IgG antibody concentrations against vaccine antigens in
preterm-born infants before start of immunizations and following routine
vaccinations after primary series and booster vaccination, in relation to
maternal antibody concentrations against vaccine antigens.
Proportions of infants with IgG concentrations above the internationally
defined threshold for protection and geometrical mean concentrations will be
compared between preterm infants after maternal Tdap vaccination, preterm
infants whose mothers did not receive Tdap vaccination and reference values in
healthy term infants as known from literature.
Number and repertoire of antigen-specific memory B cells will be compared
between preterm infants after maternal Tdap vaccination, preterm infants whose
mothers did not receive Tdap vaccination and healthy term infants after
maternal Tdap vaccination, who will be recruited for this study.
Background summary
Preterm infants are at increased risk of developing infections early in life
due to a less mature immune system compared to full-term infants. Moreover,
protection by the placental transfer of maternal antibodies in general and
specifically against vaccine antigens has shown to be significantly lower in
very preterm infants (gestational age (GA)< 32 weeks) compared to term infants.
In this study we aim to investigate the immune system development of very
preterm infants. Adequate immune response to vaccination is considered both
clinically important as well as a functional test of the immune system.
However, data on the antibody and Ag-specific memory B cell response to
vaccination in preterm infants are limited.
Longitudinal data on the long-term memory B-cell response (antigen specific
immune maturation) in healthy term infants is also sparse. To compare the
long-term antigen specific memory B-cell response between preterm infants and
healthy controls, Ag-specific memory B cell response to vaccination will be
measured in 25 healthy term infants as well.
Study objective
Primary objective is to study the antibody immune response to routine
vaccinations in very preterm infants (GA<32 weeks). Secondary aim is to study
the immune system more extensively using flow cytometry, ELISA and single cell
transcriptomics to measure development of antigen (Ag)-specific memory B cells
raised in response to vaccination, and by using proteomics, epigenetics, and
microbiome studies.
Study design
Multicenter prospective observational cohort study of 120 very preterm infants
(< GA 32 weeks) and their mothers and 25 healthy term infants. In preterm
infants, antibody response to routine vaccinations as a readout for the
development of the immune system will be measured before start of immunizations
(age 2 months), after primary series (age 6 months) and after booster
vaccination (12 months). To compare the long-term antigen specific memory
B-cell response between preterm infants and healthy controls, Ag-specific
memory B cell response to vaccination will be measured in 25 healthy term
infants after primary series (age 6 months) and after booster vaccination (12
months).
Study burden and risks
The development of the immune system including antibody response to routine
vaccinations will be measured before (age 2 months, in preterm infants) and
after primary and booster vaccination (age 6 and 12 months respectively, in
both preterm and full-term infants). Whenever possible, blood will be collected
at the same time as routine blood draws, but extra blood draws may be needed
for the study. In this case there will be some burden to the infant. For
healthy controls, the study procedures are not part of regular care.
Longitudinal data on the long-term memory B-cell response in children (antigen
specific immune maturation) is sparse. This information is therefore valuable
in itself and for our study essential to compare the long-term antigen specific
memory B-cell response between preterm infants and healthy controls. Previous
studies have shown that maternal pertussis vaccination is highly effective in
preventing pertussis in infants early in life. After implementation of this
maternal pertussis vaccine the national immunization program was adjusted, and
the first vaccination was delayed. However, it is not exactly known how high
the protective antibodies are with this immunization schedule.
To ensure that the burden of blood draw is minimal we will administer sucrose
and apply a topical anesthetic (lidocaine/prilocaine or lidocaine/ tetracaine)
according to local guidelines. Blood volume restrictions will comply with the
recommendations of the European Commission and the World Health Organization
(WHO) guidelines.
There is no direct benefit of participation to the participant. However,
knowledge and insight gained during this study contributes to knowledge on
immune system development of premature infants and may aid to improve vaccine
schedules and protection against vaccine-preventable diseases for preterm
infants in the future.
Given the aim of this study, it can only be performed in children and not in
adults. Since this is an observational, non-interventional study, in which the
response to routine vaccinations will be measured as a proxy for the immune
maturation of premature children, the risk of participating in this study is
considered negligible. The risk of this study procedure (blood draw) is
considered very low.
P. Debyelaan 25
Maastricht 6229HX
NL
P. Debyelaan 25
Maastricht 6229HX
NL
Listed location countries
Age
Inclusion criteria
• Preterm infant born at gestational age less than 32 weeks (whose mothers did
or did not receive a T dap vaccination during pregnancy) OR healthy full-term
infant whose mother received a Tdap vaccination during pregnancy
• Mothers of included preterm infants
•Parents/ guardians must have sufficient understanding of the Dutch language
Exclusion criteria
• Parents/guardians not able or willing to provide informed consent
• Infant with congenital anomaly which are more likely to cause adverse effects
after immunization (for example hemodynamically significant congenital heart
defect)
• Infant with a (possible) HIV infection, immunodeficiency or use of
immunomodulating drugs
• Maternal use of immunosuppressive drugs during pregnancy
• Parental intention not to vaccinate according to the National Immunization
Program
Design
Recruitment
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 |
|---|---|
| Other | Clinical Trials.Gov |
| CCMO | NL80118.068.22 |