COVID-19NESTNCT05429047
Priming of the NEonatal Immune System by Transfer of Maternal Immunity
An observational study of COVID-19 and Maternal Vaccine Exposure, run by Hannover Medical School at 1 site in Germany.
Trial summary
Newborn babies and infants are susceptible to infections as their immune system is still immature. Maternal immune factors for example antibodies and immune cells mitigate this vulnerability. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- COVID-19, Maternal Vaccine Exposure, Respiratory Infections in Children
- What is being tested?
- Tozinameran, COVID-19 and No SARS-CoV-2 exposure
- Type of treatment
- Vaccines
- How many people
- 560 participants
- Where
- 1 siteGermany
- Study dates
- 7 Jun 2022to 1 Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Pregnant women recruited from the Department of Obstetrics and Gynecology, Hannover Medical School
Who may be able to join
- For mothers:
- ≥ 18 years
- Informed Consent
- For children:
- Informed Consent of the parents
Who cannot join
- During pregnancy:
- Premature rupture of membranes (>48h before delivery)
- Preterm Birth (<32+0 weeks of pregnancy)
- Preeclampsia, HELLP syndrome and Eclampsia
- Twin-to-twin transfusion syndrome
- Hydrops fetalis
Show all 18Show fewer
- Oncological disease of the mother
- Immunodeficiency, autoimmune or immunological disorder of the mother
- Further health conditions of mother or fetus that may influence the results of the study according to the opinion of the study team
- In children after delivery:
- Delivery >48h after rupture of membranes
- Perinatal asphyxia (APGAR score at 10 minutes: < 5 and/or blood acidosis (fetal umbilical artery pH: < 7.0, arterial base deficit ≥ 12 mmol/L))
- High flow therapy or non-invasive or invasive ventilation after birth
- Treatment with vasopressors or inotropes after birth
- Treatment with intravenous antibiotics after birth
- Neonatal jaundice with need for an exchange transfusion
- Postnatal need for blood transfusions
- Further health conditions of the child that may influence the results of the study according to the opinion of the study team
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
Hannover Medical School (Medizinische Hochschule Hannover, MHH)
Hanover, Lower Saxony, 30625
Maximilian PDY Krafft, +495115329730, krafft.maximilian@mh-hannover.de
About this study
Newborn babies and infants are susceptible to infections as their immune system is still immature. Maternal immune factors for example antibodies and immune cells mitigate this vulnerability. They are transferred from mother to child via the placenta during pregnancy or by breast milk after birth and provide protection against infectious diseases.
In the case of SARS-CoV-2 it has already been shown that specific antibodies are transferred from mother to children after infection or vaccination during pregnancy. However, to this date it is not known how long such an antibody-mediated protection lasts in children and if this "passive" immunity actually protects infants from SARS-CoV-2 infection in the first months of life.
Read more
In general, there is still little knowledge about the influence of maternal infections during pregnancy, transfer of maternal immune factors to the child and development of the child's immune system and health in the first months of life.
Here, the investigators aim to study transferred immunity (i.e. specific antibodies) against SARS-CoV-2 in children of mothers who received a SARS-CoV-2 vaccination during pregnancy or had a SARS-CoV-2 infection during pregnancy with mothers not exposed or exposed before pregnancy.
In addition, the investigators will comprehensively characterize the development of the cellular immune system in the first year of life (umbilical cord blood, age 6 and 12 months) to explore how maternal exposure to infectious diseases or vaccines influences the development of the immune system of the newborn infant.
Read the detailed description
Pregnant women are at increased risk of severe SARS-CoV-2 infections including ARDS and multi-organ failure and increased risk of miscarriages or premature birth. Although pregnant women were not included in market authorization studies, inoculation with mRNA based vaccines is now recommended in Germany.
Vertical transmission rate of SARS-CoV-2 of infected mothers is < 5% and newborns present in the majority of cases with mild symptoms only. Overall, morbidity and mortality of SARS-CoV-2 infections in childhood are significantly lower in children than adults however it is higher in young infants in the first year of life. Further research into the disease burden of SARS-CoV-2 in neonates and young infants and preventative strategies regarding maternal vaccination strategies is therefore urgently needed.
Pregnant women show robust antibody responses to both mRNA vaccines as well as infection including IgG against spike protein, neutralizing antibodies and spike-specific T cell responses. Both spike-protein IgG as well as neutralizing antibodies can be found in cord blood after vaccination and antibody levels can be detected in the child for up to at least 2-3 months. Equally, vaccination of lactating mothers results in transfer of spike-protein reactive secretory IgA and T cells.
Although there is generally good proof of passive transfer of antibodies to the unborn child and neonate transplacentally and via mother's milk, many open question remain. It remains unclear, which vaccination regime results in optimal transfer to the newborn child, if vaccination shows improved protection to infection or if general boostering should be recommended for all women in the second trimenon irrespective of previous vaccination or infection history. Additionally, most studies showing vertical transfer of antibodies to the newborn child have been done with small numbers of mother-child dyads and without clinical follow-up regarding risk of SARS-CoV-2 infection in the first year of life.
Furthermore, it remains unexplored if maternal SARS-CoV2 infection or vaccination during pregnancy shapes the fetus immune system with long-lasting effects. Maternal infections can shape the neonatal immune system even if the fetus remains uninfected. Similar effects have been suggested for maternal vaccination during pregnancy. Studies investigating the effect of maternal SARS-CoV-2 infection during pregnancy on uninfected neonates show mild cytokine response in the neonate as measured in cord blood but no major alterations to lymphocyte subsets and T cell repertoire. However, comprehensive immunophenotyping of the newborns' cellular immune system after either SARS-CoV-2 infection and/ or vaccination during pregnancy with clinical follow-up of the children in the first year of life has not been done yet.
With this study, the investigators aim to examine the antibody response in mother-child dyads after either SARS-CoV-2 vaccination or infection during pregnancy compared to mothers with SARS-CoV-2 vaccination or infection before pregnancy. Antibody titers will be measured in the blood of children and mothers as well as mother's milk.
This data will be combined with comprehensive phenotyping of the cellular immune cells, microbiome analysis and data regarding the child's clinical outcome regarding respiratory infections in the first year of life.
- Being tested
- Tozinameran, COVID-19, No SARS-CoV-2 exposure
- Keywords
- first year of life, development of the immune system, antibody transfer via placenta, breast milk
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TozinameranBiological
Tozinameran during pregnancy
COVID-19Other
SARS-CoV-2 infection during pregnancy
No SARS-CoV-2 exposureOther
No SARS-CoV-2 exposure during pregnancy
| Study group | Role | What they receive |
|---|---|---|
| SARS-CoV-2 vaccine during pregnancy | Pregnant women who received a vaccine against SARS-CoV-2 during pregnancy and their children Receives: Biological: Tozinameran | |
| SARS-CoV-2 infection during pregnancy | Pregnant women who were diagnosed with a SARS-CoV-2 infection during pregnancy and their children Receives: Other: COVID-19 | |
| SARS-CoV-2 vaccine or infection before pregnancy | Pregnant women who neither received a COVID-19 vaccine nor were diagnosed with COVID-19 during their pregnancy but had either a COVID-19 vaccine or infection before pregnancy and their children Receives: Other: No SARS-CoV-2 exposure | |
| No exposure | Pregnant women, who were never exposed to a SARS-CoV-2 vaccine or infection until the birth and their children Receives: Other: No SARS-CoV-2 exposure |
What is being measured
The primary outcome is the main question the study is designed to answer.
anti-SARS-CoV-2 IgG Titer and neutralizing antibody titers in cord blood
Measured: at delivery
Secondary outcomes (9)
anti-SARS-CoV-2 IgG titer and neutralizing antibody titers in maternal blood
Measured: at delivery, 6 months after delivery, 12 months after delivery
anti-SARS-CoV-2 IgG titer and neutralizing antibody titers in peripheral blood of the child
Measured: at 6 months of life, at 12 months of life
anti-SARS-CoV-2 IgG/IgA titer and neutralizing antibody titers in breast milk
Measured: first week after delivery, 6 month after delivery
SARS-CoV-2 specific T cells in cord blood
Measured: at delivery
SARS-CoV-2 specific T cells immunity in maternal blood
Measured: at delivery
SARS-CoV-2 specific T cells in peripheral blood of the child
Measured: at 6 months of life, at 12 months of life
SARS-CoV-2 specific T cells in breast milk
Measured: first week after delivery, 6 month after delivery
total IgG in cord blood and maternal blood
Measured: at delivery
COVID-19 infection rate in children
Measured: first year of life
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2022
- Study start7 Jun 2022
- Primary completion1 Apr 2023 (estimated)
- Study completion1 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 560 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hannover Medical School
- Sponsor type
- University, hospital or other
- Collaborators
- Else Kröner Fresenius Foundation
- Responsible party
- Sponsor
- Investigators
- Gesine Hansen, Prof. Dr., Principal investigator, Hannover Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05429047
- Sponsor's protocol ID
- NEST
- Acronym
- NEST
- Status last verified
- Jul 2022
- First submitted
- 10 Jun 2022
- Last updated
- 7 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Priming of the NEonatal Immune System by Transfer of Maternal Immunity
- ClinicalTrials.gov ID
- NCT05429047
- Acronym / sponsor ID
- NEST / NEST
- Keywords
- first year of life, development of the immune system, antibody transfer via placenta, breast milk
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 560 participants (estimated)
- Lead sponsor
- Hannover Medical SchoolUniversity, hospital or other
- Collaborators
- Else Kröner Fresenius Foundation
- Study start
- 7 Jun 2022 (actual)
- Primary completion
- 1 Apr 2023 (estimated)
- Study completion
- 1 Dec 2023 (estimated)
- First posted
- 23 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Newborn babies and infants are susceptible to infections as their immune system is still immature. Maternal immune factors for example antibodies and immune cells mitigate this vulnerability. They are transferred from mother to child via the placenta during pregnancy or by breast milk after birth and provide protection against infectious diseases.
In the case of SARS-CoV-2 it has already been shown that specific antibodies are transferred from mother to children after infection or vaccination during pregnancy. However, to this date it is not known how long such an antibody-mediated protection lasts in children and if this "passive" immunity actually protects infants from SARS-CoV-2 infection in the first months of life.
In general, there is still little knowledge about the influence of maternal infections during pregnancy, transfer of maternal immune factors to the child and development of the child's immune system and health in the first months of life.
Here, the investigators aim to study transferred immunity (i.e. specific antibodies) against SARS-CoV-2 in children of mothers who received a SARS-CoV-2 vaccination during pregnancy or had a SARS-CoV-2 infection during pregnancy with mothers not exposed or exposed before pregnancy.
In addition, the investigators will comprehensively characterize the development of the cellular immune system in the first year of life (umbilical cord blood, age 6 and 12 months) to explore how maternal exposure to infectious diseases or vaccines influences the development of the immune system of the newborn infant.
Detailed description
Pregnant women are at increased risk of severe SARS-CoV-2 infections including ARDS and multi-organ failure and increased risk of miscarriages or premature birth. Although pregnant women were not included in market authorization studies, inoculation with mRNA based vaccines is now recommended in Germany.
Vertical transmission rate of SARS-CoV-2 of infected mothers is < 5% and newborns present in the majority of cases with mild symptoms only. Overall, morbidity and mortality of SARS-CoV-2 infections in childhood are significantly lower in children than adults however it is higher in young infants in the first year of life. Further research into the disease burden of SARS-CoV-2 in neonates and young infants and preventative strategies regarding maternal vaccination strategies is therefore urgently needed.
Pregnant women show robust antibody responses to both mRNA vaccines as well as infection including IgG against spike protein, neutralizing antibodies and spike-specific T cell responses. Both spike-protein IgG as well as neutralizing antibodies can be found in cord blood after vaccination and antibody levels can be detected in the child for up to at least 2-3 months. Equally, vaccination of lactating mothers results in transfer of spike-protein reactive secretory IgA and T cells.
Although there is generally good proof of passive transfer of antibodies to the unborn child and neonate transplacentally and via mother's milk, many open question remain. It remains unclear, which vaccination regime results in optimal transfer to the newborn child, if vaccination shows improved protection to infection or if general boostering should be recommended for all women in the second trimenon irrespective of previous vaccination or infection history. Additionally, most studies showing vertical transfer of antibodies to the newborn child have been done with small numbers of mother-child dyads and without clinical follow-up regarding risk of SARS-CoV-2 infection in the first year of life.
Furthermore, it remains unexplored if maternal SARS-CoV2 infection or vaccination during pregnancy shapes the fetus immune system with long-lasting effects. Maternal infections can shape the neonatal immune system even if the fetus remains uninfected. Similar effects have been suggested for maternal vaccination during pregnancy. Studies investigating the effect of maternal SARS-CoV-2 infection during pregnancy on uninfected neonates show mild cytokine response in the neonate as measured in cord blood but no major alterations to lymphocyte subsets and T cell repertoire. However, comprehensive immunophenotyping of the newborns' cellular immune system after either SARS-CoV-2 infection and/ or vaccination during pregnancy with clinical follow-up of the children in the first year of life has not been done yet.
With this study, the investigators aim to examine the antibody response in mother-child dyads after either SARS-CoV-2 vaccination or infection during pregnancy compared to mothers with SARS-CoV-2 vaccination or infection before pregnancy. Antibody titers will be measured in the blood of children and mothers as well as mother's milk.
This data will be combined with comprehensive phenotyping of the cellular immune cells, microbiome analysis and data regarding the child's clinical outcome regarding respiratory infections in the first year of life.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| SARS-CoV-2 vaccine during pregnancy | – | Biological: TozinameranPregnant women who received a vaccine against SARS-CoV-2 during pregnancy and their children |
| SARS-CoV-2 infection during pregnancy | – | Other: COVID-19Pregnant women who were diagnosed with a SARS-CoV-2 infection during pregnancy and their children |
| SARS-CoV-2 vaccine or infection before pregnancy | – | Other: No SARS-CoV-2 exposurePregnant women who neither received a COVID-19 vaccine nor were diagnosed with COVID-19 during their pregnancy but had either a COVID-19 vaccine or infection before pregnancy and their children |
| No exposure | – | Other: No SARS-CoV-2 exposurePregnant women, who were never exposed to a SARS-CoV-2 vaccine or infection until the birth and their children |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Pregnant women recruited from the Department of Obstetrics and Gynecology, Hannover Medical School
Key inclusion criteria (5 listed)
- ≥ 18 years
- Informed Consent
- Informed Consent of the parents
Key exclusion criteria (18 listed)
- Premature rupture of membranes (>48h before delivery)
- Preterm Birth (<32+0 weeks of pregnancy)
- Preeclampsia, HELLP syndrome and Eclampsia
- Twin-to-twin transfusion syndrome
- Hydrops fetalis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TozinameranTozinameran during pregnancy | Biological | SARS-CoV-2 vaccine during pregnancy |
| COVID-19SARS-CoV-2 infection during pregnancy | Other | SARS-CoV-2 infection during pregnancy |
| No SARS-CoV-2 exposureNo SARS-CoV-2 exposure during pregnancy | Other | No exposure, SARS-CoV-2 vaccine or infection before pregnancy |
Primary outcome
anti-SARS-CoV-2 IgG Titer and neutralizing antibody titers in cord blood
Time frame: at delivery
9 secondary outcomes
anti-SARS-CoV-2 IgG titer and neutralizing antibody titers in maternal blood
Time frame: at delivery, 6 months after delivery, 12 months after delivery
anti-SARS-CoV-2 IgG titer and neutralizing antibody titers in peripheral blood of the child
Time frame: at 6 months of life, at 12 months of life
anti-SARS-CoV-2 IgG/IgA titer and neutralizing antibody titers in breast milk
Time frame: first week after delivery, 6 month after delivery
SARS-CoV-2 specific T cells in cord blood
Time frame: at delivery
SARS-CoV-2 specific T cells immunity in maternal blood
Time frame: at delivery
SARS-CoV-2 specific T cells in peripheral blood of the child
Time frame: at 6 months of life, at 12 months of life
SARS-CoV-2 specific T cells in breast milk
Time frame: first week after delivery, 6 month after delivery
total IgG in cord blood and maternal blood
Time frame: at delivery
COVID-19 infection rate in children
Time frame: first year of life
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gesine Hansen, Prof. Dr. principal investigator
Hannover Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COVID-19 and Maternal Vaccine Exposure, run by Hannover Medical School at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Maximilian PDY Krafft (+49 511 532 9730, krafft.maximilian@mh-hannover.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
anti-SARS-CoV-2 IgG Titer and neutralizing antibody titers in cord blood (time frame: at delivery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2022.