Maternal Determinants of Infant Immunity to Pertussis

Pertussis Clinical Trial

— MADI-02  

Official title:

Maternal Determinants of Infant Immunity to Pertussis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05856396
• Other study ID #: B0762022220909
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: June 1, 2023
• Est. completion date: December 2025

Study information

• Verified date: May 2023
• Source: Centre Hospitalier Universitaire Saint Pierre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The overall objective of the project is to identify the determinants of antibody-mediated immunity in infants born to mothers immunized during pregnancy. Using maternal pertussis immunization as a model, the project will identify key predictors and potential determinants of vaccine responses in pregnant women, of the transfer of maternal antibodies to the newborn and of vaccine responses in infants. A systems biology approach will be used to delineate pre-vaccination and post-vaccination cellular and molecular correlates of the immune response to pertussis immunization in peripheral blood and in breastmilk.

Description:

The overall objective of the project is to identify the determinants of antibody-mediated immunity to pertussis in infants born to mothers immunized during pregnancy. Three specific objectives will be targeted:

1. Determine the impact of pregnancy on the quality of antibody response to pertussis immunization and identify immune predictors of vaccine responses in pregnant and non-pregnant women.

2. Identify immune predictors of the transfer of maternal antibodies to the newborn and the presence of antibody in breastmilk following pertussis immunization during pregnancy.

3. Determine the impact of maternal antibodies on the quality of antibody response to pertussis immunization in infants born to mothers immunized or not immunized during pregnancy and identify immune predictors of vaccine responses in the first months of life.

To reach these objectives, 40 non-pregnant and 80 pregnant women will be recruited into the study and vaccinated with a single dose of a pertussis containing vaccine (Boostrix). Blood samples will be collected from:

• non-pregnant women: before vaccination, and day 1/7/28 and month 5 post-vaccination.

• pregnant women: before vaccination, day 1/7/28 post-vaccination, at delivery, and week 6/12 post-delivery. At week 6/12 post-delivery, breast milk samples will be collected as well.

In addition, infants 2-3 months old born either from mothers who were not vaccinated against pertussis during pregnancy (n=40) or born from mothers who were vaccinated against pertussis during pregnancy (n=80) will be recruited in the study. Infants will be vaccinated with three doses of a pertussis containing vaccine (Hexyon), each one month apart starting from 2-3 months of age. Blood samples will be collected from:

• infants from vaccinated mothers: cord blood, before 1st vaccine dose, day 1 post 1st vaccine dose, before 3rd vaccine dose, and day 28 post 3rd vaccine dose.

• infants from unvaccinated mothers: before 1st vaccine dose, day 1 post 1st vaccine dose, before 3rd vaccine dose, and day 28 post 3rd vaccine dose.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 2 Months to 45 Years

Eligibility

Inclusion Criteria:

• For non-pregnant & pregnant women Age between 18 and 45 years Eligible for Tdap vaccination

• For infants Born to mothers vaccinated or not with Tdap Vaccinated with hexavalent vaccine Age between 2 and 3 months

Exclusion Criteria:

• For pregnant and non-pregnant women

• Inability to understand the nature and extent of the study and the procedures required

• Grade III/IV anemia,

• Acute infection at the time of immunization

• Chronic infections such as Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV) infection, acute toxoplasmosis

• Current or recent use of immunosuppressive drugs

• Active neoplasia

• Other vaccine(s) administered at the same time as Tdap vaccination (wash out of 3 weeks after others vaccinations and 28 days after Tdap vaccination )

• For pregnant women

• Risk of premature delivery or intrauterine growth retardation

• Twin or triplet pregnancies

• For non-pregnant women Last Tdap vaccination < 12 months before

For infants:

• Infants born before 35 weeks of gestation

• Birthweight below 2.5 kg,

• Severe neonatal distress

• Serious congenital abnormalities or congenital infection.

Related Conditions & MeSH terms

• Immunoglobulins
• Maternal-Fetal Relations
• Pertussis
• Vaccination; Infection
• Whooping Cough

Intervention

Biological:
• Boostrix® (Pertussis-containing vaccine)
Boostrix® (Pertussis-containing vaccine) will be administered: in non-pregnant women presenting to the Travel and Vaccine clinic for pertussis immunization only or hospital member staff requiring Tetanus Toxoid (TT)-booster immunisation in Pregnant women between 16 and 29 weeks of gestation.
• Hexyon® (Pertussis-containing vaccine)
Hexyon ® (Hexavalent vaccine) will be proposed in infants at 8, 12 and 16 weeks of life.

Locations

Country	Name	City	State
Belgium	CHU Saint-Pierre	Brussels

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire Saint Pierre	Université Libre de Bruxelles

Country where clinical trial is conducted

Belgium, 

References & Publications (7)

Gunn BM, Alter G. Modulating Antibody Functionality in Infectious Disease and Vaccination. Trends Mol Med. 2016 Nov;22(11):969-982. doi: 10.1016/j.molmed.2016.09.002. Epub 2016 Oct 15. — View Citation

Jennewein MF, Abu-Raya B, Jiang Y, Alter G, Marchant A. Transfer of maternal immunity and programming of the newborn immune system. Semin Immunopathol. 2017 Nov;39(6):605-613. doi: 10.1007/s00281-017-0653-x. Epub 2017 Oct 2. — View Citation

Jennewein MF, Alter G. The Immunoregulatory Roles of Antibody Glycosylation. Trends Immunol. 2017 May;38(5):358-372. doi: 10.1016/j.it.2017.02.004. Epub 2017 Apr 3. — View Citation

Jennewein MF, Goldfarb I, Dolatshahi S, Cosgrove C, Noelette FJ, Krykbaeva M, Das J, Sarkar A, Gorman MJ, Fischinger S, Boudreau CM, Brown J, Cooperrider JH, Aneja J, Suscovich TJ, Graham BS, Lauer GM, Goetghebuer T, Marchant A, Lauffenburger D, Kim AY, Riley LE, Alter G. Fc Glycan-Mediated Regulation of Placental Antibody Transfer. Cell. 2019 Jun 27;178(1):202-215.e14. doi: 10.1016/j.cell.2019.05.044. Epub 2019 Jun 13. — View Citation

Jennewein MF, Kosikova M, Noelette FJ, Radvak P, Boudreau CM, Campbell JD, Chen WH, Xie H, Alter G, Pasetti MF. Functional and structural modifications of influenza antibodies during pregnancy. iScience. 2022 Mar 16;25(4):104088. doi: 10.1016/j.isci.2022.104088. eCollection 2022 Apr 15. — View Citation

Marchant A, Sadarangani M, Garand M, Dauby N, Verhasselt V, Pereira L, Bjornson G, Jones CE, Halperin SA, Edwards KM, Heath P, Openshaw PJ, Scheifele DW, Kollmann TR. Maternal immunisation: collaborating with mother nature. Lancet Infect Dis. 2017 Jul;17(7):e197-e208. doi: 10.1016/S1473-3099(17)30229-3. Epub 2017 Apr 19. — View Citation

Tsang JS. Utilizing population variation, vaccination, and systems biology to study human immunology. Trends Immunol. 2015 Aug;36(8):479-93. doi: 10.1016/j.it.2015.06.005. Epub 2015 Jul 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	IgG titers specific to Bordetella Pertussis Antigens by Enzyme-linked immunosorbent assay (ELISA)	IgG titers specific to Bordetella Pertussis Antigens will be assessed by ELISA: in women (pregnant and non-pregnant) at 28 days post vaccination; in infants (from unvaccinated mothers and mothers vaccinated during pregnancy) at 28 days post third vaccine dose	Day 28 post-vaccination
Primary	IgG titers specific to Bordetella Pertussis Antigens by Enzyme-linked immunosorbent assay (ELISA)	IgG titers specific to Bordetella Pertussis Antigens will be assessed by ELISA: in women vaccinated during pregnancy, at delivery; in umbilical cord blood of infants born to mothers vaccinated during pregnancy	At delivery
Secondary	IgG titers specific to Bordetella Pertussis Antigens by Enzyme-linked immunosorbent assay (ELISA)	IgG titers specific to Bordetella Pertussis Antigens will be assessed by ELISA: in pregnant women (PW): at day of vaccination , day 7 post-vaccination, week 6 and 12 post-delivery; in non-pregnant women (non PW): at day of vaccination, day 7 and Month 5 post-vaccination; in infants (from unvaccinated mothers and mothers vaccinated during pregnancy) at day of first and third vaccine dose	up to 9 month after vaccination
Secondary	CD4+ T cell frequencies specific to Bordetella Pertussis Antigens by flow cytometry	The percentage of CD4+ T cells expressing any of the following biomarkers (CD154, Interferon gamma, IL-2) in response to in vitro stimulation with Bordetella Pertussis Antigens will be measured by flow cytometry: i. in pregnant and non-pregnant women: at day of vaccination, and day 28 post vaccination; ii. in infants (from unvaccinated mothers and mothers vaccinated during pregnancy) at day of first vaccine dose and 28 days after third vaccine dose	up to 9 month after vaccination