IMMUNEO: Immune Response to BCG Vaccination in Neonates Born to HIV and LTBI Infected and Non-infected Mothers

Sponsor
George Washington University (Other)
Overall Status
Completed
CT.gov ID
NCT03383211
Collaborator
Universitatea de Stat de Medicina si Farmacie Nicolae TestemiĊ£anu (Other), Children's National Research Institute (Other), DC-Center for Aids Research (DC-CFAR) (Other), SeqLL, Inc. (Other)
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Study Details

Study Description

Brief Summary

Maternal infections affect the basal immune status of neonates. One of the possible mechanism is the fetomaternal microchimerism, in which some cells and active substances are exchanged bi-directionally between maternal and fetal circulation through placenta. Even in the absence of a direct (vertical) transmission of pathogens to fetuses, certain infections make the neonates more prone to allergies and some adverse events of early vaccinations. We postulate that the basal immune status of neonates born to HIV and LTBI infected mothers is primed by gestational exposure to immunological active molecules, which could results in an altered response to early BCG vaccination. Transcripts expression identified by RNA sequencing are compared between sets of mother-child and their respective umbilical cord blood, and between groups of infected and non-infected pairs.

Condition or Disease Intervention/Treatment Phase
  • Other: RNAseq

Detailed Description

The study is comparing the transcriptomic profiles of maternal peripheral blood with those of the corresponding umbilical cord blood and neonatal peripheral blood pre- and post-BCG vaccination.

For RNA sequencing, the samples are collected in Tempus RNA Blood tubes at 5 time-points (TP): maternal peripheral blood at the time of initial diagnosis with HIV (first OBGYN consultation @ 12-16 weeks of pregnancy - TP1); repeated HIV test in 3rd trimester of pregnancy (34-36 weeks- TP2); umbilical cord blood (after delivery and ligation- TP3); neonates (24 hours after birth and after HBV vaccination, prior to BCG vaccination- TP4); and neonates (7 days after BCG vaccination- TP5).

As an indicator of the inflammatory status, the peripheral blood samples collected at the same TP are stained for serological markers of inflammation, exhaustion, maturation and activation.

An advanced bioinformatics analysis examines the immune-associated transcripts in RNAseq samples to assess the V(D)J recombination of T-cell and B-cell receptors along with immune-associated SNPs.

The main goal of the study is to identify in umbilical cord blood the genomic biomarkers of the neonatal basal immune status for guiding an optimal BCG immunization protocol for such neonates and to avoid potential adverse events after vaccination.

Study Design

Study Type:
Observational
Actual Enrollment :
125 participants
Observational Model:
Case-Control
Time Perspective:
Prospective
Official Title:
Transcriptomic Profile of the Immune Response to BCG Vaccination in Neonates Born to HIV and LTBI Infected and Non-infected Mothers
Actual Study Start Date :
Jun 16, 2017
Actual Primary Completion Date :
Sep 1, 2020
Actual Study Completion Date :
Jun 30, 2021

Arms and Interventions

Arm Intervention/Treatment
HIV+

Pregnant women diagnosed with HIV infection during pregnancy. No intervention beyond the standard care provided for such cohort.

Other: RNAseq
Transcriptome profiling of peripheral blood using RNA sequencing technology

LTBI

Pregnant women diagnosed with Latent form of TB infection (LTBI). No intervention beyond the standard of care provided for such cohort.

Other: RNAseq
Transcriptome profiling of peripheral blood using RNA sequencing technology

HV+/LTBI

Pregnant women diagnosed with HIV and LTBI co-infection. No intervention beyond the standard of care provided for such cohort.

Other: RNAseq
Transcriptome profiling of peripheral blood using RNA sequencing technology

Healthy Control

Healthy pregnant women without HIV or LTBI. No intervention beyond the standard of care provided for such cohort.

Other: RNAseq
Transcriptome profiling of peripheral blood using RNA sequencing technology

Outcome Measures

Primary Outcome Measures

  1. Changes in immune-associated transcripts [Collection of samples 7-days after BCG vaccination]

    Identification of transcripts that are differential expressed between groups

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 45 Years
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:

Pregnant women, 18-45 years old, capable of reading and understanding the informed consent and the purpose of the study The newborns of the enrolled pregnant women. Women of reproductive age with or without HIV and LTBI infections

Exclusion Criteria:

Pregnant women younger than 18 years or older than 45 years of age Pregnant women and infants with known genetic abnormalities, including primary immunodeficiencies; or receiving immunosuppressive therapy; Infants infected in utero, perinatally, or neonatally with hepatitis B virus, Treponema pallidum (syphilis), Toxoplasma gondii, rubella virus, cytomegalovirus, or herpes simplex virus.

Pregnant women with known history of alcohol or drug abuse, cancer diagnosis and treatment with chemotherapeutic agents, radiation.

Pregnant women with history of organ transplantation.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Clinical Municipal Hospital No. 1 Chisinau Moldova, Republic of
2 National Center for Mother and Child Health Chisinau Moldova, Republic of

Sponsors and Collaborators

  • George Washington University
  • Universitatea de Stat de Medicina si Farmacie Nicolae TestemiĊ£anu
  • Children's National Research Institute
  • DC-Center for Aids Research (DC-CFAR)
  • SeqLL, Inc.

Investigators

  • Principal Investigator: Ian Toma, MD, PhD, George Washington University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Ian Toma, MD, PhD, Associate Research Professor, George Washington University
ClinicalTrials.gov Identifier:
NCT03383211
Other Study ID Numbers:
  • GWMDA2017
First Posted:
Dec 26, 2017
Last Update Posted:
Oct 20, 2021
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Ian Toma, MD, PhD, Associate Research Professor, George Washington University
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 20, 2021