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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03383211
Recruitment Status : Active, not recruiting
First Posted : December 26, 2017
Last Update Posted : August 13, 2019
Sponsor:
Collaborators:
Universitatea de Stat de Medicina si Farmacie Nicolae Testemiţanu
Children's National Research Institute
DC-Center for Aids Research (DC-CFAR)
SeqLL, Inc.
Information provided by (Responsible Party):
Ian Toma, MD, PhD, George Washington University

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
HIV Infections Neonatal Infection LTBI - Latent Tuberculosis Infection Immune Tolerance 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.

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Study Type : Observational
Estimated Enrollment : 150 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 : June 16, 2017
Estimated Primary Completion Date : September 1, 2019
Estimated Study Completion Date : June 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Group/Cohort 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




Primary Outcome Measures :
  1. Changes in immune-associated transcripts [ Time Frame: Collection of samples 7-days after BCG vaccination ]
    Identification of transcripts that are differential expressed between groups


Biospecimen Retention:   Samples With DNA
RNA isolated from peripheral blood.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Pregnant women or women of the reproductive age
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Pregnant women, 18-45 years old who consented for participation in the study. All women are managed by the local national healthcare system without any interventions from the research team. The collection of samples is performed by the local trained medical personnel, and the samples are processed in a research laboratory.
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03383211


Locations
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Moldova, Republic of
Clinical Municipal Hospital No. 1
Chisinau, Moldova, Republic of
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 Testemiţanu
Children's National Research Institute
DC-Center for Aids Research (DC-CFAR)
SeqLL, Inc.
Investigators
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Principal Investigator: Ian Toma, MD, PhD George Washington University
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Responsible Party: Ian Toma, MD, PhD, Associate Research Professor, George Washington University
ClinicalTrials.gov Identifier: NCT03383211    
Other Study ID Numbers: GWMDA2017
First Posted: December 26, 2017    Key Record Dates
Last Update Posted: August 13, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Genomic data will be submitted to the NCBI SRA archive
Time Frame: Upon completion of analysis
Access Criteria: NCBI standard access criteria

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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, George Washington University:
RNAseq
Next Generation Sequencing
Transcriptome
Peripheral blood transcripts
Tempus Blood RNA Tubes
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Tuberculosis
Latent Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections