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

Transcriptomic Profile of the Immune Response to BCG Vaccination in Neonates Born to HIV and LTBI Infected and Non-infected Mothers

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Neonatal Infection; Immune Tolerance; LTBI - Latent Tuberculosis Infection
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Actual): 125

Contacts and Locations

Study Locations

• Moldova, Republic of
  • Chisinau, Moldova, Republic of
    • Clinical Municipal Hospital No. 1
  • Chisinau, Moldova, Republic of
    • National Center for Mother and Child Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in immune-associated transcripts	Identification of transcripts that are differential expressed between groups	Collection of samples 7-days after BCG vaccination

Collaborators and Investigators

• Sponsor: George Washington University
• Collaborators: Children's National Research Institute; Universitatea de Stat de Medicina si Farmacie Nicolae Testemiţanu; DC-Center for Aids Research (DC-CFAR); SeqLL, Inc.
• Investigators: Principal Investigator: Ian Toma, MD, PhD, George Washington University

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2017
• Primary Completion (Actual): September 1, 2020
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: December 19, 2017
• First Submitted That Met QC Criteria: December 19, 2017
• First Posted (Actual): December 26, 2017

Study Record Updates

• Last Update Posted (Actual): October 20, 2021
• Last Update Submitted That Met QC Criteria: October 19, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: RNAseq; Next Generation Sequencing; Transcriptome; Peripheral blood transcripts; Tempus Blood RNA Tubes
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Latent Infection; Infections; Communicable Diseases; Tuberculosis; Latent Tuberculosis
• Other Study ID Numbers: GWMDA2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Genomic data will be submitted to the NCBI SRA archive
• IPD Sharing Time Frame: Upon completion of analysis
• IPD Sharing Access Criteria: NCBI standard access criteria

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No