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

Completed

• Conditions: HIV Infections; Neonatal Infection; LTBI - Latent Tuberculosis Infection; Immune Tolerance
• Interventions: Other: RNAseq

• Registration Number: NCT03383211
• Lead Sponsor: 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.

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 Timeline

• Study Start: 2017-06-16
• Study First Submitted: 2017-12-19
• Study First Submitted QC: 2017-12-19
• Study First Posted: 2017-12-26
• Primary Completion: 2020-09-01
• Study Completion: 2021-06-30
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-19
• Last Update Posted: 2021-10-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 125

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
HV+/LTBI	RNAseq	Pregnant women diagnosed with HIV and LTBI co-infection. No intervention beyond the standard of care provided for such cohort.
HIV+	RNAseq	Pregnant women diagnosed with HIV infection during pregnancy. No intervention beyond the standard care provided for such cohort.
LTBI	RNAseq	Pregnant women diagnosed with Latent form of TB infection (LTBI). No intervention beyond the standard of care provided for such cohort.
Healthy Control	RNAseq	Healthy pregnant women without HIV or LTBI. No intervention beyond the standard of care provided for such cohort.

Primary Outcome Measures

Name	Time	Method
Changes in immune-associated transcripts	Collection of samples 7-days after BCG vaccination	Identification of transcripts that are differential expressed between groups

Trial Locations

Locations (2)

National Center for Mother and Child Health; 🇲🇩 Chisinau, Moldova, Republic of

Clinical Municipal Hospital No. 1; 🇲🇩 Chisinau, Moldova, Republic of