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.

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Key information

Conditions

HIV Infections Actinomycetales Infections Bacterial Infections Bacterial Infections and Mycoses Blood-Borne Infections Communicable Diseases Genital Diseases Gram-Positive Bacterial Infections Immune System Diseases Immune Tolerance Immunologic Deficiency Syndromes Infections LTBI - Latent Tuberculosis Infection Latent Infection Latent Tuberculosis Lentivirus Infections Mycobacterium Infections Neonatal Infection RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Tuberculosis Urogenital Diseases Virus Diseases

Age range

18 year–45 year

Sex eligibility

Female

Study type

Observational

Primary location

Clinical Municipal Hospital No. 1, Chisinau, Moldova

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

RNAseq

Other

Transcriptome profiling of peripheral blood using RNA sequencing technology

Primary outcomes

Changes in immune-associated transcripts

Time frame: Collection of samples 7-days after BCG vaccination

Identification of transcripts that are differential expressed between groups

Sponsors and collaborators

Lead sponsor

George Washington University

Other

Collaborators

Children's National Research Institute
DC-Center for Aids Research (DC-CFAR)
SeqLL, Inc.
Universitatea de Stat de Medicina si Farmacie Nicolae Testemiţanu

Registry information

Official study title

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

Acronym: IMMUNEO

Important dates

Study start: 2017
Primary completion: 2020
Study completion: 2021
First posted: Dec 26, 2017
Registry last updated: Oct 20, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed