Clinical trial NCT03383211: Immune Response to BCG Vaccination in Neonates Born to HIV and LTBI Infected and Non-infected Mothers
Official title: Transcriptomic Profile of the Immune Response to BCG Vaccination in Neonates Born to HIV and LTBI Infected and Non-infected Mothers
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Neonatal Infection
LTBI - Latent Tuberculosis Infection
Immune Tolerance
Keywords: RNAseq
Next Generation Sequencing
Transcriptome
Peripheral blood transcripts
Tempus Blood RNA Tubes
Lead sponsor: George Washington University
Sponsor class: OTHER
Collaborators: name: Universitatea de Stat de Medicina si Farmacie Nicolae Testemiţanu
name: Children's National Research Institute
name: DC-Center for Aids Research (DC-CFAR)
name: SeqLL, Inc.
First posted: 2017-12-26
Enrollment: 125
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

Eligibility 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.

Primary outcomes:
measure: Changes in immune-associated transcripts
timeFrame: Collection of samples 7-days after BCG vaccination
Secondary outcomes:
Other outcomes:
Locations:
city: Chisinau
country: Moldova, Republic of
facility: Clinical Municipal Hospital No. 1
city: Chisinau
country: Moldova, Republic of
facility: National Center for Mother and Child Health
Study officials:
affiliation: George Washington University
name: Ian Toma, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: