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

HIV Infections Clinical Trial

— IMMUNEO  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03383211
• Other study ID #: GWMDA2017
• Status: Completed
• Start date: June 16, 2017
• Est. completion date: June 30, 2021

Study information

• Verified date: October 2021
• Source: George Washington University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: June 30, 2021
• Est. primary completion date: September 1, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• HIV Infections
• Immune Tolerance
• Infections
• Latent Tuberculosis
• LTBI - Latent Tuberculosis Infection
• Neonatal Infection
• Tuberculosis

Intervention

Other:
• RNAseq
Transcriptome profiling of peripheral blood using RNA sequencing technology

Locations

Country	Name	City	State
Moldova, Republic of	Clinical Municipal Hospital No. 1	Chisinau
Moldova, Republic of	National Center for Mother and Child Health	Chisinau

Sponsors (5)

Lead Sponsor	Collaborator
George Washington University	Children's National Research Institute, DC-Center for Aids Research (DC-CFAR), SeqLL, Inc., Universitatea de Stat de Medicina si Farmacie Nicolae Testemitanu

Country where clinical trial is conducted

Moldova, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in immune-associated transcripts	Identification of transcripts that are differential expressed between groups	Collection of samples 7-days after BCG vaccination