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

NCT03383211 | Completed

• 1 other identifier: GWMDA2017
• Study Type: observational
• Target: 125
• Locations: 1 country
• Sites: 2

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.

Conditions

HIV Infections; Neonatal Infection; LTBI - Latent Tuberculosis Infection; Immune Tolerance

Keywords

RNAseq; Next Generation Sequencing; Transcriptome; Peripheral blood transcripts; Tempus Blood RNA Tubes

Outcome Measures

Primary Outcomes (1)

• Changes in immune-associated transcripts

  Identification of transcripts that are differential expressed between groups

  Collection of samples 7-days after BCG vaccination

Study Arms (4)

HIV+

Pregnant women diagnosed with HIV infection during pregnancy. No intervention beyond the standard care provided for such cohort.

Other: RNAseq

LTBI

Pregnant women diagnosed with Latent form of TB infection (LTBI). No intervention beyond the standard of care provided for such cohort.

Other: RNAseq

HV+/LTBI

Pregnant women diagnosed with HIV and LTBI co-infection. No intervention beyond the standard of care provided for such cohort.

Other: RNAseq

Healthy Control

Healthy pregnant women without HIV or LTBI. No intervention beyond the standard of care provided for such cohort.

Other: RNAseq

Interventions

RNAseq OTHER

Transcriptome profiling of peripheral blood using RNA sequencing technology

HIV+; HV+/LTBI; Healthy Control; LTBI

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Pregnant women or women of the reproductive age
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• George Washington University: lead
• Universitatea de Stat de Medicina si Farmacie Nicolae Testemiţanu: collaborator
• Children's National Research Institute: collaborator
• DC-Center for Aids Research (DC-CFAR): collaborator
• SeqLL, Inc.: collaborator

Study Sites (2)

Clinical Municipal Hospital No. 1

Chisinau, Moldova

Location

National Center for Mother and Child Health

Chisinau, Moldova

Location

Biospecimen

Retention: SAMPLES WITH DNA

RNA isolated from peripheral blood.

MeSH Terms

Conditions

HIV Infections; Latent Tuberculosis

Interventions

Base Sequence

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Molecular Structure; Biochemical Phenomena; Chemical Phenomena; Genetic Structures; Genetic Phenomena

Study Officials

• Ian Toma, MD, PhD

  George Washington University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Research Professor

Study Record Dates

• First Submitted: December 19, 2017
• First Posted: December 26, 2017
• Study Start: June 16, 2017
• Primary Completion: September 1, 2020
• Study Completion: June 30, 2021
• Last Updated: October 20, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Time Frame: Upon completion of analysis
• Access Criteria: NCBI standard access criteria

Locations

MO (2)