Immune Response to BCG Vaccination in Neonates Born to HIV and LTBI Infected and Non-infected Mothers
Condition: HIV Infections; Neonatal Infection; LTBI - Latent Tuberculosis Infection; Immune Tolerance
MeSH terms: Infections; Communicable Diseases; Tuberculosis; Latent Tuberculosis
Study type: Observational

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.
    

Intervention name(s): RNAseq
Intervention type(s): Other
Intervention description(s): Transcriptome profiling of peripheral blood using RNA sequencing technology
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.
      
Biospecimen description: 
      RNA isolated from peripheral blood.
    
Keywords: RNAseq; Next Generation Sequencing; Transcriptome; Peripheral blood transcripts; Tempus Blood RNA Tubes