Patterns and cofactors of polyfunctional mycobacteria-specific T cell response restoration following 6-month antiretroviral treatment in children living with HIV.

Background: Despite immune restoration after initiation of antiretroviral treatment (ART), the risk of tuberculosis (TB) persists in children living with HIV (CLHIV). We determined patterns of immune restoration of mycobacteria-specific T cells following ART in CLHIV.

Methods: CD4 and CD8 T cell activation and memory phenotype and functional profiles before and 6 months after ART were evaluated in peripheral blood mononuclear cells (PBMCs) from CLHIV enrolled in the PUSH study (NCT02063880) in Nairobi, Kenya.

Activation-Induced Marker Expression Identifies -Specific CD4 T Cells in a Cytokine-Independent Manner in HIV-Infected Individuals with Latent Tuberculosis.

HIV infection is a significant risk factor for reactivation of latent infection (LTBI) and progression to active tuberculosis disease, yet the mechanisms whereby HIV impairs T cell immunity to have not been fully defined. Evaluation of -specific CD4 T cells is commonly based on IFN-γ production, yet increasing evidence indicates the immune response to is heterogeneous and encompasses IFN-γ-independent responses. We hypothesized that upregulation of surface activation-induced markers (AIM) would facilitate detection of human -specific CD4 T cells in a cytokine-independent manner in HIV-infected and HIV-uninfected individuals with LTBI.

A High Throughput Whole Blood Assay for Analysis of Multiple Antigen-Specific T Cell Responses in Human Infection.

Antigen-specific CD4 and CD8 T cells are important components of the immune response to , yet little information is currently known regarding how the breadth, specificity, phenotype, and function of -specific T cells correlate with infection outcome in humans. To facilitate evaluation of human -specific T cell responses targeting multiple different Ags, we sought to develop a high throughput and reproducible T cell response spectrum assay requiring low blood sample volumes. We describe here the optimization and standardization of a microtiter plate-based, diluted whole blood stimulation assay utilizing overlapping peptide pools corresponding to a functionally diverse panel of 60 Ags.

Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease.

Unlabelled: Our understanding of mechanisms underlying progression from Mycobacterium tuberculosis infection to pulmonary tuberculosis disease in humans remains limited. To define such mechanisms, we followed M. tuberculosis-infected adolescents longitudinally.

A blood RNA signature for tuberculosis disease risk: a prospective cohort study.

Background: Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic. We aimed to assess whether global gene expression measured in whole blood of healthy people allowed identification of prospective signatures of risk of active tuberculosis disease.

Methods: In this prospective cohort study, we followed up healthy, South African adolescents aged 12-18 years from the adolescent cohort study (ACS) who were infected with M tuberculosis for 2 years.

The novel tuberculosis vaccine, AERAS-402, is safe in healthy infants previously vaccinated with BCG, and induces dose-dependent CD4 and CD8T cell responses.

Background: Efforts to reduce risk of tuberculosis disease in children include development of effective vaccines. Our aim was to test safety and immunogenicity of the new adenovirus 35-vectored tuberculosis vaccine candidate AERAS-402 in infants, administered as a boost following a prime with the Bacille Calmette-Guerin vaccine.

Methods: In a phase 1 randomised, double-blind, placebo-controlled, dose-escalation trial, BCG-vaccinated infants aged 6-9 months were sequentially assigned to four study groups, then randomized to receive an increasing dose-strength of AERAS-402, or placebo.

Maturation of innate responses to mycobacteria over the first nine months of life.

Newborns and young infants are particularly susceptible to infections, including Mycobacterium tuberculosis. Further, immunogenicity of vaccines against tuberculosis and other infectious diseases appears suboptimal early in life compared with later in life. We hypothesized that developmental changes in innate immunity would underlie these observations.