SATVI - after 10 years closing in on a new and better vaccine to prevent tuberculosis

The vision of the South African Tuberculosis Vaccine Initiative (SATVI) (www.satvi.uct.ac.za) is ‘A World Without TB’ and our mission is ‘Innovative and high-quality TB vaccine research in Africa, to impact the global epidemic’. Over the last 10 years, our focus has been twofold: first, clinical trials of BCG and of new candidate vaccines, and second, complementary research that addresses critical questions in TB vaccine development. SATVI is now widely regarded as the leading TB vaccine clinical research site in the world

Report of the JRC’s Descriptor 1 workshop to support the review of the Commission Decision 2010/477/EU concerning MSFD criteria for assessing Good Environmental Status

The MSFD workshop on biodiversity (MSFD D1), held in Ispra JRC (7th-9th of September 2015) aimed to provide clear proposals and conclusions on some of the outstanding issues identified in the D1 review manual (May 2015 consultation version: https://circabc.europa.eu/w/browse/46d2b7ba-d2fd-4b3c-9eaf-18c7cb702b53) in the broader context of support to the review of Commission Decision 2010/477/EU. This report is complementing the Commission Decision 2010/477/EU review manual (JRC96521) and presents the result of the scientific and technical review concluding phase 1 of the review of the Commission Decision 2010/477/EU in relation to Descriptor 1. The review has been carried out by the EC JRC together with experts nominated by EU Member States, and has considered contributions from the GES Working Group in accordance with the roadmap set out in the MSFD implementation strategy (agreed on at the 11th CIS MSCG meeting). The main issues addressed and tackled in this workshop’s report are: - Common lists of elements for the biodiversity assessments (species & habitats) o Review of the “Biological Features” in Table 1 in the MSFD Annex III in relation to D1 requirements o Review of the “Habitat Types” entries in Table 1 in the MSFD Annex III in relation to D1 requirements - Selection/deselection criteria for the inclusion of species and habitats in a group - Updated criteria and indicators for D1 - Habitat/Bird Directives, WFD, Common Fisheries Policy and D1 o Use of species and habitats for the MSFD needs that are already included in other legislation and agreements o Links between status classification approaches (FCS vs GES, GEcS vs GES) - Streamlining of assessments, including scales of assessments - Cross-cutting issues related to D1 implementation o Aggregation rules within D1 criteria/indicators o Final GES integration across descriptors assessments Steps forward and technical needs for D1.JRC.H.1-Water Resource

Association of human TLR1 and TLR6 deficiency with altered immune responses to BCG vaccination in South African infants

The development of effective immunoprophylaxis against tuberculosis (TB) remains a global priority, but is hampered by a partially protective Bacillus Calmette-Guérin (BCG) vaccine and an incomplete understanding of the mechanisms of immunity to Mycobacterium tuberculosis. Although host genetic factors may be a primary reason for BCG's variable and inadequate efficacy, this possibility has not been intensively examined. We hypothesized that Toll-like receptor (TLR) variation is associated with altered in vivo immune responses to BCG. We examined whether functionally defined TLR pathway polymorphisms were associated with T cell cytokine responses in whole blood stimulated ex vivo with BCG 10 weeks after newborn BCG vaccination of South African infants. In the primary analysis, polymorphism TLR6_C745T (P249S) was associated with increased BCG-induced IFN-γ in both discovery (n = 240) and validation (n = 240) cohorts. In secondary analyses of the combined cohort, TLR1_T1805G (I602S) and TLR6_G1083C (synonymous) were associated with increased IFN-γ, TLR6_G1083C and TLR6_C745T were associated with increased IL-2, and TLR1_A1188T was associated with increased IFN-γ and IL-2. For each of these polymorphisms, the hypo-responsive allele, as defined by innate immunity signaling assays, was associated with increased production of TH1-type T cell cytokines (IFN-γ or IL-2). After stimulation with TLR1/6 lipopeptide ligands, PBMCs from TLR1/6-deficient individuals (stratified by TLR1_T1805G and TLR6_C745T hyporesponsive genotypes) secreted lower amounts of IL-6 and IL-10 compared to those with responsive TLR1/6 genotypes. In contrast, no IL-12p70 was secreted by PBMCs or monocytes. These data support a mechanism where TLR1/6 polymorphisms modulate TH1 T-cell polarization through genetic regulation of monocyte IL-10 secretion in the absence of IL-12. These studies provide evidence that functionally defined innate immune gene variants are associated with the development of adaptive immune responses after in vivo vaccination against a bacterial pathogen in humans. These findings could potentially guide novel adjuvant vaccine strategies as well as have implications for IFN-γ-based diagnostic testing for TB

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. We collected blood samples from study participants every 6 months and monitored the adolescents for progression to tuberculosis disease. A prospective signature of risk was derived from whole blood RNA sequencing data by comparing participants who developed active tuberculosis disease (progressors) with those who remained healthy (matched controls). After adaptation to multiplex quantitative real-time PCR (qRT-PCR), the signature was used to predict tuberculosis disease in untouched adolescent samples and in samples from independent cohorts of South African and Gambian adult progressors and controls. Participants of the independent cohorts were household contacts of adults with active pulmonary tuberculosis disease. FINDINGS: Between July 6, 2005, and April 23, 2007, we enrolled 6363 participants from the ACS study and 4466 from independent South African and Gambian cohorts. 46 progressors and 107 matched controls were identified in the ACS cohort. A 16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 66·1% (95% CI 63·2-68·9) and a specificity of 80·6% (79·2-82·0) in the 12 months preceding tuberculosis diagnosis. The risk signature was validated in an untouched group of adolescents (p=0·018 for RNA sequencing and p=0·0095 for qRT-PCR) and in the independent South African and Gambian cohorts (p values <0·0001 by qRT-PCR) with a sensitivity of 53·7% (42·6-64·3) and a specificity of 82·8% (76·7-86) in the 12 months preceding tuberculosis. INTERPRETATION: The whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease. FUNDING: Bill & Melinda Gates Foundation, the National Institutes of Health, Aeras, the European Union, and the South African Medical Research Council

Broadcasting from the field: enabling student-led investigations by distance

We developed a method of enabling environmental science students to conduct a student-led field investigation with academics who broadcast live from the field in conjunction with interactive voting widgets. We have been running these ‘fieldcasts’ for the last five years but now reflect on how they could be useful more broadly as a result of the covid-19 pandemic. Here we describe the approach which uses a framework of fixed and flexible components that takes students through the process of conducting a field investigation. We reflect on its flexibility for new sites and presenters as well as how it could work with socially distanced presenters and technical support

The Novel Tuberculosis Vaccine, AERAS-402, Induces Robust and Polyfunctional CD4+ and CD8+ T Cells in Adults

Rationale: AERAS-402 is a novel tuberculosis vaccine designed to boost immunity primed by bacillus Calmette-Guérin (BCG), the only licensed vaccine