Dose-dependent T-cell Dynamics and Cytokine Cascade Following rVSV-ZEBOV Immunization.

BACKGROUND: The recent West African Ebola epidemic led to accelerated efforts to test Ebola vaccine candidates. As part of the World Health Organisation-led VSV Ebola Consortium (VEBCON), we performed a phase I clinical trial investigating rVSV-ZEBOV (a recombinant vesicular stomatitis virus-vectored Ebola vaccine), which has recently demonstrated protection from Ebola virus disease (EVD) in phase III clinical trials and is currently in advanced stages of licensing. So far, correlates of immune protection are incompletely understood and the role of cell-mediated immune responses has not been comprehensively investigated to date. METHODS: We recruited 30 healthy subjects aged 18-55 into an open-label, dose-escalation phase I trial testing three doses of rVSV-ZEBOV (3×105 plaque-forming units (PFU), 3×106 PFU, 2×107 PFU) (ClinicalTrials.gov; NCT02283099). Main study objectives were safety and immunogenicity, while exploratory objectives included lymphocyte dynamics, cell-mediated immunity and cytokine networks, which were assessed using flow cytometry, ELISpot and LUMINEX assay. FINDINGS: Immunization with rVSV-ZEBOV was well tolerated without serious vaccine-related adverse events. Ebola virus-specific neutralizing antibodies were induced in nearly all individuals. Additionally, vaccinees, particularly within the highest dose cohort, generated Ebola glycoprotein (GP)-specific T cells and initiated a cascade of signaling molecules following stimulation of peripheral blood mononuclear cells with Ebola GP peptides. INTERPRETATION: In addition to a benign safety and robust humoral immunogenicity profile, subjects immunized with 2×107 PFU elicited higher cellular immune responses and stronger interlocked cytokine networks compared to lower dose groups. To our knowledge these data represent the first detailed cell-mediated immuneprofile of a clinical trial testing rVSV-ZEBOV, which is of particular interest in light of its potential upcoming licensure as the first Ebola vaccine. VEBCON trial Hamburg, Germany (NCT02283099)

Longitudinal development of antibody responses in COVID-19 patients of different severity with ELISA, peptide, and glycan arrays : an immunological case series

The current COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). A better understanding of its immunogenicity can be important for the development of improved diagnostics, therapeutics, and vaccines. Here, we report the longitudinal analysis of three COVID-19 patients with moderate (1) and mild disease (2 and 3). Antibody serum responses were analyzed using spike glycoprotein enzyme linked immunosorbent assay (ELISA), full-proteome peptide, and glycan microarrays. ELISA immunoglobulin A, G, and M (IgA, IgG, and IgM) signals increased over time for individuals 1 and 2, whereas 3 only showed no clear positive IgG and IgM result. In contrast, peptide microarrays showed increasing IgA/G signal intensity and epitope spread only in the moderate patient 1 over time, whereas early but transient IgA and stable IgG responses were observed in the two mild cases 2 and 3. Glycan arrays showed an interaction of antibodies to fragments of high-mannose and core N-glycans, present on the viral shield. In contrast to protein ELISA, microarrays allow for a deeper understanding of IgA, IgG, and IgM antibody responses to specific epitopes of the whole proteome and glycans of SARS-CoV-2 in parallel. In the future, this may help to better understand and to monitor vaccination programs and monoclonal antibodies as therapeutics

Addressing future food demand in The Gambia: can increased crop productivity and climate change adaptation close the supply–demand gap?

With rising demand for food and the threats posed by climate change, The Gambia faces significant challenges in ensuring sufficient and nutritious food for its population. To address these challenges, there is a need to increase domestic food production while limiting deforestation and land degradation. In this study, we modified the FABLE Calculator, a food and land-use system model, to focus on The Gambia to simulate scenarios for future food demand and increasing domestic food production. We considered the impacts of climate change on crops, the adoption of climate change adaptation techniques, as well as the potential of enhanced fertiliser use and irrigation to boost crop productivity, and assessed whether these measures would be sufficient to meet the projected increase in food demand. Our results indicate that domestic food production on existing cropland will not be sufficient to meet national food demand by 2050, leading to a significant supply–demand gap. However, investments in fertiliser availability and the development of sustainable irrigation infrastructure, coupled with climate change adaptation strategies like the adoption of climate-resilient crop varieties and optimised planting dates, could halve this gap. Addressing the remaining gap will require additional strategies, such as increasing imports, expanding cropland, or prioritising the production of domestic food crops over export crops. Given the critical role imports play in The Gambia’s food supply, it is essential to ensure a robust flow of food imports by diversifying partners and addressing regional trade barriers. Our study highlights the urgent need for sustained investment and policy support to enhance domestic food production and food imports to secure sufficient and healthy food supplies amidst growing demand and climate change challenges

Detection of drug resistant Mycobacterium tuberculosis by high-throughput sequencing of DNA isolated from acid fast bacilli smears

BACKGROUND: Drug susceptibility testing for Mycobacterium tuberculosis (MTB) is difficult to perform in resource-limited settings where Acid Fast Bacilli (AFB) smears are commonly used for disease diagnosis and monitoring. We developed a simple method for extraction of MTB DNA from AFB smears for sequencing-based detection of mutations associated with resistance to all first and several second-line anti-tuberculosis drugs. METHODS: We isolated MTB DNA by boiling smear content in a Chelex solution, followed by column purification. We sequenced PCR-amplified segments of the rpoB, katG, embB, gyrA, gyrB, rpsL, and rrs genes, the inhA, eis, and pncA promoters and the entire pncA gene. RESULTS: We tested our assay on 1,208 clinically obtained AFB smears from Ghana (n = 379), Kenya (n = 517), Uganda (n = 262), and Zambia (n = 50). Coverage depth varied by target and slide smear grade, ranging from 300X to 12000X on average. Coverage of ≥20X was obtained for all targets in 870 (72%) slides overall. Mono-resistance (5.9%), multi-drug resistance (1.8%), and poly-resistance (2.4%) mutation profiles were detected in 10% of slides overall, and in over 32% of retreatment and follow-up cases. CONCLUSION: This rapid AFB smear DNA-based method for determining drug resistance may be useful for the diagnosis and surveillance of drug-resistant tuberculosis

Ecological Study of HIV Infection and Hypertension in Sub-Saharan Africa: Is There a Double Burden of Disease?

An ecological correlation study of the prevalence of hypertension with human immunodeficiency virus (HIV) prevalence in sub-Saharan Africa was conducted to determine the extent to which these conditions coincide at country level. Data on prevalence of hypertension were derived from a systematic search of literature published between 1975 and 2014 with corresponding national estimates on HIV prevalence and antiretroviral therapy (ART) coverage from the Demographic and Health Surveys and the joint United Nations Programme on HIV/AIDS databases. National estimates on gross national income (GNI) and under-five mortality were obtained from the World Bank database. Linear regression analyses using robust standard errors (allowing for clustering at country level) were carried out for associations of age-standardised hypertension prevalence ratios (standardized to rural Uganda’s hypertension prevalence data) with HIV prevalence, adjusted for national indicators, year of study and sex of the study population. In total, 140 estimates of prevalence of hypertension representing 25 nations were sex-and area-matched with corresponding HIV prevalence. A two-fold increase in HIV prevalence was associated with a 9.29% increase in age, sex and study year-adjusted prevalence ratio for hypertension (95% CI 2.0 to 16.5, p = 0.01), which increased to 16.3% (95% CI 9.3 to 21.1) after adjusting for under-five mortality, GNI per capita and ART coverage. Countries with a pronounced burden of HIV may also have an increased burden of non-communicable diseases such as hypertension with potential economic and health systems implications

Discrete populations of isotype-switched memory B lymphocytes are maintained in murine spleen and bone marrow

At present, it is not clear how memory B lymphocytes are maintained over time, and whether only as circulating cells or also residing in particular tissues. Here we describe distinct populations of isotype-switched memory B lymphocytes (Bsm) of murine spleen and bone marrow, identified according to individual transcriptional signature and B cell receptor repertoire. A population of marginal zone-like cells is located exclusively in the spleen, while a population of quiescent Bsm is found only in the bone marrow. Three further resident populations, present in spleen and bone marrow, represent transitional and follicular B cells and B1 cells, respectively. A population representing 10-20% of spleen and bone marrow memory B cells is the only one qualifying as circulating. In the bone marrow, all cells individually dock onto VCAM1+ stromal cells and, reminiscent of resident memory T and plasma cells, are void of activation, proliferation and mobility

Evaluation of sesamum gum as an excipient in matrix tablets

In developing countries modern medicines are often beyond the affordability of the majority of the population. This is due to the reliance on expensive imported raw materials despite the abundance of natural resources which could provide an equivalent or even an improved function. The aim of this study was to investigate the potential of sesamum gum (SG) extracted from the leaves of Sesamum radiatum (readily cultivated in sub-Saharan Africa) as a matrix former. Directly compressed matrix tablets were prepared from the extract and compared with similar matrices of HPMC (K4M) using theophylline as a model water soluble drug. The compaction, swelling, erosion and drug release from the matrices were studied in deionized water, 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) using USP apparatus II. The data from the swelling, erosion and drug release studies were also fitted into the respective mathematical models. Results showed that the matrices underwent a combination of swelling and erosion, with the swelling action being controlled by the rate of hydration in the medium. SG also controlled the release of theophylline similar to the HPMC and therefore may have use as an alternative excipient in regions where Sesamum radiatum can be easily cultivated

Bio-stabilising earthen houses with tannins from locally available resources

This study presents the first-ever comparative evaluation of traditional biostabilisation practices for housing employed in Northern Ghana. Such a comparative evaluation is crucial in understanding and addressing the increased risk of flooding in the region due to a combination of climate change and land use changes. Given the environmental conditions and material availability that shape construction techniques in this area, it is imperative to assess the effectiveness of these practices in mitigating flood risks. The investigation focuses on readily available resources from the Wa and Tamale regions, specifically dawadawa (D), beini (B), and rice husk (R). These biostabilisers were subjected to rigorous testing to assess their efficacy. Earth mortar samples were created using sieved plain local soil (P) with or without the addition of rice husk, which is a local practice, and dawadawa and beini solutions were tested as a water replacement (+wD or +wB, added during material manufacture) or as a surface cover (+coverD or +coverB). The effects are examined in terms of microstructure modifications detected through tannins type and presence, SEM/EDS, water absorption via capillary uptake, and compressive and flexural strength for two different types of application: embedded in the mixture or covering the surface. Overall, solutions containing dawadawa were superior to those containing beini for the tested soil. Both coverD and +coverB decreased the water absorption capacity of the earth mortars and provided almost complete protection for 15 minutes. After three days, all mortars mixed with the dawadawa or beini solutions (P+wD, PR+wD and PR+wB) displayed lower absorption than the P material. Condensed tannins were identified in dawadawa, but only small precipitation in beini and no precipitation in the rice husk. This indicates that dawadawa has a greater degree of polymerisation (compared to rice and beini), developing a polymerisation tannin-iron complex in contact with oxygen from the air, which explains the macrostructure results. SEM/EDS results indicated polymeric condensed tannins and hydrolysable tannins and that complex accumulation and subsequent oxidation are the main reasons for improving water resistance. The laboratory tests, therefore, support the traditional methods of using dawadawa, beini, and, to a lesser extent, rice husk to improve the resilience of earthen houses and structures to water damage and can be used to encourage agro-industry in Northern Ghana to preserve and promote dawadawa and beini resources