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Trichuris trichiura is a parasite that infects 500 million people worldwide, leading to colitis, growth retardation and Trichuris dysentery syndrome. There are no licensed vaccines available to prevent Trichuris infection and current treatments are of limited efficacy. Trichuris infections are linked to poverty, reducing children's educational performance and the economic productivity of adults. We employed a systematic, multi-stage process to identify a candidate vaccine against trichuriasis based on the incorporation of selected T-cell epitopes into virus-like particles. We conducted a systematic review to identify the most appropriate in silico prediction tools to predict histocompatibility complex class II (MHC-II) molecule T-cell epitopes. These tools were used to identify candidate MHC-II epitopes from predicted ORFs in the Trichuris genome, selected using inclusion and exclusion criteria. Selected epitopes were incorporated into Hepatitis B core antigen virus-like particles (VLPs). Bone marrow-derived dendritic cells and bone marrow-derived macrophages responded in vitro to VLPs irrespective of whether the VLP also included T-cell epitopes. The VLPs were internalized and co-localized in the antigen presenting cell lysosomes. Upon challenge infection, mice vaccinated with the VLPs+T-cell epitopes showed a significantly reduced worm burden, and mounted Trichuris-specific IgM and IgG2c antibody responses. The protection of mice by VLPs+T-cell epitopes was characterised by the production of mesenteric lymph node (MLN)-derived Th2 cytokines and goblet cell hyperplasia. Collectively our data establishes that a combination of in silico genome-based CD4+ T-cell epitope prediction, combined with VLP delivery, offers a promising pipeline for the development of an effective, safe and affordable helminth vaccine.

[...]the entire national immunisation programme was disrupted due to a generalised lack of confidence in all vaccines. Additionally, given the administration of these new vaccines to children, there is an urgent need for thorough surveillance to detect any emerging safety issues in this population and to explore potential genetic and age group variations that could impact a significant cohort of vaccine recipients before they can harm additional vaccine beneficiaries.9 It is necessary, therefore, to leverage the global support and momentum surrounding the malaria vaccine rollout as a catalyst for countries to establish and strengthen their PV systems.10 This presents an opportunity to create solid frameworks for monitoring and managing AEFIs and enhance public health surveillance and response mechanisms. The effective PV systems will play a crucial role in providing timely and accurate data on vaccine safety, especially on the risks associated with the vaccines vis-a-vis the benefits of preventing malaria disease.11 This will bolster public confidence in immunisation programmes and further support the introduction of new vaccines that are becoming increasingly urgently needed to combat emerging and re-emerging infectious diseases. Harmonisation and collaborations provide a proactive solution to promote and protect public health through timely information sharing, strengthening weak management structures, resource mobilisation and processes, and reconstructing fragile and fragmented legal frameworks.14 Lesson from COVID-19 vaccine safety surveillance The post-licensure safety monitoring systems used for COVID-19 vaccines and during the introduction of new therapeutic medicines such as tuberculosis and HIV medicines could serve as a model that can be ameliorated for monitoring the safety of malaria vaccines.

Background: Snakebite envenoming (SBE) is a high-priority, neglected, tropical disease that affects millions of people in developing countries annually. The only available standard drug used for the treatment of SBE is antisnake venom (ASV) which consists of immunoglobulins that have been purified from the plasma of animals hyper-immunized against snake venoms. The use of plants as alternatives for treatment of poisonous bites particularly snakebites is important in remote areas where there might be limited, or no access to hospitals and storage facilities for antivenom. The pharmacological activity of some of the medicinal plants used traditionally in the treatment of SBE have also been scientifically validated. Method: A systematic review will be conducted according to the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies checklist for study quality in animal/in vivo studies. The tool will be modified and validated to assess in vitro models and studies that combine in vivo and in vitro studies. The systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. English published articles on African medicinal plants used in the treatment of snakebite envenoming will be searched in Medline, Embase, and Scopus from 2000 to 2021. Dissemination: The findings of the study will be communicated through publication in peer-reviewed journal and presentation at scientific conferences. Medicinal plants have been important sources for the development of many effective drugs currently available in orthodox medicine. Botanically derived medicines have played a major role in human societies throughout history. Plants components used in traditional medicine gained much attention by many toxinologists as a tool for designing potent antidotes against snake envenoming. Our systematic review will provide a synthesis of the literature on the efficacy of these medicinal plants. We will also appraise the prospects of African medicinal plants with pharmacologically demonstrated activity against snakebite and envenoming.

The Truvada® (tenofovir/emtricitabine) and nevirapine combination is increasingly being prescribed for prevention of mother-to-child HIV transmission. There is presently no documented evidence of teratogenicity of either tenofovir/emtricitabine or nevirapine. We report two cases of spina bifida in infants of mothers on this drug combination.

Despite advances in ACTs, drug-resistant Plasmodium falciparum strains necessitates new therapeutics. While neem’s broad-spectrum bioactivity is well-known, our recent identification of host-plant synergies prompted this focused investigation into neem’s plasmepsin II inhibitors. This study explores Azadirachta indica (neem) phytochemicals as plasmepsin II (Plm-II) inhibitors—a key enzyme in the parasite’s hemoglobin degradation. Using molecular docking (PDB: 1LF3), pharmacophore modeling, induced fit docking (FID), and 100-ns molecular dynamic simulations (MDS), 320 neem compounds were screened, identifying five top candidates: Cerebroside C (highest affinity: -10.665 Kcal/mol, IFD: -14.785 Kcal/mol), Apigenin-7-O-β-D-glucoside, L-Epicatechin, (-)-Epigallocatechin, and Met-pent-carboxylate, all outperforming the standard ligand (-9.573 Kcal/mol). ADMET prediction revealed that while Cerebroside C exhibited the strongest Plm-II interactions (Tyr77/Asp214), it violated Lipinski’s rule and was a P-glycoprotein substrate, limiting bioavailability. In contrast, Apigenin-7-O-β-D-glucoside demonstrated optimal drug-likeness, solubility (-2.69 LogS), and no Pgp efflux. MD simulations further confirmed Apigenin-7-O-β-D-glucoside’s stability, with the Plm-II complex showing low RMSD (≤ 2.6 Å), RMSF (≤ 1.0 Å), 91% hydrogen bond occupancy, and sustained target interactions (Try77/Aps214) via hydrophobic contacts and hydrogen bonds, while radius of gyration (4.5 Å) and SASA analyses affirmed structural integrity. Cerebroside C demonstrates significant plasmepsin II inhibitory potential, while MD simulations establish Apigenin-7-O-β-D-glucoside as a stable Plm-II inhibitor with targeted interactions under dynamic conditions. Notably, the improved drug-likeness and absence of Pgp-mediated efflux of Apigenin-7-O-β-D-glucoside makes it a better pharmaceutically acceptable candidate over Cerebroside C regardless of the latter’s improved binding affinity. Graphical abstract

Antigen uptake and processing by professional antigen-presenting cells (APCs) plays an essential role in the adaptive immune response and subsequent activation of antigen-specific CD4+ and CD8+ T lymphocytes. Consequently, knowledge of antigen interaction with APCs to induce CD8+ and CD4+ T-cell responses is useful in the rational design of peptide-based vaccines. Virus-like particles (VLPs) are non-infectious, self-assembled viral structural proteins that are inherently immunogenic and have been used as scaffolds to display heterologous antigens. Hepatitis B core antigen (HBcAg or HBc) is a widely studied VLP with proven safety and effectiveness as an antigen display platform. Neisseria meningitidis is a Gram-negative bacterium and a causative agent of life-threatening invasive meningococcal disease known to be associated with high morbidity and mortality. There have been effective vaccines for serotypes A, C, W135 and Y produced using their capsular polysaccharides (CPS) but with limited impact against serogroup B (MenB). This study examined the incorporation of meningococcal antigens into HBc. One such antigen fusion HBc-NadA, was used for further studies of binding and uptake into THP-1-derived dendritic cells and macrophages. Comparison was made with native NadA (not coupled to HBc), native HBc and heat denatured NadA. THP-1-derived DCs effectively internalised NadA but failed to internalise HBc or HBc-NadA. THP-1-derived macrophages effectively internalised HBc, HBc-NadA, and NadA. Both HBc and HBc-NadA were internalised through clathrin-mediated endocytosis, macropinocytosis and caveolae-mediated endocytosis. NadA and thermally-denatured NadA (NadA-D) were internalized through clathrin-independent pathways (macropinocytosis and caveolae-mediated endocytosis). HBc-NadA and HBc stimulated M1 macrophage polarization, characteristic of a Th1-skewed response, based on surface marker stimulation (CD80, CD40 and HLA-DR) and IFN-γ, TNF and IL-2 production. NadA alone, by contrast, stimulated M2 macrophage polarisation, characteristic of a Th2-skewed response. The pattern of surface marker stimulation and cytokine production of HBc-NadA was similar to that of HBc. Collectively, these results demonstrate that the uptake and processing of an HBc-fusion displaying a meningococcal antigen (HBc-NadA) is more characteristic of the native VLP (HBc) and distinct from that of the antigen alone (NadA). These findings have generated insights that could assist rational vaccine design using HBc to display bacterial antigens.

Trichuris trichiura is a parasite that infects 500 million people worldwide, leading to colitis, growth retardation and Trichuris dysentery syndrome. There are no licensed vaccines available to prevent Trichuris infection and current treatments are of limited efficacy. Trichuris infections are linked to poverty, reducing children’s educational performance and the economic productivity of adults. We employed a systematic, multi-stage process to identify a candidate vaccine against trichuriasis based on the incorporation of selected T cell epitopes into virus-like particles. We conducted a systematic review to identify the most appropriate in silico prediction tools to predict histocompatibility complex class II (MHC-II) molecule T-cell epitopes. These tools were used to identify candidate MHC-II epitopes from predicted ORFs in the Trichuris genome, selected using inclusion and exclusion criteria. Selected epitopes were incorporated into Hepatitis B core antigen virus-like particles (VLPs). A combined VLP vaccine containing four Trichuris MHC-II T-cell epitopes stimulated dendritic cells and macrophages to produce pro-inflammatory and anti-inflammatory cytokines. The VLPs were internalized and co-localized in the antigen presenting cell lysosomes. Upon challenge infection, mice vaccinated with the VLPs+T-cell epitopes showed a significantly reduced worm burden, and mounted Trichuris-specific IgM and IgG2c antibody responses. The protection of mice by VLPs+T-cell epitopes was characterised by the production of mesenteric lymph node (MLN)-derived Th2 cytokines and goblet cell hyperplasia. Collectively our data establishes that a combination of in silico genome-based CD4+ T cell epitope prediction, combined with VLP delivery, offers a promising pipeline for the development of an effective, safe and affordable helminth vaccine.

Prostate cancer is a leading cause of morbidity and mortality among men globally. In this study, we employed an in silico approach to predict the possible mechanisms of action of selected novel compounds reported against prostate cancer epigenetic targets and their derivatives, exhausting through ADMET profiling, drug-likeness, and molecular docking analyses. The selected compounds: sulforaphane, silibinin, 3, 3’-diindolylmethane (DIM), and genistein largely conformed to ADMET and drug-likeness rules including Lipinski’s. Docking studies revealed strong binding energy of sulforaphane with HDAC6 (− 4.2 kcal/ mol), DIM versus HDAC2 (− 5.2 kcal/mol), genistein versus HDAC6 (− 4.1 kcal/mol), and silibinin against HDAC1 (− 7.0 kcal/mol) coupled with improved binding affinities and biochemical stabilities after derivatization. Findings from this study may provide insight into the potential epigenetic reprogramming mechanisms of these compounds against prostate cancer and could pave the way toward more success in prostate cancer phytotherapy.

The abundant fraction of agricultural waste materials in the environment that poses disposal challenge could be converted into useful value added products such as activated carbon. Palm oil shell based carbon was prepared by two step process using K2CO3 as the chemical activant. The Langmuir surface area, BET surface area and pore volume were 817 m2/g, 707m2/g and 0.31cm3/g. From the FTIR analysis, carbonyls, alkenes and hydroxyls were identified. The SEM image shows gradual formation of pores due to elimination of volatiles and contaminants. Carbonization at 800°C for 2 hours and activation at same temperature for 1h has the highest yield of 23.27%. The proximate and ultimate analysis shows high percentage of carbon and low percentage of ash which is an indication of a good material for production of porous carbon. The activated carbon produced showed basic properties suitable for removal of organic contaminants in aqueous solutions. However, the aim of this study is to produce a green and porous carbon with controlled pores and surface properties for organic contaminants removal from water and wastewater.

There is significantly abundant portion of waste agricultural materials in the world serving as environmental challenge, however, they could be converted into useful value added products like activated carbon. Coconut shell based carbons were synthesized using physical activation by CO2 and chemical activation with potassium hydroxide and potassium acetate. The BET surface areas and pore volumes are 361m2/g and 0.19cm3/g for physical activation, 1353m2/g and 0.61cm3/g for activation with KOH and 622m2/g and 0.31cm3/g for potassium acetate activated carbon. From the Fourier Transform Infrared Spectroscopy analysis, hydroxyls, alkenes and carbonyl functional groups were identified with more prominence on the chemically activated porous carbons. Thermogravimetric analysis (TGA) results showed occurrence of moisture pyrolysis at 105°C, the pyrolysis of hemicellulose and cellulose occurred at 160–390°C and lignin at (390-650°C). Carbonization at 700°C and 2hrs had highest yield of 32%. Physical activation yielded lower surface area with approximately 88% micropores. On the other hand, chemically activation yielded higher surface area with elevated mesopores. The porous carbons can be applied to salvage pollution challenges.