Publications by authors named "Charlotte Weller"

Tools to evaluate and accelerate tuberculosis (TB) vaccine development are needed to advance global TB control strategies. Validated human infection studies for TB have the potential to facilitate breakthroughs in understanding disease pathogenesis, identify correlates of protection, develop diagnostic tools, and accelerate and de-risk vaccine and drug development. However, key challenges remain for realizing the clinical utility of these models, which require further discussion and alignment among key stakeholders.

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For vaccine development and adoption decisions, the 'Full Value of Vaccine Assessment' (FVVA) framework has been proposed by the WHO to expand the range of evidence available to support the prioritization of candidate vaccines for investment and eventual uptake by low- and middle-income countries. Recent applications of the FVVA framework have already shown benefits. Building on the success of these applications, we see important new opportunities to maximize the future utility of FVVAs to country and global stakeholders and provide a proof-of-concept for analyses in other areas of disease control and prevention.

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Article Synopsis
  • Broadly protective coronavirus vaccines are essential for fighting off future versions of SARS-CoV-2 and other novel coronaviruses, helping to reduce the impact of potential outbreaks.
  • The Coronavirus Vaccines Research and Development (R&D) Roadmap (CVR) is a structured plan funded by major foundations, created through collaboration among experts, and outlines vital research areas and strategic goals.
  • Organized into five key topics, the CVR includes 20 goals and 86 R&D milestones, with 26 identified as high priority, to help direct funding and research efforts in making effective vaccines.
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Human infection (or challenge) studies involve the intentional administration of a pathogen (challenge agent) to volunteers. The selection, isolation, development and production of the challenge agent is one of the first steps in developing a challenge study and critical for minimising the risk to volunteers. Regulatory oversight for this production differs globally.

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Improved influenza vaccines are urgently needed to reduce the burden of seasonal influenza and to ensure a rapid and effective public-health response to future influenza pandemics. The Influenza Vaccines Research and Development (R&D) Roadmap (IVR) was created, through an extensive international stakeholder engagement process, to promote influenza vaccine R&D. The roadmap covers a 10-year timeframe and is organized into six sections: virology; immunology; vaccinology for seasonal influenza vaccines; vaccinology for universal influenza vaccines; animal and human influenza virus infection models; and policy, finance, and regulation.

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For Duchenne muscular dystrophy (DMD), a common myopathy that leads to severe disability, no causal therapy is available. Glucocorticosteroids improve patients' muscle strength, but their long-term use is limited by negative side effects. Thus, pharmacological modifications of glucocorticosteroids are required to increase the efficacy by drug targeting.

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Mast cells are tissue-resident cells best known for their role in allergy and host defence against helminth parasites. They are involved in responses against other pathogenic infections, wound healing and inflammatory disease. Committed mast cell progenitors are released from the bone marrow into the circulation, from where they are recruited into tissues to complete their maturation under the control of locally produced cytokines and growth factors.

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Although MCs (mast cells) were discovered over 100 years ago, for the majority of this time their function was linked almost exclusively to allergy and allergic disease with few other roles in health and disease. The engineering of MC-deficient mice and engraftment of these mice with MCs deficient in receptors or mediators has advanced our knowledge of the role of MCs in vivo. It is now known that MCs have very broad and varied roles in both physiology and disease which will be reviewed here with a focus on some of the most recent discoveries over the last year.

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Tissue-resident mast cells (MCs) are important in allergic diseases. In a mouse model of allergic airways inflammation, an increase in peribronchiolar MCs was associated with increased concentrations of the chemokine CCL2 in lung lavage. MC progenitors (MCps) arising in bone marrow (BM) are recruited to tissues by transendothelial migration, and we found that CCL2 is chemotactic for MCps in freshly isolated BM in vitro.

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The mechanisms governing the population of tissues by mast cells are not fully understood, but several studies using human mast cells have suggested that expression of the chemokine receptor CCR3 and migration to its ligands may be important. In CCR3-deficient mice, a change in mast cell tissue distribution in the airways following allergen challenge was reported compared with wild-type mice. In addition, there is evidence that CCR3 is important in mast cell maturation in mouse.

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Liposomal encapsulation leads to enhanced efficacy of glucocorticosteroids (GS) in treatment of autoimmune diseases. Here we compare liposomal prednisolone (PL) to liposomal methylprednisolone (MPL) in chronic-relapsing myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE), a model closely reflecting aspects of multiple sclerosis (MS). At the maximum of the first relapse, a single dose of PL or MPL was applied at 10 mg/kg or at 4 mg/kg and compared to classical methylprednisolone (MP) pulse therapy.

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Mast cells are long-lived cells that are principally recognized for their effector function in helminth infections and allergic reactions. These cells are derived from pluripotential hematopoietic stem cells in the bone marrow that give rise to committed mast cell progenitors in the blood and are recruited to tissues, where they mature. Little is known about the chemotactic signals responsible for recruitment of progenitors and localization of mature mast cells.

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Background: Little is known about the mechanisms that regulate the selective recruitment of basophils to sites of allergic inflammation.

Objective: Here we examine the role of stem cell factor (SCF) in the regulation of basophil function.

Methods: Human basophils were isolated from peripheral blood, and their migration was investigated in chemotaxis assays.

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Mast cells are tissue-resident cells with important functions in allergy and inflammation. Pluripotential hematopoietic stem cells in the bone marrow give rise to committed mast cell progenitors that transit via the blood to tissues throughout the body, where they mature. Knowledge is limited about the factors that release mast cell progenitors from the bone marrow or recruit them to remote tissues.

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