Therapeutics and Prevention
Editor's Pick Research Article | Therapeutics and PreventionDectin-1-Targeted Antifungal Liposomes Exhibit Enhanced EfficacyThe fungus Aspergillus fumigatus causes pulmonary invasive aspergillosis resulting in nearly 100,000 deaths each year. Patients are often treated with antifungal drugs such as amphotericin B (AmB) loaded into liposomes (AmB-LLs), but all antifungal drugs, including AmB-LLs, have serious limitations due to human toxicity and insufficient fungal cell killing. Even with...
Research Article | Therapeutics and PreventionAnticytomegalovirus Peptides Point to New Insights for CMV Entry Mechanisms and the Limitations of In Vitro ScreeningsIn the absence of an effective vaccine to prevent HCMV infections, alternative interventions must be developed. Prevention of viral entry into susceptible cells is an attractive alternative strategy. Here we report that heparan sulfate-binding peptides effectively inhibit entry into fibroblasts of in vitro-derived CMVs and partially inhibit in vivo-derived CMVs. This includes the inhibition of urine-derived HCMV (uCMV...
Research Article | Therapeutics and PreventionDose-Dependent Differences in HIV Inhibition by Different Interferon Alpha Subtypes While Having Overall Similar Biologic EffectsElucidating the functional role of the IFN-α subtypes is of particular importance for the development of efficacious therapies using exogenous IFN-α. Specifically, this will help define whether IFN therapy should be based on the use of pathogen-dependent IFN subtypes or, rather, IFN mutants with optimized IFNAR binding properties.
Research Article | Therapeutics and PreventionA Translational Pharmacokinetic Rat Model of Cerebral Spinal Fluid and Plasma Concentrations of CefepimeThis study defines the transit of cefepime between plasma and cerebral spinal fluid (CSF) in a rat model. Male Sprague-Dawley rats received cefepime intravenously. Plasma samples were obtained via a second dedicated intravenous catheter. CSF sampling occurred via an intracisternal catheter. Drug exposures and transfer from the plasma to the CSF during the first 24 h were calculated. The median CSF/blood percentage of penetration was 19...
Research Article | Therapeutics and PreventionRepurposing Pilocarpine Hydrochloride for Treatment of Candida albicans InfectionsCandida albicans is the most common human fungal pathogen with an estimated crude mortality rate of 40%. The ability of the organism to switch from the yeast to hyphal form and produce biofilms are important virulence factors. C. albicans infections are combatted by the host immune system. However...
Opinion/Hypothesis | Therapeutics and PreventionCD8+ Cytotoxic-T-Lymphocyte Breadth Could Facilitate Early Immune Detection of Immunodeficiency Virus-Derived Epitopes with Limited Expression LevelsCytotoxic-T-lymphocyte (CTL) responses are important to control the replication of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Accumulating evidence suggests that the ability of a few immunodominant T-cell populations to detect and kill HIV/SIV-infected cells is important in individuals with a protective major histocompatibility complex class I (MHC-I) allele.
Commentary | Therapeutics and PreventionAntibodies Are Major Drivers of Protection against Lethal Aerosol Infection with Highly Pathogenic Burkholderia spp.Burkholderia pseudomallei and Burkholderia mallei are the causative agents of melioidosis and glanders, respectively. There is no vaccine to protect against these highly pathogenic bacteria, and there is concern regarding their emergence as global public health (...
Research Article | Therapeutics and PreventionBurkholderia pseudomallei ΔtonB Δhcp1 Live Attenuated Vaccine Strain Elicits Full Protective Immunity against Aerosolized Melioidosis InfectionIn recent years, an increasing number of melioidosis cases have been reported in several regions where melioidosis is endemic and in areas where melioidosis had not commonly been diagnosed. Currently, the estimated burden of disease is around 165,000 new cases annually, including 89,000 cases that have fatal outcomes. This life-threatening infectious disease is caused by B....
Observation | Therapeutics and PreventionA Novel, Rapid, and Low-Volume Assay for Therapeutic Drug Monitoring of Posaconazole and Other Long-Chain Azole-Class Antifungal DrugsThis work describes an effective assay for TDM of long-chain azole-class antifungal drugs that can be used in diluted human serum samples. This assay will provide a quick, cost-effective method for monitoring concentrations of drugs such as posaconazole that exhibit well-documented pharmacokinetic variability. Our rGO-aptamer assay has the potential to improve health care for those struggling to treat fungal infections in rural or...
Research Article | Therapeutics and PreventionDevelopment of an Opsonophagocytic Killing Assay Using HL-60 Cells for Detection of Functional Antibodies against Streptococcus pyogenesMeasuring functional opsonic antibodies against group A streptococci is an important component of the clinical development path for effective vaccines. Prior studies have used an assay developed over 60 years ago that relied on whole human blood as the source of phagocytes and complement, both of which are critical components of antibody-mediated killing assays. In this study, we adapted an assay that uses the HL-60 human promyelocytic...