Safety, Immunogenicity, and Protective Efficacy of Intradermal Immunization with Aseptic, Purified, Cryopreserved Plasmodium falciparum Sporozoites in Volunteers Under Chloroquine Prophylaxis

Immunization of volunteers under chloroquine prophylaxis by bites of *Plasmodium falciparum* sporozoite (PfSPZ)–infected mosquitoes induces > 90% protection against controlled human malaria infection (CHMI). We studied intradermal immunization with cryopreserved, infectious PfSPZ in volunteers taking chloroquine (PfSPZ chemoprophylaxis vaccine [CVac]). Vaccine groups 1 and 3 received 3x monthly immunizations with 7.5 x 10^4 PfSPZ. Control groups 2 and 4 received normal saline. Groups 1 and 2 underwent CHMI (#1) by mosquito bite 60 days after the third immunization. Groups 3 and 4 were boosted 168 days after the third immunization and underwent CHMI (#2) 137 days later. Vaccinees (11/20, 55%) and controls (6/10, 60%) had the same percentage of mild to moderate solicited adverse events. After CHMI #1, 8/10 vaccinees (group 1) and 5/5 controls (group 2) became parasitemic by microscopy; the two negatives were positive by quantitative real-time polymerase chain reaction (qPCR). After CHMI #2, all vaccinees in group 3 and controls in group 4 were parasitemic by qPCR. Vaccinees showed weak antibody and no detectable cellular immune responses. Intradermal immunization with up to 3 x 10^5 PfSPZ-CVac was safe, but induced only minimal immune responses and no sterile protection against Pf CHMI. INTRODUCTIO

A randomized feasibility trial comparing four antimalarial drug regimens to induce Plasmodium falciparum gametocytemia in the controlled human malaria infection model

Background: Malaria elimination strategies require a thorough understanding of parasite transmission from human to mosquito. A clinical model to induce gametocytes to understand their dynamics and evaluate transmission-blocking interventions (TBI) is currently unavailable. Here, we explore the use of the well-established Controlled Human Malaria Infection model (CHMI) to induce gametocyte carriage with different antimalarial drug regimens. Methods: In a single centre, open-label randomised tr

Energy loss due to defect formation from 206Pb recoils in SuperCDMS germanium detectors

The Super Cryogenic Dark Matter Search experiment at the Soudan Underground Laboratory studied energy loss associated with defect formation in germanium crystals at mK temperatures using in situ 210Pb sources. We examine the spectrum of 206Pb nuclear recoils near its expected 103 keV endpoint energy and determine an energy loss of (6:08 ± 0:18)%, which we attribute to defect formation. From this result and using TRIM simulations, we extract the first experimentally determined average displacement threshold energy of 19.7+0.6−0.5 eV for germanium. This has implications for the analysis thresholds of future germanium-based dark matter searches

Staining Myelin And Myelin-like Degradation Products In The Spinal Cords Of Chronic Experimental Allergic Encephalomyelitis (cr-eae) Rats Using Sudan Black B Staining Of Glycol Methacrylate-embedded Material.

A high-resolution light-microscopical (HRLM) technique is described to visualize myelin, and macrophages containing degradation products of myelin, in the spinal cords of chronic relapsing experimental allergic encephalomyelitis (Cr-EAE) rats. This HRLM technique was developed to optimalize the correlation between nuclear magnetic resonance (NMR) characteristics and histopathological images in this well-established animal model for multiple sclerosis (MS). Spinal cords were fixed by perfusion with a combination of cacodylate-buffered glutaraldehyde and formaldehyde, post-fixed in Dalton's fixative (containing osmium tetroxide), rinsed in water, processed in ethanol, acetone, and embedded in glycol methacrylate resin (Technovit 7100/HistoResin). Semi-thin sections were stained with Sudan Black B and counterstained with Cresyl Fast Violet, resulting in black staining of myelin and its degradation products, with blue/violet staining of demyelinated axons and other tissue elements. These dyes were selected with the aid of a numerical model of staining, which took both access and lipophilicity into account. The staining procedure is simple and highly reproducible. The resulting images are contrast rich, and combine excellent morphology with a high degree of lipid retention