Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model

Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo

Fast preparation of ultrafine monolayered transition-metal dichalcogenide quantum dots using electrochemical shock for explosive detection

A simple, general and fast method called "electrochemical shock" is developed to prepare monolayered transition-metal dichalcogenide (TMD) QDs with an average size of 2-4 nm and an average thickness of 0.85 +/- 0.5 nm with only about 10 min of ultrasonication. Just like nails hammered into a plate, the electrochemical shock with Al3+ ions and the following extraction with the help of oleic acid can disintegrate bulk TMD crystals into ultrafine TMD QDs. The fast-prepared QDs are then applied to detect highly explosive molecules such as 2,4,6-trinitrophenol (TNP) with a low detection limit of 10(-6) M. Our versatile method could be broadly applicable for the fast production of ultrathin QDs of other materials with great promise for various applications

AlGaN-based deep ultraviolet light-emitting diodes grown on nano-patterned sapphire substrates with significant improvement in internal quantum efficiency

We report high-performance AlGaN-based deep ultraviolet light-emitting diodes grown on nano-patterned sapphire substrates (NPSS) using metal - organic chemical vapor deposition. By nanoscale epitaxial lateral overgrowth on NPSS, 4-mu m AIN buffer layer has shown strain relaxation and a coalescence thickness of only 2.5 mu m. The full widths at half-maximum of X-ray diffraction (002) and (102) omega-scan rocking curves of AlN on NPSS are only 694 and 319.1 arcsec. The threading dislocation density in AlGaN-based multi-quantum wells, which are grown on this AIN/NPSS template with a light-emitting wavelength at 283 nm at room temperature, is reduced by 33% compared with that on flat sapphire substrate indicated by atomic force microscopy measurements, and the internal quantum efficiency increases from 30% to 43% revealed by temperature-dependent photoluminescent measurement. (C) 2014 Elsevier B.V. All rights reserved.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000335906000003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701CrystallographyMaterials Science, MultidisciplinaryPhysics, AppliedSCI(E)[email protected]; [email protected]; [email protected]