Identification of two new protective pre-erythrocytic malaria vaccine antigen candidates

<p>Abstract</p> <p>Background</p> <p>Despite years of effort, a licensed malaria vaccine is not yet available. One of the obstacles facing the development of a malaria vaccine is the extensive heterogeneity of many of the current malaria vaccine antigens. To counteract this antigenic diversity, an effective malaria vaccine may need to elicit an immune response against multiple malaria antigens, thereby limiting the negative impact of variability in any one antigen. Since most of the malaria vaccine antigens that have been evaluated in people have not elicited a protective immune response, there is a need to identify additional protective antigens. In this study, the efficacy of three pre-erythrocytic stage malaria antigens was evaluated in a <it>Plasmodium yoelii</it>/mouse protection model.</p> <p>Methods</p> <p>Mice were immunized with plasmid DNA and vaccinia virus vectors that expressed one, two or all three <it>P. yoelii </it>vaccine antigens. The immunized mice were challenged with 300 <it>P. yoelii </it>sporozoites and evaluated for subsequent infection.</p> <p>Results</p> <p>Vaccines that expressed any one of the three antigens did not protect a high percentage of mice against a <it>P. yoelii </it>challenge. However, vaccines that expressed all three antigens protected a higher percentage of mice than a vaccine that expressed PyCSP, the most efficacious malaria vaccine antigen. Dissection of the multi-antigen vaccine indicated that protection was primarily associated with two of the three <it>P. yoelii </it>antigens. The protection elicited by a vaccine expressing these two antigens exceeded the sum of the protection elicited by the single antigen vaccines, suggesting a potential synergistic interaction.</p> <p>Conclusions</p> <p>This work identifies two promising malaria vaccine antigen candidates and suggests that a multi-antigen vaccine may be more efficacious than a single antigen vaccine.</p

A Lithium-ion Battery Using Partially Lithiated Graphite Anode and Amphi-redox LiMn2O4 Cathode

Delithiation followed by lithiation of Li+-occupied (n-type) tetrahedral sites of cubic LiMn2O4 spine! (LMO) at similar to 4V(Li/Li+). (delivering-100 mAhg(LMO)-1) has been used for energy storage by lithium ion batteries (LIBs). In this work, we utilized unoccupied (p-type) octahedral sites of LMO available for lithiation at -3V(Li/Li). (delivering additional -100 mAh gLmo(-1)) that have never been used for LI Bs in full cell configuration. The whole capacity of amphi-redox LMO, including both oxidizable n-type and reducible p-type redox sites, at -200 mAh g(LMO)-1 was realized by using the reactions both at 4 VLi/Li+ and 3 VLi/Li+. Durable reversibility of the 3 V reaction was achieved by graphene-wrapping LMO nanoparticles (LMO@Gn). Prelithiated graphite (LinC6,, n &lt; 1) was used as anodes to lithiate the unoccupied octahedral sites of LMO for the 3V reactio

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