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https://www.readbyqxmd.com/read/29165651/functional-conservation-of-the-ama1-host-cell-invasion-ligand-between-p-falciparum-and-p-vivax-a-novel-platform-to-accelerate-vaccine-and-drug-development
#1
Damien R Drew, Paul R Sanders, Gretchen Weiss, Paul R Gilson, Brendan S Crabb, James G Beeson
P. vivax and P. falciparum malaria species have diverged significantly in receptor-ligand interactions and host-cell invasion. One protein common to both is the merozoite invasion ligand AMA1. While the general structure of AMA1 is similar between species, their sequences are divergent. Surprisingly, it was possible to genetically replace PfAMA1 with PvAMA1 in P. falciparum parasites. PvAMA1 could complement PfAMA1 function and supported efficient invasion of erythrocytes by P. falciparum. Genetically-modified P...
November 20, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29163936/quality-of-antenatal-care-service-provision-in-health-facilities-across-sub-saharan-africa-evidence-from-nationally-representative-health-facility-assessments
#2
Mufaro Kanyangarara, Melinda K Munos, Neff Walker
Background: Utilization of antenatal care (ANC) services has increased over the past two decades. Continued gains in maternal and newborn health will require an understanding of both access and quality of ANC services. We linked health facility and household survey data to examine the quality of service provision for five ANC interventions across health facilities in sub-Saharan Africa. Methods: Using data from 20 nationally representative health facility assessments - the Service Provision Assessment (SPA) and the Service Availability and Readiness Assessment (SARA), we estimated facility level readiness to deliver five ANC interventions: tetanus toxoid vaccine for pregnant women, intermittent preventive treatment for malaria in pregnancy (IPTp), syphilis detection and treatment in pregnancy, iron supplementation and hypertensive disease case management...
December 2017: Journal of Global Health
https://www.readbyqxmd.com/read/29162636/quantitative-proteomic-profiling-reveals-novel-plasmodium-falciparum-surface-antigens-and-possible-vaccine-candidates
#3
Sandra K Nilsson Bark, Rushdy Ahmad, Kathleen Dantzler, Amanda K Lukens, Mariana De Niz, Matthew J Szucs, Xiaojing Jin, Joanne Cotton, Dietmar Hoffmann, Eva Bric-Furlong, Ray Oomen, Mark Parrington, Dan Milner, Daniel E Neafsey, Steven A Carr, Dyann F Wirth, Matthias Marti
Despite recent efforts towards control and elimination, malaria remains a major public health problem worldwide. Plasmodium falciparum resistance against artemisinin, used in front line combination drugs, is on the rise, and the only approved vaccine shows limited efficacy. Combinations of novel and tailored drug and vaccine interventions are required to maintain the momentum of the current malaria elimination program. Current evidence suggests that strain-transcendent protection against malaria infection can be achieved using whole organism vaccination or with a polyvalent vaccine covering multiple antigens or epitopes...
November 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29162427/disulfide-bond-mapping-of-pfs25-a-recombinant-malaria-transmission-blocking-vaccine-candidate
#4
Shwu-Maan Lee, Jordan Plieskatt, C Richter King
A liquid chromatography tandem-mass spectrometry method was developed to map the eleven disulfide bonds in Pfs25, a malaria transmission-blocking vaccine candidate. The compact and complex nature of Pfs25 has led to difficulties in prior peptide mapping efforts. Here, we report confirmation of proper disulfide pairing of a recombinant Pfs25, by optimizing denaturation and digestion with trypsin/Lys-C. The digested peptides were separated by reversed phase HPLC to obtain the peptide map and elucidate the disulfide linkages...
November 18, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/29162320/controlled-human-infections-a-report-from-the-controlled-human-infection-models-workshop-leiden-university-medical-centre-4-6-may-2016
#5
Meta Roestenberg, Annie Mo, Peter G Kremsner, Maria Yazdanbakhsh
The principle of deliberately infecting humans with infectious agents in a controlled setting, so-called controlled human infections (CHI), is not novel. Many CHI models have a long history and were established decades ago such as the intentional exposure to yellow fever and dengue performed in the 1900's (Reed, 1902) [2]. In these times bioethics and scientific reasoning were in their infancy. Nowadays, clinical trials are highly regulated and CHI are executed worldwide. Controlled human malaria infections and influenza infections are the two most frequently practiced...
November 18, 2017: Vaccine
https://www.readbyqxmd.com/read/29162126/targeting-the-master-regulator-mtor-a-new-approach-to-prevent-the-neurological-of-consequences-of-parasitic-infections
#6
REVIEW
Sheila Donnelly, Wilhelmina M Huston, Michael Johnson, Natalia Tiberti, Bernadette Saunders, Bronwyn O'Brien, Catherine Burke, Maurizio Labbate, Valery Combes
A systematic analysis of 240 causes of death in 2013 revealed that parasitic diseases were responsible for more than one million deaths. The vast majority of these fatalities resulted from protozoan infections presenting with neurological sequelae. In the absence of a vaccine, development of effective therapies is essential to improving global public health. In 2015, an intriguing strategy to prevent cerebral malaria was proposed by Gordon et al. 2015 mBio, 6:e00625. Their study suggested that inhibition of the mammalian target of rapamycin prevented experimental cerebral malaria by blocking the damage to the blood brain barrier and stopping the accumulation of parasitized red blood cells and T cells in the brain...
November 21, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/29155091/dynamic-molecular-events-associated-to-plasmodium-berghei-gametogenesis-through-proteomic-approach
#7
Carlos H S Garcia, Delphine Depoix, Rayner M L Queiroz, Jaques M F Souza, Wagner Fontes, Marcelo V de Sousa, Marlon D M Santos, Paulo C Carvalho, Philippe Grellier, Sébastien Charneau
Plasmodium mature sexual cycle occurs in the vector mosquitoes and ensures the transmission to a new host. Gametogenesis takes place within minutes in the vector midgut. Gametocytes have to complete a deep nuclear reorganization, quick differentiation, and in the case of male gametocytes, intracytoplasmic flagellum assembly that results in free-swimming microgametes required for macrogamete fertilization. In efforts to improve our knowledge of molecular mechanisms involved in gamete morphogenesis, we carried out a nanoLC/MSMS based quantitative proteomic analysis throughout the xanthurenic acid-induced gametogenesis of the rodent parasite P...
November 15, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29153778/the-frontline-of-controlled-human-malaria-infections-a-report-from-the-controlled-human-infection-models-workshop-in-leiden-university-medical-centre-5-may-2016
#8
Meta Roestenberg, Benjamin Mordmüller, Chris Ockenhouse, Annie Mo, Maria Yazdanbakhsh, Peter G Kremsner
Controlled Human Malaria Infection (CHMI) is the most practiced controlled human infection model nowadays and there is an exponential increase in implementation of the model worldwide. During the Controlled Human Infection Models Workshop in Leiden, one day was dedicated to the discussion of the advances made and gaps in Controlled Human Malaria Infection (CHMI) trials. Factors contributing to this impressive expansion in the number of CHMI trials have been related to the ability to perform CHMI using injectable cryopreserved sporozoites (a product from Sanaria Inc...
November 16, 2017: Vaccine
https://www.readbyqxmd.com/read/29146922/molecular-definition-of-multiple-sites-of-antibody-inhibition-of-malaria-transmission-blocking-vaccine-antigen-pfs25
#9
Stephen W Scally, Brandon McLeod, Alexandre Bosch, Kazutoyo Miura, Qi Liang, Sean Carroll, Sini Reponen, Ngan Nguyen, Eldar Giladi, Sebastian Rämisch, Vidadi Yusibov, Allan Bradley, Franck Lemiale, William R Schief, Daniel Emerling, Paul Kellam, C Richter King, Jean-Philippe Julien
The Plasmodium falciparum Pfs25 protein (Pfs25) is a leading malaria transmission-blocking vaccine antigen. Pfs25 vaccination is intended to elicit antibodies that inhibit parasite development when ingested by Anopheles mosquitoes during blood meals. The Pfs25 three-dimensional structure has remained elusive, hampering a molecular understanding of its function and limiting immunogen design. We report six crystal structures of Pfs25 in complex with antibodies elicited by immunization via Pfs25 virus-like particles in human immunoglobulin loci transgenic mice...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29144217/mechanisms-of-naturally-acquired-immunity-to-p-falciparum-and-approaches-to-identify-merozoite-antigen-targets
#10
Julie Healer, Chris Y Chiu, Diana S Hansen
Malaria is one the most serious infectious diseases with over 200 million clinical cases annually. Most cases of the severe disease are caused by Plasmodium falciparum. The blood stage of Plasmodium parasite is entirely responsible for malaria-associated pathology. The population most susceptible to severe malaria are children under the age of 5, with low levels of immunity. It is only after many years of repeated exposure that individuals living in endemic areas develop clinical immunity. This form of protection prevents clinical episodes by substantially reducing parasite burden...
November 16, 2017: Parasitology
https://www.readbyqxmd.com/read/29141757/protein-specific-features-associated-with-variability-in-human-antibody-responses-to-plasmodium-falciparum-malaria-antigens
#11
Eugene W Liu, Jeff Skinner, Tuan M Tran, Krishan Kumar, David L Narum, Aarti Jain, Aissata Ongoiba, Boubacar Traore, Philip L Felgner, Peter D Crompton
The magnitude of antibody responses varies across the individual proteins that constitute any given microorganism, both in the context of natural infection and vaccination with attenuated or inactivated pathogens. The protein-specific factors underlying this variability are poorly understood. In 267 individuals exposed to intense seasonal malaria, we examined the relationship between immunoglobulin G (IgG) responses to 861 Plasmodium falciparum proteins and specific features of these proteins, including their subcellular location, relative abundance, degree of polymorphism, and whether they are predicted to have human orthologs...
October 23, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29141739/advancing-global-health-through-development-and-clinical-trials-partnerships-a-randomized-placebo-controlled-double-blind-assessment-of-safety-tolerability-and-immunogenicity-of-plasmodium-falciparum-sporozoites-vaccine-for-malaria-in-healthy-equatoguinean
#12
Ally Olotu, Vicente Urbano, Ali Hamad, Martin Eka, Mwajuma Chemba, Elizabeth Nyakarungu, Jose Raso, Esther Eburi, Dolores O Mandumbi, Dianna Hergott, Carl D Maas, Mitoha O Ayekaba, Diosdado N Milang, Matilde R Rivas, Tobias Schindler, Oscar M Embon, Adam J Ruben, Elizabeth Saverino, Yonas Abebe, Natasha Kc, Eric R James, Tooba Murshedkar, Anita Manoj, Sumana Chakravarty, Minglin Li, Matthew Adams, Chris Schwabe, Luis Segura, Claudia Daubenberger, Marcel Tanner, Thomas L Richie, Peter F Billingsley, B Kim Lee Sim, Salim Abdulla, Stephen L Hoffman
Equatorial Guinea (EG) has implemented a successful malaria control program on Bioko Island. A highly effective vaccine would be an ideal complement to this effort and could lead to halting transmission and eliminating malaria. Sanaria(®)Plasmodium falciparum sporozoites (PfSPZ) Vaccine is being developed for this purpose. To begin the process of establishing the efficacy of and implementing a PfSPZ Vaccine mass vaccination program in EG, we decided to conduct a series of clinical trials of PfSPZ Vaccine on Bioko Island...
October 30, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29138641/naturally-acquired-antibody-responses-to-a-synthetic-malaria-antigen-as202-11
#13
Rebeka Nazareth, Pius Horumpende, Tolbert Sonda, Arnold Ndaro, Edson Mollel, Eliakim Paul, Emmanuel Athanase, Jaffu Chilongola
Background: A major challenge to malaria vaccine development is identification of protective epitopes and respective protective immune responses. Objective: To characterize naturally acquired Immunoglobulin G (IgG) responses to the synthetic peptide AS202.11, a malaria vaccine candidate. Methodology: This community based cross-sectional study enrolled 320 participants aged 1 year and above. Demographic information was recorded through interviews...
2017: Journal of Tropical Medicine
https://www.readbyqxmd.com/read/29138320/structural-basis-for-antibody-recognition-of-the-nanp-repeats-in-plasmodium-falciparum-circumsporozoite-protein
#14
David Oyen, Jonathan L Torres, Ulrike Wille-Reece, Christian F Ockenhouse, Daniel Emerling, Jacob Glanville, Wayne Volkmuth, Yevel Flores-Garcia, Fidel Zavala, Andrew B Ward, C Richter King, Ian A Wilson
Acquired resistance against antimalarial drugs has further increased the need for an effective malaria vaccine. The current leading candidate, RTS,S, is a recombinant circumsporozoite protein (CSP)-based vaccine against Plasmodium falciparum that contains 19 NANP repeats followed by a thrombospondin repeat domain. Although RTS,S has undergone extensive clinical testing and has progressed through phase III clinical trials, continued efforts are underway to enhance its efficacy and duration of protection. Here, we determined that two monoclonal antibodies (mAbs 311 and 317), isolated from a recent controlled human malaria infection trial exploring a delayed fractional dose, inhibit parasite development in vivo by at least 97%...
November 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29136653/drlumi-an-open-source-package-to-manage-data-calibrate-and-conduct-quality-control-of-multiplex-bead-based-immunoassays-data-analysis
#15
Hector Sanz, John J Aponte, Jaroslaw Harezlak, Yan Dong, Aintzane Ayestaran, Augusto Nhabomba, Maxmillian Mpina, Obiang Régis Maurin, Núria Díez-Padrisa, Ruth Aguilar, Gemma Moncunill, Agnandij Selidji Todagbe, Claudia Daubenberger, Carlota Dobaño, Clarissa Valim
Multiplex bead-based immunoassays are used to measure concentrations of several analytes simultaneously. These assays include control standard curves (SC) to reduce between-plate variability and normalize quantitation of analytes of biological samples. Suboptimal calibration might result in large random error and decreased number of samples with analyte concentrations within the limits of quantification. Suboptimal calibration may be a consequence of poor fitness of the functions used for the SC, the treatment of the background noise and the method used to estimate the limits of quantification...
2017: PloS One
https://www.readbyqxmd.com/read/29132995/comparative-functional-potency-of-dna-vaccines-encoding-plasmodium-falciparum-transmission-blocking-target-antigens-pfs48-45-and-pfs25-administered-alone-or-in-combination-by-in-vivo-electroporation-in-rhesus-macaques
#16
Dibyadyuti Datta, Geetha P Bansal, Brooke Grasperge, Dale S Martin, Mario Philipp, Dietlind Gerloff, Barry Ellefsen, Drew Hannaman, Nirbhay Kumar
Antibodies recognizing conformational epitopes in Pfs48/45, an antigen expressed on the surface of Plasmodium falciparum gametes and zygotes, have firmly established Pfs48/45 as a promising transmission blocking vaccine (TBV) candidate. However, it has been difficult to reproducibly express Pfs48/45 in a variety of recombinant expression systems. The goal of our studies was to evaluate functional immunogenicity of Pfs48/45 using DNA vaccine format in rhesus macaques. An additional goal was to ensure that when used in combination with another malarial antigen, specific immunity to both antigens was not compromised...
November 10, 2017: Vaccine
https://www.readbyqxmd.com/read/29132428/characterization-of-pb51-in-plasmodium-berghei-as-a-malaria-vaccine-candidate-targeting-both-asexual-erythrocytic-proliferation-and-transmission
#17
Jian Wang, Wenqi Zheng, Fei Liu, Yaru Wang, Yiwen He, Li Zheng, Qi Fan, Enjie Luo, Yaming Cao, Liwang Cui
BACKGROUND: A vaccine that targets multiple developmental stages of malaria parasites would be an effective tool for malaria control and elimination. METHODS: A conserved gene in Plasmodium, the Plasmodium berghei gene (PBANKA_020570) encoding a 51 kDa protein (pb51 gene), was identified through search of the PlasmoDB database using a combination of expression and protein localization criteria. A partial domain of the Pb51 protein was expressed in a prokaryotic expression system (rPb51) and used for immunization in mice...
November 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29128848/antimalarial-activity-of-malaria-box-compounds-against-plasmodium-falciparum-clinical-isolates
#18
Jersley D Chirawurah, Felix Ansah, Prince B Nyarko, Samuel Duodu, Yaw Aniweh, Gordon A Awandare
Malaria remains a major cause of childhood deaths in resource-limited settings. In the absence of an effective vaccine, drugs and other interventions have played very significant roles in combating the scourge of malaria. The recent reports of resistance to artemisinin necessitate the need for new antimalarial drugs with novel mechanisms of action. Towards the development of new, affordable and easily accessible antimalarial drugs for endemic regions, the Medicines for Malaria Venture (MMV) assembled a total of 400 active antimalarial compounds called the Malaria Box...
October 16, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29128519/genetic-structure-of-two-erythrocyte-binding-antigens-of-plasmodium-falciparum-reveals-a-contrasting-pattern-of-selection
#19
Pramita Chowdhury, Srikanta Sen, Sumana Datta Kanjilal, Sanghamitra Sengupta
Erythrocyte binding antigens 175 (EBA-175) and 140 (EBA-140) play key roles in erythrocyte invasion by binding to glycophorin A (GPA) and C (GPC) respectively in human malaria. Since antigenic variation in malaria endemic region is a major barrier to development of effective vaccine, we explore the nature and pattern of sequence diversity of these two vaccine candidates in Kolkata, India. Population genetic parameters based on parasite sequences representing region II of Pfeba-175 and Pfeba-140 genes were estimated using DnaSP V...
November 8, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29123481/development-in-assay-methods-for-in-vitro-antimalarial-drug-efficacy-testing-a-systematic-review
#20
REVIEW
Shweta Sinha, Phulen Sarma, Rakesh Sehgal, Bikash Medhi
The emergence and spread of drug resistance are the major challenges in malaria eradication mission. Besides various strategies laid down by World Health Organization, such as vector management, source reduction, early case detection, prompt treatment, and development of new diagnostics and vaccines, nevertheless the need for new and efficacious drugs against malaria has become a critical priority on the global malaria research agenda. At several screening stages, millions of compounds are screened (1,000-2,000,000 compounds per screening campaign), before pre-clinical trials to select optimum lead...
2017: Frontiers in Pharmacology
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