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Malaria vaccine

Anthony L Cunningham, Nathalie Garçon, Oberdan Leo, Leonard R Friedland, Richard Strugnell, Béatrice Laupèze, Mark Doherty, Peter Stern
In the 21st century, an array of microbiological and molecular allow antigens for new vaccines to be specifically identified, designed, produced and delivered with the aim of optimising the induction of a protective immune response against a well-defined immunogen. New knowledge about the functioning of the immune system and host pathogen interactions has stimulated the rational design of vaccines. The design toolbox includes vaccines made from whole pathogens, protein subunits, polysaccharides, pathogen-like particles, use of viral/bacterial vectors, plus adjuvants and conjugation technology to increase and broaden the immune response...
October 18, 2016: Vaccine
Sittiporn Pattaradilokrat, Vorthon Sawaswong, Phumin Simpalipan, Morakot Kaewthamasorn, Napaporn Siripoon, Pongchai Harnyuttanakorn
BACKGROUND: An effective malaria vaccine is an urgently needed tool to fight against human malaria, the most deadly parasitic disease of humans. One promising candidate is the merozoite surface protein-3 (MSP-3) of Plasmodium falciparum. This antigenic protein, encoded by the merozoite surface protein (msp-3) gene, is polymorphic and classified according to size into the two allelic types of K1 and 3D7. A recent study revealed that both the K1 and 3D7 alleles co-circulated within P. falciparum populations in Thailand, but the extent of the sequence diversity and variation within each allelic type remains largely unknown...
October 21, 2016: Malaria Journal
Alan F Cowman, Julie Healer, Danushka Marapana, Kevin Marsh
Malaria has been a major global health problem of humans through history and is a leading cause of death and disease across many tropical and subtropical countries. Over the last fifteen years renewed efforts at control have reduced the prevalence of malaria by over half, raising the prospect that elimination and perhaps eradication may be a long-term possibility. Achievement of this goal requires the development of new tools including novel antimalarial drugs and more efficacious vaccines as well as an increased understanding of the disease and biology of the parasite...
October 20, 2016: Cell
C Speake, A Pichugin, T Sahu, V Malkov, R Morrison, Y Pei, L Juompan, N Milman, S Zarling, C Anderson, N J MacDonald, S Wong-Madden, J Wendler, A Ishizuka, Z W MacMillen, V Garcia, S H Kappe, U Krzych, P E Duffy
[This corrects the article DOI: 10.1371/journal.pone.0159449.].
2016: PloS One
G MuŽíková, R Laga
Vaccines have helped considerably in eliminating some life-threatening infectious diseases in past two hundred years. Recently, human medicine has focused on vaccination against some of the world's most common infectious diseases (AIDS, malaria, tuberculosis, etc.), and vaccination is also gaining popularity in the treatment of cancer or autoimmune diseases. The major limitation of current vaccines lies in their poor ability to generate a sufficient level of protective antibodies and T cell responses against diseases such as HIV, malaria, tuberculosis and cancers...
October 20, 2016: Physiological Research
Kawsar R Talaat, Ruth D Ellis, Janet Hurd, Autumn Hentrich, Erin Gabriel, Noreen A Hynes, Kelly M Rausch, Daming Zhu, Olga Muratova, Raul Herrera, Charles Anderson, David Jones, Joan Aebig, Sarah Brockley, Nicholas J MacDonald, Xiaowei Wang, Michael P Fay, Sara A Healy, Anna P Durbin, David L Narum, Yimin Wu, Patrick E Duffy
Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. Pfs25 is a leading TBV candidate, and previous studies conducted in animals demonstrated an improvement of its functional immunogenicity after conjugation to EPA, a recombinant, detoxified ExoProtein A from Pseudomonas aeruginosa. In this report, we describe results of an open-label, dose-escalating Phase 1 trial to assess the safety and immunogenicity of Pfs25-EPA conjugates formulated with Alhydrogel®...
2016: PloS One
Neha Chaturvedi, Praveen K Bharti, Archana Tiwari, Neeru Singh
Transmission blocking malaria vaccines are aimed to block the development and maturity of sexual stages of parasite within mosquitoes. The vaccine candidate antigens (Pfs25, Pfs48/45, Pfs230) that have shown transmission blocking immunity in model systems are in different stages of development. These antigens are immunogenic with limited genetic diversity. Pfs25 is a leading candidate and currently in phase I clinical trial. Efforts are now focused on the cost-effective production of potent antigens using safe adjuvants and optimization of vaccine delivery system that are capable of inducing strong immune responses...
June 2016: Indian Journal of Medical Research
Emma R Cold, Gerardo R Vasta, Josà A Fernà Ndez-Robledo
Perkinsus marinus is a protozoan parasite of molluscs that can be propagated in vitro in a defined culture medium, in the absence of host cells. We previously reported that P. marinus trophozoites can be transfected with high efficiency by electroporation using a plasmid based on MOE, a highly expressed gene, and proposed its potential use as a "pseudoparasite". This is a novel gene expression platform for parasites of medical relevance for which the choice of the surrogate organism is based on phylogenetic affinity to the parasite of interest, while taking advantage of the whole engineered surrogate organism as a vaccination adjuvant...
October 10, 2016: Journal of Parasitology
Yasser El-Manzalawy, Elyse E Munoz, Scott E Lindner, Vasant Honavar
Accurate and comprehensive identification of surface exposed proteins (SEPs) in parasites is a key step in developing novel subunit vaccines. However, the reliability of mass spectrometry-based high-throughput methods for proteome-wide mapping of SEPs continues to be limited due to high rates of false positives (i.e., proteins mistakenly identified as surface exposed) as well as false negatives (i.e., SEPs not detected due to low expression or other technical limitations). We propose a framework called PlasmoSEP for the reliable identification of SEPs using a novel semi-supervised learning algorithm that combines SEPs identified by high-throughput experiments and expert annotation of high-throughput data to augment labeled data for training a predictive model...
October 7, 2016: Proteomics
Pilar Requena, Edmilson Rui, Norma Padilla, Flor E Martínez-Espinosa, Maria Eugenia Castellanos, Camila Bôtto-Menezes, Adriana Malheiro, Myriam Arévalo-Herrera, Swati Kochar, Sanjay K Kochar, Dhanpat K Kochar, Alexandra J Umbers, Maria Ome-Kaius, Regina Wangnapi, Dhiraj Hans, Michela Menegon, Francesca Mateo, Sergi Sanz, Meghna Desai, Alfredo Mayor, Chetan C Chitnis, Azucena Bardají, Ivo Mueller, Stephen Rogerson, Carlo Severini, Carmen Fernández-Becerra, Clara Menéndez, Hernando Del Portillo, Carlota Dobaño
P. vivax infection during pregnancy has been associated with poor outcomes such as anemia, low birth weight and congenital malaria, thus representing an important global health problem. However, no vaccine is currently available for its prevention. Vir genes were the first putative virulent factors associated with P. vivax infections, yet very few studies have examined their potential role as targets of immunity. We investigated the immunogenic properties of five VIR proteins and two long synthetic peptides containing conserved VIR sequences (PvLP1 and PvLP2) in the context of the PregVax cohort study including women from five malaria endemic countries: Brazil, Colombia, Guatemala, India and Papua New Guinea (PNG) at different timepoints during and after pregnancy...
October 2016: PLoS Neglected Tropical Diseases
Saw Thu Wah, Hathairad Hananantachai, Usanee Kerdpin, Chotiros Plabplueng, Virapong Prachayasittikul, Pornlada Nuchnoi
Cerebral malaria is still a deleterious health problem in tropical countries. The wide spread of malarial drug resistance and the lack of an effective vaccine are obstacles for disease management and prevention. Parasite and human genetic factors play important roles in malaria susceptibility and disease severity. The malaria parasite exerted a potent selective signature on the human genome, which is apparent in the genetic polymorphism landscape of genes related to pathogenesis. Currently, much genomic data and a novel body of knowledge, including the identification of microRNAs, are being increasingly accumulated for the development of laboratory testing cassettes for cerebral malaria prevention...
2016: Tropical Medicine and Health
(no author information available yet)
For the first time a malaria vaccine is to be tested for possible inclusion in national immunization programmes. Malcolm Molyneux tells Fiona Fleck why governments may need to work hard to convince people of its benefits.
September 1, 2016: Bulletin of the World Health Organization
Jairo Andres Fonseca, Monica Cabrera-Mora, Balwan Singh, Joseli Oliveira-Ferreira, Josué da Costa Lima-Junior, J Mauricio Calvo-Calle, Jose Manuel Lozano, Alberto Moreno
The most widespread Plasmodium species, Plasmodium vivax, poses a significant public health threat. An effective vaccine is needed to reduce global malaria burden. Of the erythrocytic stage vaccine candidates, the 19 kDa fragment of the P. vivax Merozoite Surface Protein 1 (PvMSP119) is one of the most promising. Our group has previously defined several promiscuous T helper epitopes within the PvMSP1 protein, with features that allow them to bind multiple MHC class II alleles. We describe here a P. vivax recombinant modular chimera based on MSP1 (PvRMC-MSP1) that includes defined T cell epitopes genetically fused to PvMSP119...
October 6, 2016: Scientific Reports
Giovanni Benelli, Claire L Jeffries, Thomas Walker
Mosquitoes represent the major arthropod vectors of human disease worldwide transmitting malaria, lymphatic filariasis, and arboviruses such as dengue virus and Zika virus. Unfortunately, no treatment (in the form of vaccines or drugs) is available for most of these diseases andvectorcontrolisstillthemainformofprevention. Thelimitationsoftraditionalinsecticide-based strategies, particularly the development of insecticide resistance, have resulted in significant efforts to develop alternative eco-friendly methods...
October 3, 2016: Insects
Marcela Montes de Oca, Rajiv Kumar, Fabian de Labastida Rivera, Fiona H Amante, Meru Sheel, Rebecca J Faleiro, Patrick T Bunn, Shannon E Best, Lynette Beattie, Susanna S Ng, Chelsea L Edwards, Glen M Boyle, Ric N Price, Nicholas M Anstey, Jessica R Loughland, Julie Burel, Denise L Doolan, Ashraful Haque, James S McCarthy, Christian R Engwerda
The development of immunoregulatory networks is important to prevent disease. However, these same networks allow pathogens to persist and reduce vaccine efficacy. Here, we identify type I interferons (IFNs) as important regulators in developing anti-parasitic immunity in healthy volunteers infected for the first time with Plasmodium falciparum. Type I IFNs suppressed innate immune cell function and parasitic-specific CD4(+) T cell IFNγ production, and they promoted the development of parasitic-specific IL-10-producing Th1 (Tr1) cells...
October 4, 2016: Cell Reports
Anthony D Harries, Amitabh B Suthar, Kudakwashe C Takarinda, Hannock Tweya, Nang Thu Thu Kyaw, Katie Tayler-Smith, Rony Zachariah
The international community has committed to ending the epidemics of HIV/AIDS, tuberculosis, malaria, and neglected tropical infections by 2030, and this bold stance deserves universal support. In this paper, we discuss whether this ambitious goal is achievable for HIV/AIDS and what is needed to further accelerate progress. The joint United Nations Program on HIV/AIDS (UNAIDS) 90-90-90 targets and the related strategy are built upon currently available health technologies that can diagnose HIV infection and suppress viral replication in all people with HIV...
2016: F1000Research
Masanori Yagi, Nirianne M Q Palacpac, Kazuya Ito, Yuko Oishi, Sawako Itagaki, Betty Balikagala, Edward H Ntege, Adoke Yeka, Bernard N Kanoi, Osbert Katuro, Hiroki Shirai, Wakaba Fukushima, Yoshio Hirota, Thomas G Egwang, Toshihiro Horii
The malaria vaccine BK-SE36 is a recombinant protein (SE36) based on the Honduras 1 serine repeat antigen-5 of Plasmodium falciparum, adsorbed to aluminium hydroxide gel. The phase Ib trial in Uganda demonstrated the safety and immunogenicity of BK-SE36. Ancillary analysis in the follow-up study of 6-20 year-old volunteers suggest significant differences in time to first episodes of clinical malaria in vaccinees compared to placebo/control group. Here, we aimed to get further insights into the association of anti-SE36 antibody titres and natural P...
October 5, 2016: Scientific Reports
Boris Prinz, Katherine L Harvey, Louisa Wilcke, Ulrike Ruch, Klemens Engelberg, Laura Biller, Isabelle Lucet, Steffen Erkelenz, Dorothee Heincke, Tobias Spielmann, Christian Doerig, Conrad Kunick, Brendan S Crabb, Paul R Gilson, Tim W Gilberger
Central to the pathogenesis of malaria is the proliferation of Plasmodium falciparum parasites within human erythrocytes. Parasites invade erythrocytes via a coordinated sequence of receptor-ligand interactions between the parasite and host cell. One key ligand, Apical Membrane Antigen 1 (AMA1), is a leading blood-stage vaccine and previous work indicates that phosphorylation of its cytoplasmic domain (CPD) is important to its function during invasion. Here we investigate the significance of each of the six available phospho-sites in the CPD...
October 4, 2016: Scientific Reports
Paul Spearman, Mark Mulligan, Evan J Anderson, Andi L Shane, Kathy Stephens, Theda Gibson, Brooke Hartwell, Drew Hannaman, Nora L Watson, Karnail Singh
: Plasmodium falciparum malaria is one of the leading infectious causes of childhood mortality in Africa. EP-1300 is a polyepitope plasmid DNA vaccine expressing 38 cytotoxic T cell epitopes and 16 helper T cell epitopes derived from P. falciparum antigens expressed predominantly in the liver phase of the parasite's life cycle. We performed a phase 1 randomized, placebo-controlled, dose escalation clinical trial of the EP-1300 DNA vaccine administered via electroporation using the TriGrid Delivery System device (Ichor Medical Systems)...
September 30, 2016: Vaccine
Martha Sedegah, Bjoern Peters, Michael R Hollingdale, Harini D Ganeshan, Jun Huang, Fouzia Farooq, Maria N Belmonte, Arnel D Belmonte, Keith J Limbach, Carter Diggs, Lorraine Soisson, Ilin Chuang, Eileen D Villasante
A DNA prime/adenovirus boost malaria vaccine encoding Plasmodium falciparum strain 3D7 CSP and AMA1 elicited sterile clinical protection associated with CD8+ T cell interferon-gamma (IFN-γ) cells responses directed to HLA class 1-restricted AMA1 epitopes of the vaccine strain 3D7. Since a highly effective malaria vaccine must be broadly protective against multiple P. falciparum strains, we compared these AMA1 epitopes of two P. falciparum strains (7G8 and 3D7), which differ by single amino acid substitutions, in their ability to recall CD8+ T cell activities using ELISpot and flow cytometry/intracellular staining assays...
2016: PloS One
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