Download or read book Production of a Recombinant E Coli Expressed Malarial Vaccine from the C Terminal Fragment of Plasmodium Falciparum 3D7 Merozoite Surface Protein 1 written by and published by . This book was released on 2000 with total page 30 pages. Available in PDF, EPUB and Kindle. Book excerpt: P. falciparum Merozoite Surface Protein-1 (MSP-1) is a leading erythrocytic stage vaccine candidate. Following secondary proteolytic processing, it may play a role in binding and/or invasion of erythrocytes. The secondary processing gives a 33kD and 19kD fragment. The MSP1-19 is a target for parasite inhibitory antibodies and protective immunity. However, it appears to lack T-helper epitopes. Since antibody is likely the effector mechanism induced by MSP1-19, it is important to insure that recombinant vaccines based on this antigen be folded correctly and contain T-helper epitopes that will enhance induction of humoral responses. We have developed recombinant MSP1-42 molecules that are structurally correct based on positive reactivities with conformation-dependent mAbs. These proteins have been produced to greater than 95% purity and exceed FDA endotoxin standards. Immunogenicity studies in mice and Rhesus monkeys reveal that good antibody responses are induced to MSP1-42 when these animals are immunized with the MSP1-42 plus SBAS2 adjuvant.

Download or read book Production of a Recombinant E Coli Expressed Malaria Vaccine from the C Terminal Fragment of Piasmodium Falciparum 3D7 Merozoite Surface Protein 1 written by and published by . This book was released on 1999 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malarial blood stage antigens can produce humoral immunity by induction of protective antibodies to epitopes on surface antigens on parasites. The merozoite surface protein-1 (MSP1) of P. falciparum is a major blood-stage vaccine candidate. MSP1 may play a role in binding and/or infection of erythrocytes by merozoites (parasites) during red blood cell invasion. The C-terminal fragment of MSP1, MSP1(sub 19), is highly conserved among all known strains of P. falciparum. immunization with recombinant proteins that have native-like conformations may elicit long-lasting protective immunity that mimics the natural immunity. We have used bacterial expression to tightly regulate transcription and translation of MSP1(sub 42). Plasmids that encode MSP1(sub 42) were prepared and tested for their ability to express recombinant protein. A three column purification scheme that included Ni(+2) metal chelate chromatography, anion and then cation exchange chromatography, yielded greater than 95% pure MSP1(sub 42). Immunoreactivity with mAbs showed that recombinant MSP1(sub 42) was conformationally similar to native MSP1. The objectives were to develop recombinant MSP1(sub 42) molecules that were structurally correct, to develop fermentation and purification processes that could be scaled-up for large-scale processes, and ultimately, to advance these products into human clinical trials.

Download or read book Development of Recombinant Expression Systems for the Production of Malaria Antigens written by and published by . This book was released on 1998 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malarial erythrocytic-stage antigens produce humoral immunity by inducing protective antibodies to epitopes on surface antigens on the parasites. The merozoite surface protein-1 (MSP1) of P. falciparum is a major malaria erythrocytic-stage vaccine candidate. MSP1 may play a role in binding and/or infection of erythrocytes by merozoites (parasites) during red blood cell invasion. The C-terminal fragment of MSP1, MSP1(42), is highly conserved among all known strains of P. falciparum. However, it is folded into a complex structure containing six possible disulfide bridges. Immunization with recombinant proteins that have native-like conformations may elicit long-lasting protective immunity that mimics the natural development of humoral immunity. We have used a novel bacterial expression system that utilizes tightly regulatable transcription and translation signals to control expression of potentially toxic heterologous proteins. Several plasmids encoding MSP1(42) were constructed and tested for their ability to express recombinant protein. These constructs were designed for purification using Ni(+2)-chelating chromatography. Our results show that the recombinant proteins contained conformationally similar structures to the native parasites. The objectives were to develop recombinant MSP1(42) molecules that were structurally correct, (b) to develop fermentation and purification processes that could be scaled-up for large-scale processes, and ultimately (c) to advance these products into human clinical trials.

Download or read book Expression Systems written by Michael R. Dyson and published by Methods Express (Hardcover). This book was released on 2007 with total page 318 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein expression is an increasingly important tool for research on gene function. What is needed is not just a lab manual providing established methods as well as the latest state-of-the-art protocols, but also clear advice on what expression system to choose when. Expression Systems: Methods Expressuniquely fills this need. It covers expression across a broad range of systems, including the following. *Baculovirus expression vectors *CHO cells *E. coli *HEK293-EBNA1 cells *Lactococcus lactis and other gram positive bacteria *S. cerevisiae *transfected insect cells *Pichia pastoris *mammalian cells using BacMam viruses *lentiviral vectors *wheat germ cell-free system The book takes the reader through how to make an informed choice of appropriate system, taking into account the protein target, the time involved, the ultimate use of the expressed protein, and the laboratory equipment required. It also provides step-by-step methods for each system. In addition, the book describes the optimisation of expression strategies, expression engineering using ribosome display, and how to select protein variants with improved expression. Every chapter discusses the merits and limitations of the approaches available, describes the key techniques in full practical detail, and provides sensible advice for immediate use at the bench. In summary, Expression Systems: Methods Expressis a comprehensive laboratory manual and information resource for researchers at all levels, from postgraduate student to principal investigator.

Download or read book Purification and Characterization of a Malaria Vaccine Candidate written by Fei Fei Miu and published by . This book was released on 2003 with total page 250 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Malaria Immunology written by Peter Perlmann and published by Karger Medical and Scientific Publishers. This book was released on 2002-01-01 with total page 422 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite extensive efforts to control it, malaria is still one of the most devastating infectious diseases worldwide. This book, now in its second edition, provides a broad and up-to-date overview of the rapidly expanding field of malaria immunology and its importance in the control of this disease. The first section deals with the malaria parasite and its interactions with both the vertebrate host and the mosquitoes which transmit the disease. In the second part, the mechanisms of immunity and their regulation by environmental and genetic factors are discussed. Finally, this volume contains several chapters on malaria vaccine development, describing the application of the most recent vaccine technologies as well as ongoing and planned vaccine trials. Authored by well-recognized experts, this volume not only demonstrates the rapid progress being made in the search for vaccines against malaria, but also broadens our understanding of immunity to infection in general. It is therefore highly recommended reading for all scientists and professionals in the fields of immunology, infection and vaccine development.

Download or read book Recombinant Production Characterization and Immunogenicity of Malaria Vaccine Candidates Expressed in Bacillus Subtilis written by Chitti Babu Gottimukkala and published by . This book was released on 2014 with total page 446 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is an infectious disease transmitted by mosquitoes. This disease is endemic to tropical countries. Approximately three billion people (living in more than 100 countries) are at risk of malaria with 200 million cases per year and nearly 700,000 deaths-mainly in children under the age of five. The parasite species P. falciparum is the predominant cause of malaria deaths in humans. Mortality and morbidity due to the disease have been showing detrimental effect on economies. Although drugs are available for the treatment of malaria, they are expensive; furthermore resistance to these drugs is widespread. Various control measures such as environmental modifications to prevent mosquito breeding, impregnated bed nets, artemisinin combination therapy have reduced the burden of malaria in the past decade. However, sustained control requires the development of additional tools including a protective vaccine. Various proteins taken from the parasite's life cycle have been demonstrated to be potential vaccine candidates, and are in various stages of clinical trials. Asexual blood stage of parasite's life cycle is the reason for morbidity and mortality. Therefore vaccines against this stage are necessary to control the infection. Previous work suggested that a vaccine including multiple antigens from the parasite's life cycle can be more effective than vaccine formulations containing a single antigen type. In this work, a set of potential vaccine candidates has been chosen to develop an efficacious vaccine. They are Plasmodium falciparum merozoite surface protein 119 (PfMSP119), 4 (PfMSP4), and 5 (PfMSP5). The selected vaccine candidates play an important role in erythrocyte invasion. Specific antibodies against these proteins inhibited parasite growth in in vitro experiments, and passively transferred antibodies showed in vivo growth inhibition. These proteins contain one or more cysteine rich EGF-like domains, which are conserved in all malaria species. Therefore, the functional form- vaccine candidates containing correctly folded EGF-like domains, are essential to induce specific antibodies which can inhibit parasite growth, and thus, malaria. One more candidate Plasmodium yoelii merozoite surface protein 4/5 (PyMSP4/5) has been selected. PyMSP4/5 is a single homologue of two potential human malaria vaccine candidates and it causes malaria in rodents. Therefore, it is a useful target to study the protection efficacy of the vaccine using mouse model.Falciparum malaria is most prevalent in developing countries and this in turn demands the requirement for safe and low-cost vaccines. A majority of available expression hosts: prokaryotic as well as eukaryotic systems failed to produce or yielded very low amounts. We have been seeking alternative expression systems that can overcome some of the bottlenecks and allow subunit production at low cost and large scale. In the present study, we have attempted to use an alternative expression host, Bacillus subtilis, for the production of malaria vaccine candidates.B. subtilis is a non-pathogenic, gram positive organism, which is known for its ability to secrete target proteins and has the advantage of well established methods for scale-up. Vaccine candidates were secreted into the culture medium at higher yields. Characterization studies including SDS-PAGE, mass spectrometry and N-terminal sequencing indicated the secretion of near full-length protein. Recombinant proteins as vaccines are poor in eliciting an immune response and they are required to be presented with an adjuvant, which can boost both humoral and cellular immune responses. Currently, alum is the only approved adjuvant for human, induces a good Ab (Th2) response, but poorly stimulates the strong cellular (Th1) immune response. Bacterial flagellin (FljB) is one of the potential protein adjuvants that has been chosen to boost the malarial vaccine formulation.Purified proteins emulsified with Freund's adjuvant and mixed/conjugated with flagellin induced strong immune responses in mice following intraperitoneal injection. The mean titer values obtained were higher than those obtained with an equivalent dose of purified E. coli-derived proteins, suggesting that B. subtilis expressed malarial antigens are more immunogenic than those produced by E. coli. The mouse antibodies raised against B. subtilis produced malaria vaccine candidates were reactive to native parasite proteins as evident from immunoblotting on parasite lysate and indirect immunofluorescence assays of fixed parasites. Other advantages of this system over traditional expression methods included a higher level of full-length protein, decreased multimer formation and a simplified downstream processing procedure. All the above features are essential to formulate an effective malaria vaccine or any other high quality clinical material. Therefore, B. subtilis seems to be a valuable advance in the quest to produce an efficacious and cost effective malaria vaccine.

Download or read book Advances in Malaria Research written by Deepak Gaur and published by John Wiley & Sons. This book was released on 2016-12-27 with total page 611 pages. Available in PDF, EPUB and Kindle. Book excerpt: Thoroughly reviews our current understanding of malarial biology Explores the subject with insights from post-genomic technologies Looks broadly at the disease, vectors of infection, and treatment and prevention strategies A timely publication with chapters written by global researchers leaders

Download or read book Malaria written by Maria M. Mota and published by Springer. This book was released on 2017-01-12 with total page 275 pages. Available in PDF, EPUB and Kindle. Book excerpt: Currently, malaria kills more than 300,000 people per year, making it a top priority of world leaders and international organizations, who are working towards implementing and coordinating efforts to eradicate this disease. An effective malaria vaccine is recognized as the key element that will decide between success and failure in this fight. At present, despite intensive research efforts, such a vaccine is not yet available for use. However, there are a number of advanced candidate vaccines with high chances of success in the short term. Malaria: Immune Response to Infection and Vaccination provides a comprehensive view on the immune response to malaria and to the different vaccines under development. The book offers the following: - Contributions by top research leaders in the field, - Comparisons of the immune responses to both malaria infection and malaria vaccines, which are traditionally treated separately, - Coverage of the immune responses to the different stages of malaria, which are frequently treated as separate fields of research.

Download or read book Nanomaterials for Food Applications written by and published by Elsevier. This book was released on 2018-11-16 with total page 446 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nanomaterials for Food Applications highlights recent developments in nanotechnologies, covering the different food areas where these novel products or technologies can be applied. The book covers five major themes, showing how nanotechnology is used in food, the use of ingredients in nanoform to improve bioavailability or nanoencapsulation technologies, nanotechnologies for food processing, nanosensors for food quality and safety, nanotechnologies for food packaging, and methods to evaluate potential risks and regulatory issues. This is an important research reference that will be of great value to academic and industrial readers, as topics of importance, both at a research level and for commercial applications, are covered. Regulatory agencies will also be interested in the latest developments covered in the book as they will help set the foundation for further regulations. Demonstrates how nanotechnology can improve food quality and safety Shows how nanotechnology is used to create more effective food processing techniques Discusses the regulatory issues surrounding the use of nanomaterials in food to ensure they are used safely and responsibly

Download or read book Design Production and Evaluation of a Plasmodium Falciparum Merozoite Surface Protein 2 based Vaccine for Inclusion in a Multivalent Formulation Targeting Multiple Parasite Stages written by Jacqueline Schneider Eacret and published by . This book was released on 2019 with total page 229 pages. Available in PDF, EPUB and Kindle. Book excerpt: Development of a highly efficacious vaccine will be necessary for malaria elimination. Studies in Plasmodium falciparum endemic areas indicate that naturally acquired antibody responses to MSP2 are associated with resistance to malaria, making PfMSP2 an attractive vaccine candidate. To overcome challenges encountered with subunit malaria vaccines, we established that the use of highly immunogenic rPfMSP8 as a carrier protein for vaccine candidates rPfMSP119 and rPfs25 facilitated production, minimized antigenic competition and enhanced induction of functional antibodies. Here, we exploited the benefits of our rPfMSP8 fusion partner to optimize a rPfMSP2-based subunit vaccine. A synthetic PfMSP2 (3D7) codon harmonized gene was used to produce unfused rPfMSP2 or chimeric rPfMSP2/8 in E. coli. Purified, rPfMSP2 formed amyloid-like fibrils in vitro, however rPfMSP2/8 did not. Immunization of rabbits and mice with both rPfMSP2 antigens elicited high titer anti-PfMSP2 antibodies that recognized the major allelic variants of native PfMSP2. Competition assays revealed differences in antibody specificities induced by the two rPfMSP2-based vaccines, with evidence of epitope masking by rPfMSP2-associated fibrils. Immunogenicity studies in mice demonstrated that formulation of rPfMSP2 vaccines with GLA-SE, a synthetic TLR4 agonist, elicited cytophilic IgG isotypes and production of Th1-associated cytokines. T cell responses were specific for epitopes within PfMSP2 and PfMSP8 domains. The rPfMSP2/8 + GLA-SE formulation induced significantly higher antibody titers with superior durability and capacity to opsonize P. falciparum merozoites for phagocytosis. Immunization with a trivalent vaccine including PfMSP2/8, PfMSP1/8 and Pfs25/8 induced high levels of antigen-specific antibody, with no evidence of antigenic competition. These results are highly encouraging for the addition of rPfMSP2/8 as a component of an efficacious, multivalent, multistage malaria vaccine.

Download or read book Innovations and Implementations of Computer Aided Drug Discovery Strategies in Rational Drug Design written by Sanjeev Kumar Singh and published by Springer Nature. This book was released on 2021-02-02 with total page 334 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents various computer-aided drug discovery methods for the design and development of ligand and structure-based drug molecules. A wide variety of computational approaches are now being used in various stages of drug discovery and development, as well as in clinical studies. Yet, despite the rapid advances in computer software and hardware, combined with the exponential growth in the available biological information, there are many challenges that still need to be addressed, as this book shows. In turn, it shares valuable insights into receptor-ligand interactions in connection with various biological functions and human diseases. The book discusses a wide range of phylogenetic methods and highlights the applications of Molecular Dynamics Simulation in the drug discovery process. It also explores the application of quantum mechanics in order to provide better accuracy when calculating protein-ligand binding interactions and predicting binding affinities. In closing, the book provides illustrative descriptions of major challenges associated with computer-aided drug discovery for the development of therapeutic drugs. Given its scope, it offers a valuable asset for life sciences researchers, medicinal chemists and bioinformaticians looking for the latest information on computer-aided methodologies for drug development, together with their applications in drug discovery.

Download or read book World Malaria Report 2019 written by World Health Organization and published by . This book was released on 2019-08-28 with total page 224 pages. Available in PDF, EPUB and Kindle. Book excerpt: The World Malaria Report 2019 provides a comprehensive update on global and regional malaria data and trends. The report tracks investments in malaria programs and research as well as progress across all intervention areas: prevention, diagnosis, treatment, elimination, and surveillance. It also includes dedicated chapters on the consequences of malaria on maternal infant and child health the "High Burden to High Impact" approach as well as biological threats to the fight against malaria. The 2019 report is based on information received from more than 80 countries and areas with ongoing malaria transmission. This information is supplemented by data from national household surveys and databases held by other organizations.

Download or read book Management of Severe Malaria written by World Health Organization and published by World Health Organization. This book was released on 2000-04 with total page 84 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria continues to be a major health problem in many parts of the world, with over 2,400 million people in 100 countries at risk of infection. This handbook is an updated edition of 'Management of severe and complicated malaria', providing practical guidance on the diagnosis and management of severe falciparum malaria, a form of the disease that can have life-threatening complications if treatment is delayed.

Download or read book Tropical Diseases written by Sangkot Marzuki and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 390 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tropical Diseases: From Molecule to Bedside covers a wide range of topics that reflect perspectives of northern and southern hemispheres. Fittingly, it defines tropical diseases in a broader-than-usual manner. The book discusses traditional tropical medicine topics of infectious diseases and nutritional deficiencies. These diseases are common in the tropics, although some are associated more with poverty than with tropical living conditions. It also deals with genetic diseases and genomic issues that are truly associated with living in the tropics, e.g. the thalassemias. The book begins with several papers describing the vast human genetic diversity of Southeast Asia and its relationship to several genetic disorders. These papers illustrate the future direction of genomic activities in relation to disease susceptibility and resistance. The next sections deal with malaria and four specific viral and bacterial diseases of the tropics: hepatitis B and C, tuberculosis, and leprosy, followed by a section on general bacterial infection. Two papers on nutrition complete the volume.

Download or read book Encyclopedia of Malaria written by and published by Springer. This book was released on 2018-07-12 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Encyclopedia of Malaria represents a vast databank of information about the study of malaria. It provides an overview of the historical, rapid and significant developments that have occurred in malaria research, including the 2002 genome sequencing of Plasmodium falciparum and its mosquito vector, Anopheles gambiae. This work provides a concise source of up-to-date research findings in the form of definitions and essays and present comprehensive coverage of topics from history to findings to diagnosis and treatment, written by recognized malaria researchers with practical experience. It appeals to a diverse audience, including malaria researchers, teachers, investigators and public health professionals.

Download or read book Comprehensive and Molecular Phytopathology written by Yuri Dyakov and published by Elsevier. This book was released on 2007-01-09 with total page 497 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book offers a collection of information on successive steps of molecular ‘dialogue’ between plants and pathogens. It additionally presents data that reflects intrinsic logic of plant-parasite interactions. New findings discussed include: host and non-host resistance, specific and nonspecific elicitors, elicitors and suppressors, and plant and animal immunity. This book enables the reader to understand how to promote or prevent disease development, and allows them to systematize their own ideas of plant-pathogen interactions. * Offers a more extensive scope of the problem as compared to other books in the market* Presents data to allow consideration of host-parasite relationships in dynamics and reveals interrelations between pathogenicity and resistance factors* Discusses beneficial plant-microbe interactions and practical aspects of molecular investigations of plant-parasite relationships* Compares historical study of common and specific features of plant immunity with animal immunity