Download or read book Studies of Naturally Acquired Antibody Responses to Plasmodium Falciparum Merozoite Surface Proteins in Malaria Endemic Populations written by Simon Weisman and published by . This book was released on 2003 with total page 372 pages. Available in PDF, EPUB and Kindle. Book excerpt:
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 Naturally Acquired Antibodies to P Falciparum Merozoite Surface Protein 3 MSP 3 and Glutamate rich Protein GLURP in Malaria Endemic Population in Thailand written by Pitchapa Yungyuen and published by . This book was released on 2002 with total page 202 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Bead based Chemistries to Quantitate Antibody Responses to Multiple Plasmodium Falciparum and Plasmodium Vivax Antigens written by Sonam Kaur Ghag and published by . This book was released on 2019 with total page 122 pages. Available in PDF, EPUB and Kindle. Book excerpt: Each year malaria impacts approximately 219 million people and causes over 400,000 deaths. The worldwide parasite burden remains high, even with the availability of efficacious antimalarial drugs and vector control tools such as insecticides and bed nets. Despite large investments in malaria vaccine development, there is currently no deployable vaccine for malaria. However, individuals who live in malaria endemic regions develop naturally acquired immunity (NAI). Thus, good vaccine candidates may be identified by studying serum antibody responses in malaria patients who live in endemic areas. Protein arrays, which interrogate patient serum antibody binding to many proteins simultaneously, are the primary method of antigen prioritization. However, protein arrays are fabricated by generating unpurified malaria antigens in bacteria and directly spotting lysates onto slides without validation of correct antigen folding or purification. Results from protein arrays can be affected by the sample impurity where positive binding events may be masked by background protein interactions or unrecognizable epitope presentation. Thus, technical improvements are needed to control protein production and protein exposure to patient sera. More recently, multiplexing bead-based assays have been applied to investigate malaria patient immune responses where spectrally distinct bead sets are coated with unique antigens of interest. For such assays, antigens traditionally are individually purified before coupling onto beads. To produce a more high-throughput method of patient immune response dissection using a large panel of antigens, bead-based chemistries were developed to modify multiplexing beads with a small linker molecule or with antigen capturing antibody. These modified beads capture malaria antigens directly from translation lysates, essentially purifying antigens in a single step. Both chemistries utilized the capture of recombinant antigens via a highly specific protein tag, HaloTag or C-tag. Although both systems successfully capture tagged antigens from translation lysates, the C-tag capture system proved to be more reliable and reproducible. Using recombinant malaria antigen merozoite surface protein 1 (MSP1)-coated beads and standard anti-MSP1 detecting antibodies, a 105-fold signal increase was observed in comparison to green fluorescence protein (GFP)-coated beads. Malaria patient sera responses to recombinant MSP1 were also measured. When assessed against MSP1-coated beads, serum from a high immune responsive patient gave an 8.5-fold increase in comparison to GFP-coated beads, while a low immune responsive patient gave a 2-fold increase. These results agree with previously reported protein microarray dissection of the same patient serum samples. The bead chemistries developed here make it possible to interrogate multiple malaria antigens simultaneously without demanding timely antigen purification. Furthermore, the multiplexing assay present antigen epitopes in a more accessible configuration while utilizing small amount of precious patient sera. The platform developed here will provide a high-throughput method of identifying specific patient antibody-antigen binding events and has the potential to customize bead arrays to model populations with high antigenic variation.
Download or read book Malaria written by Institute of Medicine and published by National Academies Press. This book was released on 1991-02-01 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is making a dramatic comeback in the world. The disease is the foremost health challenge in Africa south of the Sahara, and people traveling to malarious areas are at increased risk of malaria-related sickness and death. This book examines the prospects for bringing malaria under control, with specific recommendations for U.S. policy, directions for research and program funding, and appropriate roles for federal and international agencies and the medical and public health communities. The volume reports on the current status of malaria research, prevention, and control efforts worldwide. The authors present study results and commentary on the: Nature, clinical manifestations, diagnosis, and epidemiology of malaria. Biology of the malaria parasite and its vector. Prospects for developing malaria vaccines and improved treatments. Economic, social, and behavioral factors in malaria control.
Download or read book Antibody Responses to and the Structure of Plasmodium Falciparum Merozoite Surface Protein 1 written by Jose Alejandro Guevara-Patino and published by . This book was released on 1998 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Murine and Human Antibody Responses to Plasmodium Falciparum Merozoite Surface Protein 1 written by and published by . This book was released on 2004 with total page 496 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Naturally Acquired Immunity to Plasmodium Falciparum Malaria written by and published by . This book was released on 2013 with total page 61 pages. Available in PDF, EPUB and Kindle. Book excerpt:
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 The Impact of the C terminal Conserved Region of Plasmodium Falciparum s Merozoite Surface Protein 1 and Within host Diversity on Naturally Acquired Immunity to Malaria written by OraLee H. Branch and published by . This book was released on 2001 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Preclinical Assessment of the Immunogenicity Durability and Efficacy Induced by Pre erythrocytic Vaccines Against Plasmodium Falciparum Malaria written by Hayley Klingenberg and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is an ongoing global health problem caused by Plasmodium parasites that results in the death of over half a million people each year. The majority of these deaths occur in children under five years old who lack memory immune responses to protect them from infection. A major step towards prevention of malaria is through vaccination with RTS,S, the only WHO approved vaccines to date. RTS,S contains a portion of the central repeat region and the C-terminus of the pre-erythrocytic stage Plasmodium falciparum circumsporozoite protein (PfCSP). CSP is essential for sporozoite entry into hepatocytes making it a strong vaccine target. Naturally acquired and vaccine-induced immune responses towards this protein have been associated with protection against infection. Pre-erythrocytic stage vaccines aim to clear sporozoites and prevent progression to the blood-stage of the infection, which is the cause of disease pathology. RTS,S makes use of a Hepatitis B surface antigen (HbsAg) carrier to help improve immunogenicity and vaccine delivery. Extensive clinical trials have found that immunization with RTS,S results in low vaccine efficacy that wanes over time. This study aimed to improve upon the specificity, efficacy, and durability of RTS,S through the inclusion of the N-terminal region of PfCSP and the use of a Plasmodium-specific carrier protein. This project extended prior work that assessed the magnitude, specificity, and avidity of the antibody response induced by immunization with four novel PfCSP-based vaccine constructs adjuvanted with glucopyranosyl lipid adjuvant (GLA-SE). Three out of four of our constructs are fused to the blood stage protein, merozoite surface protein 8 (PfMSP8), which has been shown to improve the production and immunogenicity of other Plasmodium protein-based vaccines. The focus of the current thesis project was to assess the T cell responses, epitope recognition, antibody persistence and protective efficacy in vivo of our novel recombinant PfCSP-based vaccines. We demonstrate that inclusion of the N-terminal domain of PfCSP broadens the antibody response to include recognition of known linear B cell epitopes. Vaccination with our constructs drives robust antibody responses to conformational C-terminal epitopes as well as high anti-PfCSP antibody titers that remain durable for at least 6 months. Our constructs induce strong T cell responses, measured by the production of IFN-[gamma] by stimulated splenocytes, but this response shifts in specificity away from PfCSP towards PfMSP8 when mice were immunized with our fused chimeric constructs. However, this did not impact overall efficacy, as immunization with our chimeric PfCSP/8 construct resulted in significant protection against blood stage infection in mice when challenged intravenously with transgenic P. yoelii sporozoites that express PfCSP. These data demonstrate improvements over RTS,S and warrant further testing of the chimeric PfCSP/8 construct for use in a multivalent vaccine for P. falciparum malaria.
Download or read book Immune Response to Plasmodium Falciparum Merozoite Protein 2 written by Afra Khosravi and published by LAP Lambert Academic Publishing. This book was released on 2012-02 with total page 240 pages. Available in PDF, EPUB and Kindle. Book excerpt: Merozoite surface protein is a promising vaccine candidate of malaria on which many cross-sectional or longitudinal research has been done so far.The Antibody to a merozoite surface antigen-2 of plasmodium falciparum malaria is age dependent and mostly against the central variable domains of this antigen so called domains 2 and 3. such Immunity can lead to a protective response against the severe form of malaria disease.
Download or read book Parasite Genomics written by Luis M. de Pablos and published by Humana. This book was released on 2021-07-28 with total page 336 pages. Available in PDF, EPUB and Kindle. Book excerpt: This detailed book provides a comprehensive series of innovative research techniques and methodologies applied to the parasite genomics research area, all applying different approaches to analyzing parasite genomes and furthering the study of genetic complexity and the mechanisms of regulation. Beginning with chapters on novel sequencing and the bioinformatics pipeline, the volume continues by exploring diagnostic approaches using genomic tools, host-parasite interactions, as well as the genomics of parasite-derived extracellular vesicles. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Parasite Genomics: Methods and Protocols creates a detailed picture of genomic approaches for researchers seeking a better understanding of characterizing parasite nucleic acid content.
Download or read book World Malaria Report 2018 written by World Health Organization and published by World Health Organization. This book was released on 2019-02-12 with total page 210 pages. Available in PDF, EPUB and Kindle. Book excerpt: This year s report shows that after an unprecedented period of success in global malaria control progress has stalled. Data from 2015?2017 highlight that no significant progress in reducing global malaria cases was made in this period. There were an estimated 219 million cases and 435 000 related deaths in 2017. The World malaria report 2018 draws on data from 90 countries and areas with ongoing malaria transmission. The information is supplemented by data from national household surveys and databases held by other organizations.
Download or read book Detection of Anti Malarial Igg Igg Subclasses in Sudanies Patients written by Mona Mohamed El.Toum El.Sheisk and published by LAP Lambert Academic Publishing. This book was released on 2011-03 with total page 68 pages. Available in PDF, EPUB and Kindle. Book excerpt: Merozoite surface protein MSP2 is avaccine candidate antigen of Plasmodium falciparum that is polymorphic in natural populations. In this study we aimed to investigate whether malaria infection in associated with anti-malaria specific IgG, using recombinant proteins derived from the two major allelic types of MSP2 and ABO blood group. The conclusion is the Higher anti-malarial IgG1, IgG3, IgG2 and lower levels of IgG4 were associated with reduced risk of malaria infection. IgG2 is activator of the classical complement pathway, Fc RIIa H131 is essential for handling IgG2 immune complexes. These data suggest that an MSP2 based vaccine should be designed to induce high level antibody responses against the different MSP2 types present globally in P. falciparum populations and that MSP2 could be combined with other P. falciparum antigens to form a multi-component malaria vaccine.
Download or read book Complement and Antibody mediated Enhancement of Red Blood Cell Invasion by Plasmodium Falciparum written by Sergei Biryukov and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Plasmodium falciparum malaria is responsible for close to one million deaths worldwide each year. The Plasmodium life cycle involves invasion of hepatocytes and erythrocytes. The repeating cycle of erythrocyte invasion and destruction is the root cause of the morbidity and mortality brought about by the pathogen. Development of naturally acquired immunity against the parasite is an extremely slow process taking years to decades to develop, and it does not seem to result in sterile immunity. Attempts to develop a vaccine to block erythrocyte invasion have proven unsuccessful. Clinical data have demonstrated the development of a strong humoral immune response in vaccinated individuals. Although antibodies raised against vaccine antigens inhibit invasion in vitro in the presence of heat-inactivated (HI) serum, there is poor efficacy in vivo. The reasons for this discrepancy are unknown. A number of studies, in both humans and animal models, have shown that the complement cascade is activated during malaria infection. We hypothesize that complement activation and opsonization of merozoites enhances complement receptor 1 (CR1)-mediated invasion of erythrocytes. If we are correct, the parasite can hijack this arm of the innate immune response for its own benefit, avoiding or diminishing the efficacy of antibodies. We tested this hypothesis by studying the effect of mouse monoclonal anti-merozoite surface protein 1 (MSP-1) antibody 5.2 (mAb5.2) and antibodies from recipients of a merozoite vaccine (MSP142) for their ability to enhance or inhibit invasion in a complement-dependent manner. We carried out invasion assays with the above antibodies with appropriate controls in fresh or HI serum, or in complement-depleted or reconstituted serum. In addition, we tested the relevance of the CR1 pathway by inhibiting with sCR1. Invasion of erythrocytes was enhanced by fresh serum relative to 3 min, 5 min, or 30 min HI serum. Furthermore, addition of mAb5.2 to fresh serum increased the enhancement effect. Addition of C2 and Factor B to 3 min HI serum, but not to 30 min, rescued the enhancement of invasion in the presence of mAb5.2. Likewise, Compstatin, a C3 specific inhibitor, and sCR1 negated the enhancing affects of mAb5.2 in fresh serum but not that of fresh serum alone. Furthermore, soluble CR1 had invasion inhibitory activity in 3 min HI serum that was independent of antibody. Purified antibodies from MSP-1 vaccinees showed inhibitory activity in C3/C4 inactivated serum, but inhibition was drastically reduced in C3/C4 reconstituted serum. Passive transfer of anti-P. berghei antibodies into wild type mice enhanced parasitemia in an inverse dose-dependent manner. In addition, C3-deficient mice showed decreased parasite growth relative to wild type mice. In addition, we utilized erythrocytes from individuals with paroxysmal nocturnal hemoglobinuria (PNH), which results in the absence of glycosylphosphatidylinositol (GPI)-anchored receptors, in an effort to identify novel receptors utilized by the parasite for erythrocyte invasion. We found that PNH RBCs were invaded less effectively than wild type RBCs. Therefore, we carried out growth and invasion assays with anti-GPI erythrocyte receptor antibodies against six potential targets with appropriate controls in fresh or HI serum, or in complement-depleted or reconstituted serum. We identified Semaphorin-7A (SEMA7A) as a potential erythrocyte receptor that may interact with complement in promoting erythrocyte invasion by merozoites. Our results demonstrate that merozoites can highjack the complement system to their own advantage in a number of ways. Activation of the complement cascade via the classical pathway can allow merozoites to bind to CR1 and invade via this pathway. In addition, in the absence of antibodies, activation of the mannose binding lectin pathway by default may allow merozoites to bind to other complement receptors on the RBC that mediate invasion. Such mechanisms could explain or contribute to the low efficacy of vaccine-induced anti-merozoite antibodies to block invasion in vivo. These findings are of great importance to the efforts to develop a merozoite blocking vaccine.
Download or read book Cumulated Index Medicus written by and published by . This book was released on 2000 with total page 1836 pages. Available in PDF, EPUB and Kindle. Book excerpt:
