Journal articles on the topic 'Malaria vaccine Synthesis'
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Clemente, Marina, and Mariana G. Corigliano. "Overview of Plant-Made Vaccine Antigens against Malaria." Journal of Biomedicine and Biotechnology 2012 (2012): 1–8. http://dx.doi.org/10.1155/2012/206918.
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This paper is an overview of vaccine antigens against malaria produced in plants. Plant-based expression systems represent an interesting production platform due to their reduced manufacturing costs and high scalability. At present, differentPlasmodiumantigens and expression strategies have been optimized in plants. Furthermore, malaria antigens are one of the few examples of eukaryotic proteins with vaccine value expressed in plants, making plant-derived malaria antigens an interesting model to analyze. Up to now, malaria antigen expression in plants has allowed the complete synthesis of these vaccine antigens, which have been able to induce an active immune response in mice. Therefore, plant production platforms offer wonderful prospects for improving the access to malaria vaccines.
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Ballou, W. R., J. Blood, T. Chongsuphajaissidhi, D. M. Gordon, D. G. Heppner, D. E. Kyle, C. Luxemburger, et al. "Field trials of an asexual blood stage malaria vaccine: studies of the synthetic peptide polymer SPf66 in Thailand and the analytic plan for a phase IIb efficacy study." Parasitology 110, S1 (March 1995): S25—S36. http://dx.doi.org/10.1017/s0031182000001463.
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SummarySeveral years ago the Walter Reed Army Institute of Research (WRAIR) initiated an independent analysis of the candidate malaria blood stage vaccine SPf66. WRAIR contracted for the synthesis and formulation of SPf66 in United States Food and Drug Administration (FDA) inspected laboratories within the U.S., and in 1992, filed an Investigational New Drug (IND) application with the FDA. Preclinical studies indicated that the vaccine could be synthesized to meet its release specifications, and when adjuvanted with alum, was essentially equivalent to Colombian produced SPf66 in regards to immunogenicity in preclinical studies of rodents and primates, and in human volunteers in Phase I studies. The goal of these efforts was ultimately to conduct a Phase IIb field trial to determine the safety and efficacy of SPf66 produced under current Good Manufacturing Practices (cGMP). Such a trial is currently underway in a malaria endemic refugee camp along the Thai–Burmese border. Here we briefly describe the study and present the formal analytic plan that was submitted to regulatory authorities in the United States for analysis of the study results. We believe such independent confirmatory studies are an essential part of the vaccine development process and are required to provide important data regarding the safety and efficacy of candidate vaccines in diverse geographical regions, and as a means to assess their role in the context of broader malaria control programmes.
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Moysa, A. A., and E. F. Kolesanova. "Synthetic peptide vaccines." Biomeditsinskaya Khimiya 57, no. 1 (January 2011): 14–30. http://dx.doi.org/10.18097/pbmc20115701104.
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This review considers the stages of the development of synthetic peptide vaccines against infectious agents, novel approaches and technologies employed in this process, including bioinformatics, genomics, proteomics, large-scale peptide synthesis, high-throughput screening methods, the use of transgenic animals for modelling human infections. An important role for the development and selection of efficient adjuvants for peptide immunogens is noted. Examples of synthetic peptide vaccine developments against three infectious diseases (malaria, hepatitis C, and foot-and-mouth disease) are given.
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Olugbile, S., C. Kulangara, G. Bang, S. Bertholet, E. Suzarte, V. Villard, G. Frank, et al. "Vaccine Potentials of an Intrinsically Unstructured Fragment Derived from the Blood Stage-Associated Plasmodium falciparum Protein PFF0165c." Infection and Immunity 77, no. 12 (September 28, 2009): 5701–9. http://dx.doi.org/10.1128/iai.00652-09.
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ABSTRACT We have identified new malaria vaccine candidates through the combination of bioinformatics prediction of stable protein domains in the Plasmodium falciparum genome, chemical synthesis of polypeptides, in vitro biological functional assays, and association of an antigen-specific antibody response with protection against clinical malaria. Within the predicted open reading frame of P. falciparum hypothetical protein PFF0165c, several segments with low hydrophobic amino acid content, which are likely to be intrinsically unstructured, were identified. The synthetic peptide corresponding to one such segment (P27A) was well recognized by sera and peripheral blood mononuclear cells of adults living in different regions where malaria is endemic. High antibody titers were induced in different strains of mice and in rabbits immunized with the polypeptide formulated with different adjuvants. These antibodies recognized native epitopes in P. falciparum-infected erythrocytes, formed distinct bands in Western blots, and were inhibitory in an in vitro antibody-dependent cellular inhibition parasite-growth assay. The immunological properties of P27A, together with its low polymorphism and association with clinical protection from malaria in humans, warrant its further development as a malaria vaccine candidate.
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Chandrudu, Saranya, Mariusz Skwarczynski, David Pattinson, Simon H. Apte, Denise L. Doolan, and Istvan Toth. "Synthesis and immunological evaluation of peptide-based vaccine candidates against malaria." Biochemical Compounds 4, no. 1 (2016): 1. http://dx.doi.org/10.7243/2052-9341-4-1.
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Joshi, Manju B., Albert A. Gam, Robert A. Boykins, Sanjai Kumar, John Sacci, Stephen L. Hoffman, Hira L. Nakhasi, and Richard T. Kenney. "Immunogenicity of Well-Characterized Synthetic Plasmodium falciparum Multiple Antigen Peptide Conjugates." Infection and Immunity 69, no. 8 (August 1, 2001): 4884–90. http://dx.doi.org/10.1128/iai.69.8.4884-4890.2001.
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ABSTRACT Given the emerging difficulties with malaria drug resistance and vector control, as well as the persistent lack of an effective vaccine, new malaria vaccine development strategies are needed. We used a novel methodology to synthesize and fully characterize multiple antigen peptide (MAP) conjugates containing protective epitopes fromPlasmodium falciparum and evaluated their immunogenicity in four different strains of mice. A di-epitope MAP (T3-T1) containing two T-cell epitopes of liver stage antigen-1 (LSA-1), a di-epitope MAP containing T-cell epitopes from LSA-1 and from merozoite surface protein-1, and a tri-epitope MAP (T3-CS-T1) containing T3-T1 and a potent B-cell epitope from the circumsporozoite protein central repeat region were tested in this study. Mice of all four strains produced peptide-specific antibodies; however, the magnitude of the humoral response indicated strong genetic restriction between the different strains of mice. Anti-MAP antibodies recognized stage-specific proteins on the malaria parasites in an immunofluorescence assay. In addition, serum from hybrid BALB/cJ × A/J CAF1 mice that had been immunized with the tri-epitope MAP T3-CS-T1 successfully inhibited the malaria sporozoite invasion of hepatoma cells in vitro. Spleen cells from immunized mice also showed a genetically restricted cellular immune response when stimulated with the immunogen in vitro. This study indicates that well-characterized MAPs combining solid-phase synthesis and conjugation chemistries are potent immunogens and that this approach can be utilized for the development of subunit vaccines.
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Hewitt, Michael C., Daniel A. Snyder, and Peter H. Seeberger. "Rapid Synthesis of a Glycosylphosphatidylinositol-Based Malaria Vaccine Using Automated Solid-Phase Oligosaccharide Synthesis." Journal of the American Chemical Society 124, no. 45 (November 2002): 13434–36. http://dx.doi.org/10.1021/ja027538k.
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Kanoi, Bernard N., Hikaru Nagaoka, Masayuki Morita, Takafumi Tsuboi, and Eizo Takashima. "Leveraging the wheat germ cell-free protein synthesis system to accelerate malaria vaccine development." Parasitology International 80 (February 2021): 102224. http://dx.doi.org/10.1016/j.parint.2020.102224.
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Kronenberger, Thales, Jasmin Lindner, Kamila A. Meissner, Flávia M. Zimbres, Monika A. Coronado, Frank M. Sauer, Isolmar Schettert, and Carsten Wrenger. "Vitamin B6-Dependent Enzymes in the Human Malaria ParasitePlasmodium falciparum: A Druggable Target?" BioMed Research International 2014 (2014): 1–11. http://dx.doi.org/10.1155/2014/108516.
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Malaria is a deadly infectious disease which affects millions of people each year in tropical regions. There is no effective vaccine available and the treatment is based on drugs which are currently facing an emergence of drug resistance and in this sense the search for new drug targets is indispensable. It is well established that vitamin biosynthetic pathways, such as the vitamin B6de novosynthesis present inPlasmodium, are excellent drug targets. The active form of vitamin B6, pyridoxal 5-phosphate, is, besides its antioxidative properties, a cofactor for a variety of essential enzymes present in the malaria parasite which includes the ornithine decarboxylase (ODC, synthesis of polyamines), the aspartate aminotransferase (AspAT, involved in the protein biosynthesis), and the serine hydroxymethyltransferase (SHMT, a key enzyme within the folate metabolism).
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Pfeiffer, Bernhard, Elisabetta Peduzzi, Kerstin Moehle, Rinaldo Zurbriggen, Reinhard Glück, Gerd Pluschke, and John A. Robinson. "A Virosome-Mimotope Approach to Synthetic Vaccine Design and Optimization: Synthesis, Conformation, and Immune Recognition of a Potential Malaria-Vaccine Candidate." Angewandte Chemie International Edition 42, no. 21 (May 30, 2003): 2368–71. http://dx.doi.org/10.1002/anie.200250348.
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Tsuboi, Takafumi, Satoru Takeo, Thangavelu U. Arumugam, Hitoshi Otsuki, and Motomi Torii. "The wheat germ cell-free protein synthesis system: A key tool for novel malaria vaccine candidate discovery." Acta Tropica 114, no. 3 (June 2010): 171–76. http://dx.doi.org/10.1016/j.actatropica.2009.10.024.
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Niyibizi, Jean Baptiste, Peter G. Kirira, Francis T. Kimani, Fiona Oyatsi, and Joseph K. Ng’ang’a. "Chemical Synthesis, Efficacy, and Safety of Antimalarial Hybrid Drug Comprising of Sarcosine and Aniline Pharmacophores as Scaffolds." Journal of Tropical Medicine 2020 (April 9, 2020): 1–12. http://dx.doi.org/10.1155/2020/1643015.
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Malaria is a disease caused by protozoans transmitted to humans by infected female Anopheles mosquitoes. According to the WHO report of 2015, there were 214 million cases of malaria with 438,000 deaths worldwide. Ninety percent of world’s malaria cases occur in Africa, where the disease is recognized as a serious impediment to economic and social development. Despite advancement in malaria research, the disease continues to be a global problem, especially in developing countries. Currently, there is no effective vaccine for malaria control. In addition, although there are effective drugs for treatment of malaria, this could be lost to the drug resistance in different Plasmodium species. The most lethal form is caused by P. falciparum which has developed resistance to many chemotherapeutic agents and possibly to the current drugs of choice. Reducing the impact of malaria is a key to achieving the sustainable development goals which are geared toward combating the disease. Covalent bitherapy is a rational and logical way of drug design which entails joining a couple of molecules with individual intrinsic action into a unique agent, hence packaging dual activity into one hybrid. This suggests the need to develop new antimalarial drugs that are effective against malaria parasites based on the new mode of action, molecular targets, and chemical structures. In silico studies have shown that sarcosine is able to bind to unique plasmodia proteins (P. falciparum ATCase), whereas aniline can be a ligand to target protein (enoyl acyl carrier protein reductase), hence suppressing the progression of the disease. The main objective of this study was to synthesize and determine the efficacy and safety of antiplasmodial hybrid drug comprising the sarcosine and aniline derivative for management of plasmodial infections. The hybrid drug was synthesized by adding thionyl chloride to sarcosine to form acyl chloride which was then added to aniline to form sarcosine-aniline hybrid molecule. The IC50 of sarcosine-aniline hybrid was 44.80 ± 4.70 ng/ml compared with that of aniline derivative which was 22.86 ± 1.26 ng/ml. The IC50 of control drugs was 2.63 ± 0.38 ng/ml and 5.69 ± 0.39 ng/ml for artesunate and chloroquine, respectively. There was a significant difference between IC50 of sarcosine-aniline hybrid and aniline derivative (p<0.05). There was also a significant difference between sarcosine-aniline hybrid and standard drugs used to treat malaria including artesunate and chloroquine (p<0.05). The ED50 of sarcosine-aniline hybrid drug was 6.49 mg/kg compared with that of aniline derivative which was 3.61 mg/kg. The ED50 of control drugs was 3.56 mg/kg, 2.94 mg/kg, and 1.78 mg/kg for artesunate-aniline hybrid, artesunate, and chloroquine, respectively. There was a significant difference (p<0.05) between ED50 of sarcosine-aniline hybrid and both controls such as aniline derivative, artesunate, artesunate-aniline hybrid, and chloroquine. Cytotoxicity results revealed that sarcosine-aniline hybrid was safe to vero cells with a CC50 of 50.18 ± 3.53 μg/ml. Sarcosine-aniline hybrid was significantly less toxic compared with artesunate, chloroquine, and doxorubicin. Sarcosine-aniline hybrid was efficacious and safe to mice. Therefore, covalent bitherapy should be used in drug development for drug resistance mitigation.
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Ibitokou, Samad, Brian E. Dillon, Mala Sinha, Bartosz Szczesny, Añahi Delgadillo, Doaa Reda Abdelrahman, Csaba Szabo, et al. "Early Inhibition of Fatty Acid Synthesis Reduces Generation of Memory Precursor Effector T cells in Chronic Infection." Journal of Immunology 200, no. 1_Supplement (May 1, 2018): 167.1. http://dx.doi.org/10.4049/jimmunol.200.supp.167.1.
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Abstract Understanding the mechanisms of CD4 memory T cell (Tmem) differentiation in malaria is critical for vaccine development. However, the metabolic regulation of CD4 Tmem differentiation is not clear, particularly in persistent infections. In this study, we investigated the role of fatty acid synthesis (FAS) in Tmem development in Plasmodium chabaudi chronic mouse malaria infection. We show that T cell-specific deletion, and early pharmaceutical inhibition of acetyl coA carboxylase 1, the rate limiting step of FAS, inhibit generation of early memory precursor effector T cells (MPEC). To compare the role of FAS during early differentiation or survival of Tmem in chronic infection, a specific inhibitor of acetyl coA carboxylase 1, 5-(Tetradecyloxy)-2-furoic acid, was administered at different times postinfection. Strikingly, the number of Tmem was only reduced when FAS was inhibited during T cell priming, but not during the Tmem survival phase. FAS inhibition during priming increased effector T cells (Teff) proliferation, and strongly decreased peak parasitemia, which is consistent with improved Teff function. Conversely, MPEC were decreased, in a T cell-intrinsic manner, upon early FAS inhibition in chronic, but not acute, infection. Early cure of infection also increased mitochondrial volume in Tmem compared to Teff, supporting previous reports in acute infection. We demonstrate that the MPEC-specific effect was due to the higher fatty acid content and synthesis in MPEC compared to terminally differentiated Teff. In conclusion, FAS in CD4 T cells regulates the early divergence of Tmem from Teff in chronic infection.
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Pawana, Nuryatmaja Gora, Kahar Muzakhar, and Kartika Senjarini. "Isolation of Genes Encoding Arthropod Odorant Binding Proteins (OBP), D7 from Salivary Gland Vectors of Malaria: Anopheles sundaicus." Jurnal ILMU DASAR 16, no. 1 (June 23, 2016): 37. http://dx.doi.org/10.19184/jid.v16i1.621.
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The isolation of Arthropod Odorant Binding, D7 protein, encoding genes from Anopheles sundaicus and An. maculatus mosquitos as the malaria vectors in Indonesia is necessary to recognize their characteristic. The isolated genes can be used to develop the Transmission Blocking Vaccine (TBV). This research aims to characterize the D7 protein encoding genes from An. sundaicus and An. maculatus through the synthesis of complementary DNA (cDNA) of D7 protein by using D7 protein primer that has been used for the other species of Anopheles. The mosquitos were taken from Dusun Parasputih, Bangsring, Wongsorejo, Banyuwangi, Jawa Timur. Isolation of the salivary gland was done by performing microdisection method and the isolation of the total RNA was done by performing High Pure RNA Isolation Kit (Roche-Germany). Synthesis of cDNA D7 encoding gene and its amplification were performed by using Maxime RT-PCR Premix Kit (iNtRon Biotechnology). The result of the total RNA and RT-PCR were run in agarose gel and visualized under the UV transiluminator. Based on the visualization, we found that the salivary gland total RNA of female An. sundaicus was 500-750 base pair (bp). The RT-PCR visualization showed a band sized below 100 bp and it was concluded not to be the size of the D7 protein encoding gene. An incompatibility of D7 primer from An. gambiae with cDNA template from An. sundaicus was suspected to be the reason of the gene isolation failure.Keywords: gene isolation, D7 protein, salivary gland, Anopheles sundaicus
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Bazant, Eva, Carol McPhillips-Tangum, Sumitra Devi Shrestha, Preetha G S, Ajay Khera, Laura Nic Lochlainn, Esmael Habtamu, Vivek I. Patel, Gladys Muhire, and Kristin N. Saarlas. "Promising practices for the collaborative planning of integrated health campaigns from a synthesis of case studies." BMJ Global Health 7, no. 12 (December 2022): e010321. http://dx.doi.org/10.1136/bmjgh-2022-010321.
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A combination of public health campaigns and routine primary healthcare services are used in many countries to maximise the number of people reached with interventions to prevent, control, eliminate or eradicate diseases. Health campaigns have historically been organised within vertical (disease-specific) programmes, which are often funded, planned and implemented independently from one another and from routinely offered primary healthcare services. Global health agencies have voiced support for enhancing campaign effectiveness, including campaign efficiency and equity, through collaboration among vertical programmes. However, limited guidance is available to country-level campaign planners and implementers about how to effectively integrate campaigns. Planning is critical to the implementation of effective health campaigns, including those related to neglected tropical diseases, malaria, vitamin A supplementation and vaccine-preventable diseases, including polio, measles and meningitis. However, promising approaches to planning integrated health campaigns have not been sufficiently documented. This manuscript highlights promising practices for the collaborative planning of integrated health campaigns that emerged from the experiences of eight project teams working in three WHO regions. Adoption of the promising practices described in this paper could lead to enhanced collaboration among campaign stakeholders, increased agreement about the need for and anticipated benefits of campaign integration, and enhanced understanding of effective planning of integrated health campaigns.
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Meerstein-Kessel, Lisette, Jeron Venhuizen, Daniel Garza, Nicholas I. Proellochs, Emma J. Vos, Joshua M. Obiero, Philip L. Felgner, et al. "Novel insights from the Plasmodium falciparum sporozoite-specific proteome by probabilistic integration of 26 studies." PLOS Computational Biology 17, no. 4 (April 30, 2021): e1008067. http://dx.doi.org/10.1371/journal.pcbi.1008067.
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Plasmodium species, the causative agent of malaria, have a complex life cycle involving two hosts. The sporozoite life stage is characterized by an extended phase in the mosquito salivary glands followed by free movement and rapid invasion of hepatocytes in the human host. This transmission stage has been the subject of many transcriptomics and proteomics studies and is also targeted by the most advanced malaria vaccine. We applied Bayesian data integration to determine which proteins are not only present in sporozoites but are also specific to that stage. Transcriptomic and proteomic Plasmodium data sets from 26 studies were weighted for how representative they are for sporozoites, based on a carefully assembled gold standard for Plasmodium falciparum (Pf) proteins known to be present or absent during the sporozoite life stage. Of 5418 Pf genes for which expression data were available at the RNA level or at the protein level, 975 were identified as enriched in sporozoites and 90 specific to them. We show that Pf sporozoites are enriched for proteins involved in type II fatty acid synthesis in the apicoplast and GPI anchor synthesis, but otherwise appear metabolically relatively inactive in the salivary glands of mosquitos. Newly annotated hypothetical sporozoite-specific and sporozoite-enriched proteins highlight sporozoite-specific functions. They include PF3D7_0104100 that we identified to be homologous to the prominin family, which in human has been related to a quiescent state of cancer cells. We document high levels of genetic variability for sporozoite proteins, specifically for sporozoite-specific proteins that elicit antibodies in the human host. Nevertheless, we can identify nine relatively well-conserved sporozoite proteins that elicit antibodies and that together can serve as markers for previous exposure. Our understanding of sporozoite biology benefits from identifying key pathways that are enriched during this life stage. This work can guide studies of molecular mechanisms underlying sporozoite biology and potential well-conserved targets for marker and drug development.
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Narita, Mitsuaki, Hitoshi Takegahara, Seiji Ono, and Hisaya Sato. "Usefulness of the Peptide Segment Separation Method for Asparagine-Rich Protein Syntheses. Synthesis of Malaria Vaccine Analogs Having the Repeated Unit of L-Asparaginyl-L-Alanyl-L-Asparaginyl-L-Prolyl." Bulletin of the Chemical Society of Japan 63, no. 2 (February 1990): 484–88. http://dx.doi.org/10.1246/bcsj.63.484.
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Kain, Kevin C. "Chemotherapy of Drug-Resistant Malaria." Canadian Journal of Infectious Diseases 7, no. 1 (1996): 25–33. http://dx.doi.org/10.1155/1996/139612.
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OBJECTIVE: To review the impact of drug-resistant malaria on current management of plasmodial infections.DATA SOURCES: A MEDLINE search of the English-language medical literature from 1985 to 1995; bibliographies of selected papers; international malaria advisory experts.DATA SYNTHESIS: Combinations of artemisinin derivatives and mefloquine or atovaquone plus proguanil appear to be the most active drug regimens against multidrug-resistant falciparum malaria from Southeast Asia. The optimal therapy for chloroquine-resistantPlasmodium vivaxis unknown, but recent data indicate that halofantrine or chloroquine plus high doses of primaquine are efficacious.CONCLUSIONS: The incidence of drug-resistant malaria continues to increase at a rate that exceeds new drug development. Ultimately the control of malaria will require more creative approaches than just the development of additional inhibitory drugs. These might include the identification of biochemical pathways unique to the parasite (such as drug efflux and heme polymerization), making it possible to design new classes of antimalarial agents that are selectively toxic to the parasite; methods to block parasite development in the mosquito vector; and multistage vaccines against asexual and sexual stages to block both the pathophysiology and the transmission of disease.
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Mahajan, Babita, Jay A. Berzofsky, Robert A. Boykins, Victoria Majam, Hong Zheng, Rana Chattopadhyay, Patricia de la Vega, et al. "Multiple Antigen Peptide Vaccines against Plasmodium falciparum Malaria." Infection and Immunity 78, no. 11 (September 7, 2010): 4613–24. http://dx.doi.org/10.1128/iai.00533-10.
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ABSTRACT The multiple antigen peptide (MAP) approach is an effective method to chemically synthesize and deliver multiple T-cell and B-cell epitopes as the constituents of a single immunogen. Here we report on the design, chemical synthesis, and immunogenicity of three Plasmodium falciparum MAP vaccines that incorporated antigenic epitopes from the sporozoite, liver, and blood stages of the life cycle. Antibody and cellular responses were determined in three inbred (C57BL/6, BALB/c, and A/J) strains, one congenic (HLA-A2 on the C57BL/6 background) strain, and one outbred strain (CD1) of mice. All three MAPs were immunogenic and induced both antibody and cellular responses, albeit in a somewhat genetically restricted manner. Antibodies against MAP-1, MAP-2, and MAP-3 had an antiparasite effect that was also dependent on the mouse major histocompatibility complex background. Anti-MAP-1 (CSP-based) antibodies blocked the invasion of HepG2 liver cells by P. falciparum sporozoites (highest, 95.16% in HLA-A2 C57BL/6; lowest, 11.21% in BALB/c). Furthermore, antibodies generated following immunizations with the MAP-2 (PfCSP, PfLSA-1, PfMSP-142, and PfMSP-3b) and MAP-3 (PfRAP-1, PfRAP-2, PfSERA, and PfMSP-142) vaccines were able to reduce the growth of blood stage parasites in erythrocyte cultures to various degrees. Thus, MAP-based vaccines remain a viable option to induce effective antibody and cellular responses. These results warrant further development and preclinical and clinical testing of the next generation of candidate MAP vaccines that are based on the conserved protective epitopes from Plasmodium antigens that are widely recognized by populations of divergent HLA types from around the world.
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Hunter, R. L., M. R. Kidd, M. R. Olsen, P. S. Patterson, and A. A. Lal. "Induction of long-lasting immunity to Plasmodium yoelii malaria with whole blood-stage antigens and copolymer adjuvants." Journal of Immunology 154, no. 4 (February 15, 1995): 1762–69. http://dx.doi.org/10.4049/jimmunol.154.4.1762.
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Abstract We previously reported that protection of mice from nonlethal Plasmodium yoelii malaria by immunization with whole killed blood-stage parasites was dependent on the adjuvant and that adjuvants influenced both the specificity and isotype of Ab. Additional studies with the most effective formulations were undertaken to better define the protective responses and 100% protection from lethal P. yoelii malaria was produced by three immunizations with Ag in copolymer P1004 and detoxified RaLPS as adjuvants and 83% protection was induced by a single immunization. The protection lasted for 9 mo and was associated with an anamnestic rise in Ab titer of the IgG2a isotype during the challenge infection. Passive immunization with Ab from animals that had been immunized and challenged transferred sterile immunity. Splenectomy reduced, but did not abolish, protection. These data suggest that the effective Ab is directed against labile epitopes on the surface of blood-stage parasites. The vaccines primed animals for production of such Ab, but its synthesis was efficiently induced only by challenge with live organisms.
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Pinheiro, Luan Ramalho, Giovanna Diniz Della Croce, Francielle Dutra Aguiar, Bruna de Oliveira Thomasi, Thaís Mirelli Rêgo Bezerra, Grasiele de Sousa Vieira Tavares, Eduardo Antônio Ferraz Coelho, Geraldo Célio Brandão, and Guilherme Rocha Pereira. "Synthesis of novel aminoquinolines with potential leishmanicidal and antimalarial biological activity / Síntese de novas aminoquinolinas com potencial actividade biológica leishmanicida e antimalárica." Brazilian Journal of Development 7, no. 12 (December 29, 2021): 118095–105. http://dx.doi.org/10.34117/bjdv7n12-527.
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Leishmaniasis is a disease transmitted by different parasite species of the genus Leishmania, while malaria, by protozoa of the genus Plasmodium sp. These diseases affect tropical and subtropical regions, where about half of the world's population live. However, leishmaniasis and malaria are considered neglected diseases because these regions are poor, and consequently have precarious essential sanitation networks. In response to the lack of vaccines and effective medical measures, some natural and synthetic medicines are used as forms of treatment, such as quinoline derivatives necessary to treat malaria. Even so, the parasites have shown resistance to forms of treatment, which makes needed the constant development of new drugs with potential against them. Quinoline derivatives, chloroquine analogues, have potential activity for the diseases of interest, while anilines are molecules used in nucleophilic reactions on different substrates. Therefore, the work consisted of exploring the synthesis between these two compounds through subsequent reactions involving the formation of intermediates that resulted in the products of interest. Twelve novel derivatives with potential leishmanicidal and antimalarial biological activity were synthesized. The molecules produced were purified and rightly characterized by several methods, such as mass spectrometry, infrared spectroscopy, and Nuclear Magnetic Resonance of Carbon (13C) and Hydrogen (1H). Also, were obtained the melting points of the synthesized molecules. Finally, all products were sent for biological tests against the parasites, getting highly effective results for the protozoa responsible for leishmaniasis.
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Meteke, Sarah, Marianne Stefopulos, Daina Als, Michelle F. Gaffey, Mahdis Kamali, Fahad J. Siddiqui, Mariella Munyuzangabo, et al. "Delivering infectious disease interventions to women and children in conflict settings: a systematic review." BMJ Global Health 5, Suppl 1 (April 2020): e001967. http://dx.doi.org/10.1136/bmjgh-2019-001967.
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BackgroundConflict has played a role in the large-scale deterioration of health systems in low-income and middle-income countries (LMICs) and increased risk of infections and outbreaks. This systematic review aimed to synthesise the literature on mechanisms of delivery for a range of infectious disease-related interventions provided to conflict-affected women, children and adolescents.MethodsWe searched Medline, Embase, CINAHL and PsychINFO databases for literature published in English from January 1990 to March 2018. Eligible publications reported on conflict-affected neonates, children, adolescents or women in LMICs who received an infectious disease intervention. We extracted and synthesised information on delivery characteristics, including delivery site and personnel involved, as well as barriers and facilitators, and we tabulated reported intervention coverage and effectiveness data.ResultsA majority of the 194 eligible publications reported on intervention delivery in sub-Saharan Africa. Vaccines for measles and polio were the most commonly reported interventions, followed by malaria treatment. Over two-thirds of reported interventions were delivered in camp settings for displaced families. The use of clinics as a delivery site was reported across all intervention types, but outreach and community-based delivery were also reported for many interventions. Key barriers to service delivery included restricted access to target populations; conversely, adopting social mobilisation strategies and collaborating with community figures were reported as facilitating intervention delivery. Few publications reported on intervention coverage, mostly reporting variable coverage for vaccines, and fewer reported on intervention effectiveness, mostly for malaria treatment regimens.ConclusionsDespite an increased focus on health outcomes in humanitarian crises, our review highlights important gaps in the literature on intervention delivery among specific subpopulations and geographies. This indicates a need for more rigorous research and reporting on effective strategies for delivering infectious disease interventions in different conflict contexts.PROSPERO registration numberCRD42019125221.
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SOEIRO, M. N. C., K. WERBOVETZ, D. W. BOYKIN, W. D. WILSON, M. Z. WANG, and A. HEMPHILL. "Novel amidines and analogues as promising agents against intracellular parasites: a systematic review." Parasitology 140, no. 8 (April 8, 2013): 929–51. http://dx.doi.org/10.1017/s0031182013000292.
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SUMMARYParasitic protozoa comprise diverse aetiological agents responsible for important diseases in humans and animals including sleeping sickness, Chagas disease, leishmaniasis, malaria, toxoplasmosis and others. They are major causes of mortality and morbidity in tropical and subtropical countries, and are also responsible for important economic losses. However, up to now, for most of these parasitic diseases, effective vaccines are lacking and the approved chemotherapeutic compounds present high toxicity, increasing resistance, limited efficacy and require long periods of treatment. Many of these parasitic illnesses predominantly affect low-income populations of developing countries for which new pharmaceutical alternatives are urgently needed. Thus, very low research funding is available. Amidine-containing compounds such as pentamidine are DNA minor groove binders with a broad spectrum of activities against human and veterinary pathogens. Due to their promising microbicidal activity but their rather poor bioavailability and high toxicity, many analogues and derivatives, including pro-drugs, have been synthesized and screened in vitro and in vivo in order to improve their selectivity and pharmacological properties. This review summarizes the knowledge on amidines and analogues with respect to their synthesis, pharmacological profile, mechanistic and biological effects upon a range of intracellular protozoan parasites. The bulk of these data may contribute to the future design and structure optimization of new aromatic dicationic compounds as novel antiparasitic drug candidates.
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Kaur, Jasweer, and Rachna Hora. "‘2TM proteins’: an antigenically diverse superfamily with variable functions and export pathways." PeerJ 6 (May 11, 2018): e4757. http://dx.doi.org/10.7717/peerj.4757.
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Malaria is a disease that affects millions of people annually. An intracellular habitat and lack of protein synthesizing machinery in erythrocytes pose numerous difficulties for survival of the human pathogenPlasmodium falciparum. The parasite refurbishes the infected red blood cell (iRBC) by synthesis and export of several proteins in an attempt to suffice its metabolic needs and evade the host immune response. Immune evasion is largely mediated by surface display of highly polymorphic protein families known as variable surface antigens. These include the two trans-membrane (2TM) superfamily constituted by multicopy repetitive interspersed family (RIFINs), subtelomeric variable open reading frame (STEVORs) andPlasmodium falciparumMaurer’s cleft two trans-membrane proteins present only inP. falciparumand some simian infectingPlasmodiumspecies. Their hypervariable region flanked by 2TM domains exposed on the iRBC surface is believed to generate antigenic diversity. Though historically named “2TM superfamily,” several A-type RIFINs and some STEVORs assume one trans-membrane topology. RIFINs and STEVORs share varied functions in different parasite life cycle stages like rosetting, alteration of iRBC rigidity and immune evasion. Additionally, a member of the STEVOR family has been implicated in merozoite invasion. Differential expression of these families in laboratory strains and clinical isolates propose them to be important for host cell survival and defense. The role of RIFINs in modulation of host immune response and presence of protective antibodies against these surface exposed molecules in patient sera highlights them as attractive targets of antimalarial therapies and vaccines. 2TM proteins arePlasmodiumexport elements positive, and several of these are exported to the infected erythrocyte surface after exiting through the classical secretory pathway within parasites. Cleaved and modified proteins are trafficked after packaging in vesicles to reach Maurer’s clefts, while information regarding delivery to the iRBC surface is sparse. Expression and export timing of the RIFIN andPlasmodium falciparumerythrocyte membrane protein1 families correspond to each other. Here, we have compiled and comprehended detailed information regarding orthologues, domain architecture, surface topology, functions and trafficking of members of the “2TM superfamily.” Considering the large repertoire of proteins included in the 2TM superfamily and recent advances defining their function in malaria biology, a surge in research carried out on this important protein superfamily is likely.
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Shibeshi, Workineh, Wilhelmina Bagchus, Özkan Yalkinoglu, Aliona Tappert, Ephrem Engidawork, and Claude Oeuvray. "Reproducibility of malaria sporozoite challenge model in humans for evaluating efficacy of vaccines and drugs: a systematic review." BMC Infectious Diseases 21, no. 1 (December 2021). http://dx.doi.org/10.1186/s12879-021-06953-4.
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Abstract Background The development of novel malaria vaccines and antimalarial drugs is limited partly by emerging challenges to conduct field trials in malaria endemic areas, including unknown effects of existing immunity and a reported fall in malaria incidence. As a result, Controlled Human Malaria Infection (CHMI) has become an important approach for accelerated development of malarial vaccines and drugs. We conducted a systematic review of the literature to establish aggregate evidence on the reproducibility of a malaria sporozoite challenge model. Methods A systematic review of research articles published between 1990 and 2018 on efficacy testing of malaria vaccines and drugs using sporozoite challenge and sporozoite infectivity studies was conducted using Pubmed, Scopus, Embase and Cochrane Library, ClinicalTrials.gov and Trialtrove. The inclusion criteria were randomized and non-randomized, controlled or open-label trials using P. falciparum or P. vivax sporozoite challenges. The data were extracted from articles using standardized data extraction forms and descriptive analysis was performed for evidence synthesis. The endpoints considered were infectivity, prepatent period, parasitemia and safety of sporozoite challenge. Results Seventy CHMI trials conducted with a total of 2329 adult healthy volunteers were used for analysis. CHMI was induced by bites of mosquitoes infected with P. falciparum or P. vivax in 52 trials and by direct venous inoculation of P. falciparum sporozoites (PfSPZ challenge) in 18 trials. Inoculation with P. falciparum-infected mosquitoes produced 100% infectivity in 40 studies and the mean/median prepatent period assessed by thick blood smear (TBS) microscopy was ≤ 12 days in 24 studies. On the other hand, out of 12 infectivity studies conducted using PfSPZ challenge, 100% infection rate was reproduced in 9 studies with a mean or median prepatent period of 11 to 15.3 days as assessed by TBS and 6.8 to 12.6 days by PCR. The safety profile of P. falciparum and P.vivax CHMI was characterized by consistent features of malaria infection. Conclusion There is ample evidence on consistency of P. falciparum CHMI models in terms of infectivity and safety endpoints, which supports applicability of CHMI in vaccine and drug development. PfSPZ challenge appears more feasible for African trials based on current evidence of safety and efficacy.
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"Sources of Potential Fungi Generated Biogenic Nanoparticles for the Control of Diseases Transmitting Mosquitoes: A Review." Letters in Applied NanoBioScience 11, no. 2 (September 5, 2021): 3523–36. http://dx.doi.org/10.33263/lianbs112.35233536.
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Vector mosquitoes are diseases transmitting malaria, filarial, dengue, and Japanese encephalitis are an enormous burden to public people worldwide. There is no proper vaccine for those diseases; even though malaria is significant, challenges are still waiting for successful management. Recently, fungi and fungi-derived products control mosquito larvae, pupae, and adults better than compared to plants or other microorganisms. The using fungi such as Aspergillus sp., Beauveria bassiana, Metarhizium anisopliae, Verticillium lecanii are more virulent for controlling mosquito vectors, Aedes aegypti, Anopheles stephensi, Culex quinquefasciatus. The synthesis of silver, gold, zinc, and copper nanoparticles from those fungi has been getting good biological sources for significant reduction of mosquito larval and pupal populations. Fungal-based nanoparticles are highly effective and biorational insecticide for the control of vector populations. In this review, we discussed various sources of fungi that can be synthesized from different nanoparticles to control disease-transmitting mosquito vectors.
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Barra, Angélica Luana C., Najeeb Ullah, Luana G. Morão, Carsten Wrenger, Christian Betzel, and Alessandro S. Nascimento. "Structural Dynamics and Perspectives of Vitamin B6 Biosynthesis Enzymes in Plasmodium: Advances and Open Questions." Frontiers in Cellular and Infection Microbiology 11 (July 13, 2021). http://dx.doi.org/10.3389/fcimb.2021.688380.
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Malaria is still today one of the most concerning diseases, with 219 million infections in 2019, most of them in Sub-Saharan Africa and Latin America, causing approx. 409,000 deaths per year. Despite the tremendous advances in malaria treatment and prevention, there is still no vaccine for this disease yet available and the increasing parasite resistance to already existing drugs is becoming an alarming issue globally. In this context, several potential targets for the development of new drug candidates have been proposed and, among those, the de novo biosynthesis pathway for the B6 vitamin was identified to be a promising candidate. The reason behind its significance is the absence of the pathway in humans and its essential presence in the metabolism of major pathogenic organisms. The pathway consists of two enzymes i.e. Pdx1 (PLP synthase domain) and Pdx2 (glutaminase domain), the last constituting a transient and dynamic complex with Pdx1 as the prime player and harboring the catalytic center. In this review, we discuss the structural biology of Pdx1 and Pdx2, together with and the understanding of the PLP biosynthesis provided by the crystallographic data. We also highlight the existing evidence of the effect of PLP synthesis inhibition on parasite proliferation. The existing data provide a flourishing environment for the structure-based design and optimization of new substrate analogs that could serve as inhibitors or even suicide inhibitors.
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Pérez-Moreno, Guiomar, Paula Sánchez-Carrasco, Luis Miguel Ruiz-Pérez, Nils Gunnar Johansson, Sylke Müller, Beatriz Baragaña, Shahienaz Emma Hampton, et al. "Validation of Plasmodium falciparum dUTPase as the target of 5′-tritylated deoxyuridine analogues with anti-malarial activity." Malaria Journal 18, no. 1 (December 2019). http://dx.doi.org/10.1186/s12936-019-3025-2.
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Abstract Background Malaria remains as a major global problem, being one of the infectious diseases that engender highest mortality across the world. Due to the appearance of resistance and the lack of an effective vaccine, the search of novel anti-malarials is required. Deoxyuridine 5′-triphosphate nucleotido-hydrolase (dUTPase) is responsible for the hydrolysis of dUTP to dUMP within the parasite and has been proposed as an essential step in pyrimidine metabolism by providing dUMP for thymidylate biosynthesis. In this work, efforts to validate dUTPase as a drug target in Plasmodium falciparum are reported. Methods To investigate the role of PfdUTPase in cell survival different strategies to generate knockout mutants were used. For validation of PfdUTPase as the intracellular target of four inhibitors of the enzyme, mutants overexpressing PfdUTPase and HsdUTPase were created and the IC50 for each cell line with each compound was determined. The effect of these compounds on dUTP and dTTP levels from P. falciparum was measured using a DNA polymerase assay. Detailed localization studies by indirect immunofluorescence microscopy and live cell imaging were also performed using a cell line overexpressing a Pfdut-GFP fusion protein. Results Different attempts of disruption of the dut gene of P. falciparum were unsuccessful while a 3′ replacement construct could recombine correctly in the locus suggesting that the enzyme is essential. The four 5′-tritylated deoxyuridine analogues described are potent inhibitors of the P. falciparum dUTPase and exhibit antiplasmodial activity. Overexpression of the Plasmodium and human enzymes conferred resistance against selective compounds, providing chemical validation of the target and confirming that indeed dUTPase inhibition is involved in anti-malarial activity. In addition, incubation with these inhibitors was associated with a depletion of the dTTP pool corroborating the central role of dUTPase in dTTP synthesis. PfdUTPase is mainly localized in the cytosol. Conclusion These results strongly confirm the pivotal and essential role of dUTPase in pyrimidine biosynthesis of P. falciparum intraerythrocytic stages.
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Huffstetler, Hanna E., Shashika Bandara, Ipchita Bharali, Kaci Kennedy McDade, Wenhui Mao, Felicia Guo, Jiaqi Zhang, et al. "The Impacts of Donor Transitions on Health Systems in Middle-Income Countries: A Scoping Review." Health Policy and Planning, July 29, 2022. http://dx.doi.org/10.1093/heapol/czac063.
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Abstract Introduction As countries graduate from low-income to middle-income status, many face losses in development assistance for health, and must “transition” to greater domestic funding of their health response. If improperly managed, donor transitions in middle-income countries (MICs) could present significant challenges to global health progress. No prior knowledge synthesis has comprehensively surveyed how donor transitions can affect health systems in MICs. Methods We conducted a scoping review using a structured search strategy across five academic databases and 37 global health donor and think tank websites for literature published between January 1990 and October 2018. We used the WHO health system “building blocks” framework to thematically synthesize and structure the analysis. Results Following independent screening, 89 publications out of 11,236 were included for data extraction and synthesis. Most of this evidence examines transitions related to HIV/AIDS (n=45, 50%) and immunization programs (n=14, 16%), with a focus on donors such as the Global Fund to Fight AIDS, Tuberculosis and Malaria (n=26, 29%), and Gavi, the Vaccine Alliance (n=15, 17%). Donor transitions are influenced by the actions of both donors and country governments, with impacts on every component of the health system. Successful transition experiences show that leadership, planning, and pre-transition investments in a country’s financial, technical, and logistical capacity are vital to ensuring smooth transition. In the absence of such measures, shortages in financial resources, medical product and supply stockouts, service disruptions, and shortages in human resources were common, with resulting implications not only for program continuation, but also for population health. Conclusion Donor transitions can affect different components of the health system in varying and interconnected ways. More rigorous evaluation of how donor transitions can affect health systems in MICs will create an improved understanding of the risks and opportunities posed by donor exits.
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Nayak, Akshaykumar, Himani Saxena, Chandramohan Bathula, Tarkeshwar Kumar, Souvik Bhattacharjee, Subhabrata Sen, and Ashish Gupta. "Diversity-oriented synthesis derived indole based spiro and fused small molecules kills artemisinin-resistant Plasmodium falciparum." Malaria Journal 20, no. 1 (February 17, 2021). http://dx.doi.org/10.1186/s12936-021-03632-2.
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Abstract Background Despite numerous efforts to eradicate the disease, malaria continues to remain one of the most dangerous infectious diseases plaguing the world. In the absence of any effective vaccines and with emerging drug resistance in the parasite against the majority of anti-malarial drugs, the search for new drugs is urgently needed for effective malaria treatment. Methods The goal of the present study was to examine the compound library, based on indoles generated through diversity-oriented synthesis belonging to four different architecture, i.e., 1-aryltetrahydro/dihydro-β-carbolines and piperidine/pyrrolidine-fused indole derivatives, for their in vitro anti-plasmodial activity. Trifluoroacetic acid catalyzed transformation involving tryptamine and various aldehydes/ketones provided the library. Results Among all the compounds screened, 1-aryltetrahydro-β-carbolines 2 and 3 displayed significant anti-plasmodial activity against both the artemisinin-sensitive and artemisinin-resistant strain of Plasmodium falciparum. It was observed that these compounds inhibited the overall parasite growth in intra-erythrocytic developmental cycle (IDC) via reactive oxygen species-mediated parasitic death and thus could be potential anti-malarial compounds. Conclusion Overall the compounds 2 and 3 identified in this study shows promising anti-plasmodial activity that can kill both artemisinin-sensitive and artemisinin-resistant strains of P. falciparum.
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"The conformational restriction of synthetic peptides, including a malaria peptide, for use as immunogens." Philosophical Transactions of the Royal Society of London. B, Biological Sciences 323, no. 1217 (June 12, 1989): 565–72. http://dx.doi.org/10.1098/rstb.1989.0036.
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A new strategy is advanced for the conformational restriction of peptidyl immunogens. Our approach is to replace putative amide-amide hydrogen bonds with covalent hydrogen-bond mimics. Because on average every other amino acid in a protein engages in this bond, the syntheses of diversely shaped peptides can be contemplated. Synthetic methods for introducing a potential hydrogen-bond mimic into a peptide with α-helical potential is reported and the structural consequences are discussed. The replacement of the hydrogen bond with a chemical link will modify as well as shape the peptide. To explore the consequences of these changes, a potential synthetic vaccine for malaria, the repeating tetrapeptide Asn-Pro-Asn-Ala, was conformationally restricted. Antibodies to the shaped malarial peptide showed a strong cross reaction with Plasmodium falciparum sporozoites.
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"The Leeuwenhoek Lecture, 1993. Peptide vaccines: dream or reality?" Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 344, no. 1308 (April 29, 1994): 213–19. http://dx.doi.org/10.1098/rstb.1994.0062.
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Small fragments of micro-organisms which elicit protective immune responses have now been identified for several disease-causing agents. This major advance has made it possible to envisage the chemical synthesis of vaccines which could replace those in current use and may also furnish products which cannot be made by traditional methods. In my lecture I will illustrate the principles involved by describing the advances made with synthetic vaccines for foot-and-mouth disease, hepatitis B and malaria.
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Zhang, Yan-hui, Xin-zhuan Su, Jian Li, Jia-jian Shi, and Li-hua Xie. "Multicohort transcriptome analysis of whole blood identifies robust human response signatures in Plasmodium falciparum infections." Malaria Journal 21, no. 1 (November 15, 2022). http://dx.doi.org/10.1186/s12936-022-04374-5.
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Abstract Background To understand how Plasmodium falciparum malaria is controlled, it is essential to elucidate the transcriptomic responses of the human host in naturally-exposed populations. Various individual studies of the human transcriptomic responses to naturally transmitted P. falciparum infections have been reported with varying results. Multicohort gene expression analysis by aggregating data from diverse populations into a single analysis will increase the reproducibility and reliability of the results. Methods In this study, discovery cohorts GSE1124-GPL96, GSE34404, GSE117613, and validation cohort GSE35858 were obtained from the Gene Expression Omnibus. A meta-analysis using data from the multicohort studies was performed to identify the differentially expressed genes (DEGs) between malaria-infected and noninfected individuals using the MetaIntegrator R package. Subsequently, the protein–protein interaction (PPI) networks of the DEGs were constructed using Cytoscape software. Significant modules were selected, and the hub genes were identified using the CytoHubba and MCODE plug-ins. Multicohort WGCNA was conducted to find a correlation between modules and malaria infection. Furthermore, the immune cell profile of the peripheral blood in different groups was identified using ssGSEA. Results These analyses reveal that neutrophil activation, neutrophil-mediated immunity, and neutrophil degranulation are involved in the human response to natural malaria infection. However, neutrophil cell enrichment and activation were not significantly different between mild malaria and severe malaria groups. Malaria infection also downregulates host genes in ribosome synthesis and protein translation and upregulates host cell division-related genes. Furthermore, immune cell profiling analysis shows that activated dendritic cells and type 2 T helper cells are upregulated, while activated B cells, immature B cells, and monocytes are downregulated in the malaria-infected patients relative to the noninfected individuals. Significantly higher enrichment of activated dendritic cell-related genes and significantly lower enrichment of monocyte-related genes are also observed in the peripheral blood of the severe malaria group than in the mild malaria group. Conclusion These results reveal important molecular signatures of host responses to malaria infections, providing some bases for developing malaria control strategies and protective vaccines.
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LeBras, Marlys H., and Arden R. Barry. "Influenza Vaccination for Secondary Prevention of Cardiovascular Events: A Systematic Review." Canadian Journal of Hospital Pharmacy 70, no. 1 (March 1, 2017). http://dx.doi.org/10.4212/cjhp.v70i1.1626.
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<p><strong>ABSTRACT</strong></p><p><strong>Background:</strong> Influenza is a common respiratory infection that may cause complications, including cardiovascular events. Influenza illness has been shown to double the risk of myocardial infarction, with the highest risk among patients with established cardiovascular disease. Vaccination against influenza has been associated with reductions in myocardial infarction, cerebrovascular disease, and death.</p><p><strong>Objective:</strong> To evaluate the evidence for influenza vaccination as a strategy to reduce cardiovascular events specifically in patients with established cardiovascular disease.</p><p><strong>Data Sources and Study Selection:</strong> MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched with the terms “influenza vaccine” and “cardiovascular disease”. Included in this review were randomized controlled trials (RCTs), nonrandomized studies, and meta-analyses that compared influenza vaccination against control in patients with established cardiovascular disease and that reported clinically meaningful cardiovascular outcomes (defined as cardiovascular death, myocardial infarction, and stroke).</p><p><strong>Data Extraction and Synthesis:</strong> The search yielded 10 studies (3 nonrandomized studies, 5 RCTs, and 2 meta-analyses). The nonrandomized studies and the RCTs had inconsistent results with respect to cardio - vascular death and adverse cardiovascular events. The 2 meta-analyses, which included the same 4 RCTs involving patients with established cardiovascular disease, showed that the influenza vaccine reduced cardiovascu lar death by about 50% relative to control. Vaccination also reduced major cardiovascular events by about 43%; the reduction was greater (54%) in the subgroup of patients with recent (≤ 1 year) acute coronary syndrome. However, these data are potentially confounded by small sample sizes, low event rates, and variable outcome reporting. There was also high clinical heterogeneity among the studies, which may not reflect contemporary practice.</p><p><strong>Conclusions:</strong> Given the limitations of these data, it is unclear whether the cardiovascular benefit with influenza vaccination in patients with cardiovascular disease is a true effect. Nevertheless, because of the potential benefit and the low risk of adverse events, the annual influenza vaccine should be recommended for all patients with established cardiovascular disease.</p><p><strong>RÉSUMÉ</strong></p><p><strong>Contexte :</strong> La grippe est une infection courante des voies respiratoires qui peut causer des complications, notamment des événements cardiovasculaires. On a montré que la grippe double les risques d’infarctus du myocarde. De plus, les patients atteints d’une maladie cardiovasculaire sont les plus menacés. La vaccination contre la grippe a été associée à une réduction des cas d’infarctus du myocarde, de maladie cérébrovasculaire et de décès.</p><p><strong>Objectif :</strong> Évaluer les données probantes montrant que la vaccination contre la grippe permet de réduire le nombre d’événements cardiovasculaires chez les patients déjà atteints d’une maladie cardiovasculaire.</p><p><strong>Sources des données et sélection des études :</strong> Les bases de données MEDLINE et Embase et le Registre central Cochrane des essais aléatoires ont été interrogés en utilisant les termes « vaccin antigrippal » et « maladie cardiovasculaire ». Les études retenues pour la présente revue de la littérature devaient être des essais cliniques à répartition aléatoire, des essais cliniques non aléatoires ou des méta-analyses. De plus, elles devaient comparer les résultats de patients vaccinés contre la grippe et atteints d’une maladie cardiaque à ceux d’un groupe témoin qui étaient aussi atteints d’une maladie cardiaque. Enfin, elles devaient signaler des résultats cardiovasculaires cliniquement significatifs (définis comme un décès d’origine cardiovasculaire, un infarctus du myocarde ou un accident vasculaire cérébral).</p><p><strong>Extraction et synthèse des données :</strong> Dix études répondaient aux critères de recherche (trois essais cliniques non aléatoires, cinq essais cliniques à répartition aléatoire et deux méta-analyses). Les essais cliniques non aléatoires et les essais cliniques à répartition aléatoire présentaient des résultats variables en ce qui touche aux décès d’origine cardiovasculaire et aux événements cardiovasculaires indésirables. Les deux méta-analyses, qui avaient en commun quatre essais cliniques à répartition aléatoire concernant des patients atteints d’une maladie cardiovasculaire, montraient que le vaccin contre la grippe permettait de réduire le nombre de décès d’origine cardiovasculaire d’environ 50 % comparativement au groupe témoin. La vaccination a aussi réduit le nombre d’événements cardiovasculaires graves d’environ 43 %; le pourcentage était plus important (54 %) dans le sous-groupe de patients ayant récemment (à l’intérieur d’un an) souffert d’un syndrome coronarien aigu. Cependant, ces résultats sont potentiellement faussés par la petite taille des échantillons, les faibles taux d’événements et la variabilité avec laquelle on signale les résultats. Il y avait aussi une forte hétérogénéité clinique entre les études, ce qui pourrait ne pas être représentatif de la pratique actuelle.</p><p><strong>Conclusions</strong> : En raison des limites de ces données, on ignore si le vaccin antigrippal offre réellement des effets cardiovasculaires bénéfiques pour les patients atteints d’une maladie cardiovasculaire. Néanmoins, compte tenu des avantages potentiels et du faible risque d’événements indésirables, le vaccin annuel contre la grippe doit être recommandé pour tous les patients atteints d’une maladie cardiovasculaire.</p>