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Epitope Discovery and Synthetic Vaccine Design

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455225 Year: Pages: 284 DOI: 10.3389/978-2-88945-522-5 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2019-01-23 14:53:42
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Since variolation, conventional approaches to vaccine development are based on live-attenuated, inactivated or purified pathogen-derived components. However, effective vaccines against global health threats such as HIV, parasite infections and tumors are difficult to achieve. On the other hand, synthetic vaccines based on immunogenic epitopes offer advantages over traditional vaccines since they are chemically defined antigens free from deleterious effects. Additionally, in contrast to live-attenuated vaccines, they do not revert to virulence in immunocompromised subjects, and different from genetic vaccines, they do not involve ethical questions. Traditional vaccines contain PAMPs and induce strong immune responses, while recombinant vaccines are less potent. In spite of the immunogenic weakness previously attributed to epitope-based vaccines a synthetic vaccine containing a 17 amino acid-epitope of the Pseudomonas aeruginosa Type IV pilus exceeded the protective potential of its cognate protein composed of 115 amino acids. Therefore, the efficacy yield of a synthetic vaccine can be potentiated by using the proper combination of target epitopes. Recent advances in adjuvant development, immunogen platforms for DNA vaccines and viral vectors also contributed to optimize immunogenicity. Another constraint to the use of epitope vaccines was their restriction to some MHC or HLA phenotypes. However, epitopes containing 20 or less amino acids of Plasmodium falciparum and Leishmania donovani bind to multiple HLA-DR and MHC receptors. Thus synthetic epitope vaccines may better meet the requirements of the regulatory agencies since they have lower costs and are easier to produce. The classical experimental approach for the development of an epitope-based vaccine involves the use of recombinant domains or overlapping 15-mer peptides spanning the full length of the target antigen, and the analysis of the induced antibody and/or T cell immune responses in vitro or in vivo. On the other hand, in silico tools can select peptides that are more likely to contain epitopes, reducing the number of sequence candidates. T cell epitope prediction dates back to 1980s, when the first algorithm was developed based on the identification of amphipathic helical regions on protein antigens. Since then, new methods based on MHC peptide-binding motifs or MHC-binding properties have been developed. The recent reverse vaccinology concept uses high-throughput genome sequencing and bioinformatics tools to identify potential targets of immune responses. The feasibility of this approach was shown for the first time in the design of a vaccine against Neisseria meningitides that is now in phase III clinical trials. In addition, different computational tools allow the determination of crucial gene(s) through comparative analyses between different pathogenic strains Alternatively, carbohydrates have been considered as key targets in developing safe and effective vaccines to combat cancer, bacterial and viral infections. Tumor associated carbohydrate antigens can be coupled covalently to protein carriers to target MHC receptors and improve immunogenicity and have reached already pre-clinical and clinical studies. In light of the recent availability of genomic tools, we believe that in the near future an increasing number of vaccine candidates, composed of defined epitopes, will be available for synthetic vaccines showing improved protection.

Protective Immune Response to Dengue Virus Infection and Vaccines: perspectives from the field to the bench

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195114 Year: Pages: 97 DOI: 10.3389/978-2-88919-511-4 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2015-12-03 13:02:24
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Dengue is the most important mosquito-transmitted viral disease in humans. Half of the world population is at risk of infection, mostly in tropical and sub-tropical areas. The World Health Organization (WHO) estimates that 50 to 100 million infections occur yearly, with 50,000 to 100,000 deaths related to dengue, mainly in children. Recent estimates show higher numbers, up to three times more, with 390 million estimated dengue infections per year, among which 96 million apparent infections (Bhatt et al. 2013). Initially localized to South-East Asia, dengue virus (DENV) started its spread in Latin America in the 80s. Little is known about DENV spread in Africa, but multiple seroprevalence surveys over several years are now clearly showing endemic areas in East and West Africa (Brady et al. 2013). Finally, due to global warming and intense traveling there is a risk of global spread towards more temperate regions, and both US Key islands (FL) and southern Europe recently faced DENV outbreaks. There are currently no specific treatments or vaccines available. Even though several dengue vaccines are in the pipeline, clear correlates of protection are still lacking. The recent failure of the live-attenuated Sanofi vaccine Phase 2b trial (Sabchareon et al. 2013) and the lack of correlation between clinical protection and in vitro neutralization assays, clearly underlines the necessity to better understand the role of the different components of the immune system in protection against dengue virus infection and the requirement for the development of additional and/or improved predictive assays. The aim of this research topic is to provide novel data, opinions and literature reviews on the best immune correlates of protection and recent advances in the immune response to DENV infection that can allow rapid progress of dengue vaccines. Authors can choose to submit original research papers, reviews or opinions on pre-clinical or clinical observations that will help unify the field, with perspectives from epidemiology, virology, immunology and vaccine developers. This research topic will discuss different aspects of the protective immune response to DENV that can influence vaccine development. It will include a review of epidemiological data generated in the field, which will address spatio-temporal diversity of DENV epidemics, the importance of cross-reactive protection and of the time-interval between infections as a predictor of disease. It will further include a review of the role of both the innate and adaptive immunity in DENV infection control, and discuss the usefulness of new improved animal models in dissecting the role of each immunological compartment, which will help define new correlate of immune protection. New data concerning the DENV structure and anti-dengue antibody structure will address the necessity of improved neutralization assays. The ultimate test to prove vaccine efficacy and study immune correlates of protection in humans before large trials will open up the discussion on human DENV challenges using controlled attenuated viral strains. Finally, the role of vaccines, administered in flavi-immune populations, in the modification of future epidemics will also be approached and will include novel studies on mosquitoes infection thresholds.

Endoplasmic Reticulcum and Its Role in Tumor Immunity

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197866 Year: Pages: 101 DOI: 10.3389/978-2-88919-786-6 Language: English
Publisher: Frontiers Media SA
Subject: Oncology --- Medicine (General)
Added to DOAB on : 2016-04-07 11:22:02
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The endoplasmic reticulum (ER) is an organelle crucial to many cellular functions and processes, including the mounting of T-cell immune responses. Indeed, the ER has a well-established central role in anti-tumor immunity. Perhaps best characterized is the role of the ER in the processing of antigen peptides and the subsequent peptide assembly into MHC class I and II molecules. Such MHC/tumor-derived peptide complexes are pivotal for the correct recognition of altered self or viral peptides and the subsequent clonal expansion of tumor-reactive T-cells. In line with the role of the ER in immunity, tumor-associated mutations in ER proteins, as well as ER protein content and localization can have both deleterious and advantageous effects on anti-tumor immune responses. For instance, loss of function of ER-aminopeptidases, that trim peptides to size for MHC, alter the MHC class I - peptide repertoire thereby critically and negatively affecting T-cell recognition. On the other hand, altered localization of ER proteins can have immune-promoting effects. Specifically, translocation of certain ER proteins to the cell surface has been shown to promote anti-tumor T-cell immunity by directing uptake of apoptotic tumor cells to professional antigen presenting cells, thereby facilitating anti-tumor T-cell immunity. These selected examples highlight a diverse and multi-faceted role of the ER in anti-tumor immunity. Molecular biological insights from the past decade have uncovered that ER components may affect tumor immunity and have invoked a variety of follow-up questions. For instance, how and why are ER proteins over-expressed in tumors? How do nucleotide and somatic mutations in ER chaperones/processing machinery affect the MHC/peptide complex and tumor cell immunogenicity? How do ER-proteins translocate to the cell surface? What if any is the potential role of extracellular ER protein in tumor immunotherapy/vaccines, and can they be delivered to the tumor cell surface by photodynamic therapy, anthracyclines or by other means? In this special research topics issue, we present basic and clinical research reports covering many aspects of ER proteins in cancer recognition by the immune system, therapy and drug development. We also present new insights into ER stress, signalling and homeostasis in immunogenic cell death in cancer, the effect of parasitic ER proteins on tumour growth, ER protein regulation of angiogenesis. A comprehensive series of articles highlight our understanding of an expanding avenue of tumour immunology and therapeutic development, which exploit a collection of proteins within the ER that are not obvious candidates for immunity against tumors.

Porcine Viruses

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ISBN: 9783038424727 9783038424734 Year: Pages: X, 320
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology
Added to DOAB on : 2017-08-31 10:53:55
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Pig production is the fastest growing segment of the global livestock sector. Intensification of pig production has resulted in significant changes to traditional pig husbandry practices. Combined with urbanization and ease of travel and transport, these changes have led to an environment conducive to increased emergence and spread of viral diseases. The past decade alone has seen the global emergence and re-emergence of porcine viruses with devastating consequences: For example, in 2006, highly pathogenic porcine reproductive and respiratory syndrome viruses (PRRSV) spread rapidly across Southeast Asia killing millions of animals; since its introduction into the Caucasus in 2007, the African swine fever virus has steadily spread to Eastern Europe; and in 2013-14, over 8 million pigs died when virulent porcine epidemic diarrhea virus (PEDV) swept North America. In this special issue we will explore our understanding of porcine viruses and how this may be exploited to improve the control of these pathogens of economic and agricultural significance.

Interaction of Nanomaterials with the Immune System: Role in Nanosafety and Nanomedicinenanomedicine

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453870 Year: Pages: 177 DOI: 10.3389/978-2-88945-387-0 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2018-11-16 17:17:57
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The immune system has the double role of maintaining tissue integrity and homeostasis and of protecting the organism from possible dangers, from invading pathogens to environmentally-borne dangerous chemicals. New chemicals recognisable by the immune system are engineered nanomaterials/ nanoparticles, new agents in our environment that are becoming common due to their presence in many products, from constructions and building material (e.g., solar cells, pigments and paints, tiles and masonry materials) to daily products (e.g., food packaging, cosmetics, and cigarettes). Human beings can be accidentally exposed to engineered nanomaterials when these are released from products containing them or during production in workplaces. Furthermore, intentional exposure occurs in medicine, as engineered nanoparticles are used as tools for improving delivery of drugs and vaccines, vaccine adjuvants and contrast agents in therapeutic, preventive and diagnostic strategies. Nanoparticles that come in contact with the immune system after unintentional exposure need to be eliminated from the organism as they represent a potential threat. In this case, however, due to their peculiar characteristics of size, shape, surface charge and persistence, nanoparticles may elicit undesirable reactions and have detrimental effects on the immune system, such as cytotoxicity, inflammation, anaphylaxis, immunosuppression. Conversely, nanomedicines need to escape immune recognition/elimination and must persist in the organism long enough for reaching their target and exerting their beneficial effects. Immune cells and molecules at the body surface (airway and digestive mucosae, skin) are the first that come in contact with nanomaterials upon accidental exposure, while immune effectors in blood are those that more easily come in contact with nanomedical products. Thus, evaluating the interaction of the immune system with nanoparticles/nanomaterials is a topic of key importance both in nanotoxicology and in nanomedicine. Immuno-nanosafety studies consider both accidental exposure to nanoparticles, which may occur by skin contact, ingestion or inhalation (at doses and with a frequency that are not known), and medical exposure, which takes place with a defined administration schedule (route, dose, frequency). Many studies focus on the interaction between the immune system and nanoparticles that, for medical purposes, have been specifically modified to stimulate immunity or to avoid immune recognition, as in the case of vaccine carriers/adjuvants or drug delivery systems, respectively. The aims of this Research Topic is to provide an overview of recent strategies: 1.for assessing the immunosafety of engineered nanomaterials/nanoparticles, in particular in terms of activation of inflammatory responses, such as complement activation and allergic reactions, based on the nanomaterial intrinsic characteristics and on the possible carry-over of bioactive contaminants such as LPS. Production of new nanoparticles taking into account their effects on immune responses, in order to avoid undesirable effects on one hand, and to design particles with desirable effects for medical applications on the other hand; 2.for designing more effective nanomedicines by either avoiding or exploiting their interaction with the immune systems, with particular focus on cancer diagnosis and therapy, and vaccination. This collection of articles gives a comprehensive view of the state-of-the-art of the interaction of nanoparticles with the immune system from the two perspectives of safety and medical use, and aims at providing immunologists with the relevant knowledge for designing improved strategies for immunologically safe nanomaterial applications.

Gene function in schistosomes: recent advances towards a cure

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195565 Year: Pages: 154 DOI: 10.3389/978-2-88919-556-5 Language: English
Publisher: Frontiers Media SA
Subject: Ecology --- Science (General) --- Genetics --- Microbiology
Added to DOAB on : 2016-01-19 14:05:46
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Schistosomes are human parasites distributed worldwide in tropical and sub-tropical latitudes, especially in developing countries and impoverished regions. These neglected tropical disease (NTD) pathogens causes debilitating illnesses, which include hepatosplenomegaly, hepatic fibrosis, haemorrhagic necrotic ulcerations in the intestinal mucosa, urogenital tract diseases, in addition to cardiopulmonary, renal and neurologic lesions due to egg accumulation in the liver, intestines, uro-genital tissues and other sites. Urogenital schistosomiasis is a risk factor for bladder cancer and increases the risk of transmission of HIV infection. Despite extensive effort to control this NTD over the years, deployment on a considerable scale of commercially available drugs in endemic populations has induced the emergence of resistant isolates and raised the need to identify new targets for alternative therapies. Because of the availability of genomes of the three major species of human schistosomiasis, and through advances in functional genomics and live imaging, studies on schistosomes have now come into focus as models to investigate adaptations to parasitism and developmental biology of trematodes and cestodes, and indeed flatworms and Lophotrochozoans, at large. This Research Topic aims at gathering state-of-art essays on schistosome genetics, genetics, pathobiology and immunobiology. It also aims to highlight advances in understanding of the host-parasite relationship, in paradigms that address this NTD, and to discuss new perspectives and advances in chemotherapy and immunoprophylaxis.

How Salmonella infection can inform on mechanisms of immune function and homeostasis

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197996 Year: Pages: 143 DOI: 10.3389/978-2-88919-799-6 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2017-02-03 17:04:57
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The use of model antigens such as haptens and ovalbumin has provided enormous insights into how immune responses develop, particularly to vaccine antigens. Furthermore, these studies are overwhelmingly performed in animals housed in clean facilities and are not known to have experienced overt clinical signs caused by infectious agents. Therefore, this is unlikely to reflect the impact more complex host-pathogen interactions can have on the host, nor the diversity in how immunity is regulated. Humans develop immune responses in the context of the periodic exposure to multiple pathogens and vaccines over a life-time. These are likely to have a long-lasting effect on who and what we are and how we respond to further antigen challenge. Therefore, studies on how infection influences immune homeostasis and how the development of responses to a pathogen reflects what is known on immune regulation will be informative on how we can translate findings from our standard models into treatments usable in humans. One organism allows us to do just this. Bacteria of the genus Salmonella are devastating human pathogens. Nevertheless, many aspects of the diseases they cause can be successfully modelled in murine systems so that the infection is either resolving or non-resolving. This has the advantage of allowing the long-term impact of infection on immune function to be assessed. We propose to welcome key workers to write about their research that examine the consequence of Salmonella infection on the host and the elements of the bacterium that contribute to this.

Travel Medicine - Series 1

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ISBN: 9783038979043 / 9783038979050 Year: Pages: 68 DOI: 10.3390/books978-3-03897-953-1 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Pharmacy and materia medica --- Medicine (General)
Added to DOAB on : 2019-06-26 08:44:06
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This collection of papers describes the recent development of travel health and vaccination services delivered by pharmacists. It is the first dedicated collection of its type and provides a template for the continued growth of pharmacy practice in this area. The articles examine and report on aspects of such services in the UK, US, Canada, Australia, Switzerland, and South Africa, which will provide useful insight for those in other countries developing such pharmacy-based services.

New Advances on Zika Virus Research

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ISBN: 9783038977643 Year: Pages: 552 DOI: 10.3390/books978-3-03897-765-0 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Internal medicine --- Medicine (General)
Added to DOAB on : 2019-04-05 10:34:31
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Zika virus (ZIKV) is a mosquito-borne member of the Flaviviridae family that historically has been associated with mild febrile illness. However, the recent outbreaks in Brazil in 2015 and its rapid spread throughout South and Central America and the Caribbean, together with its association with severe neurological disorders—including fetal microcephaly and Guillain-Barré syndrome in adults—have changed the historic perspective of ZIKV. Currently, ZIKV is considered an important public health concern that has the potential to affect millions of people worldwide. The significance of ZIKV in human health and the lack of approved vaccines and/or antiviral drugs to combat ZIKV infection have triggered a global effort to develop effective countermeasures to prevent and/or treat ZIKV infection. In this Special Issue of Viruses, we have assembled a collection of 32 research and review articles that cover the more recent advances on ZIKV molecular biology, replication and transmission, virus–host interactions, pathogenesis, epidemiology, vaccine development, antivirals, and viral diagnosis.

Keywords

Ziks virus --- silvestrol --- antiviral --- eIF4A --- hepatocytes --- flavivirus --- arbovirus --- Zika --- sexual transmission --- testis --- prostate --- Zika virus --- ZIKV --- rhesus macaques --- Non-human primates --- NHP --- infection --- natural history --- Asian-lineage --- African-lineage --- zika virus --- ZIKV–host interactions --- viral pathogenesis --- cell surface receptors --- antiviral responses --- viral counteraction --- cytopathic effects --- microcephaly --- ZIKV-associated neurologic disorders --- Zika virus --- serology --- flavivirus --- microsphere immunoassay --- validated --- optimised --- dengue virus --- ZIKV --- reporter virus --- cryptic promoter silencing --- full-length molecular clone --- subgenomic replicon --- plasmid toxicity --- Zika virus --- dengue viruses --- flavivirus --- ELISA --- indirect immunofluorescence --- plaque reduction neutralization test --- polymerase chain reaction --- cross-reactions --- Zika virus --- flavivirus --- infectious cDNA --- replication --- gene expression --- neuropathogenesis --- viral genetic variation --- host genetic variation --- flavivirus --- Zika virus --- therapy --- host-directed antivirals --- Aedes aegypti --- RNA-seq --- insecticide resistance --- Zika virus --- detoxification and immune system responses --- Zika virus --- mosquito-borne flavivirus --- emerging arbovirus --- outbreak control --- molecular diagnostics --- laboratory preparedness --- assay standardization --- external quality assessment --- EQA --- QCMD --- flavivirus --- eye --- zika virus --- blood-retinal barrier --- ocular --- innate response --- Zika virus --- pregnancy --- fetal infection --- congenital Zika syndrome --- Asian lineage --- Zika virus --- Full-length cDNA infectious clones --- Bacterial artificial chromosome --- NS2A protein --- Zika virus --- neural progenitor cells --- neurons --- Zika virus --- antivirals --- therapeutics --- research models and tools --- flavivirus --- Zika virus (ZIKV) --- reverse genetics --- infectious clone --- full-length molecular clone --- bacterial artificial chromosome --- replicon --- infectious RNA --- Zika virus --- flavivirus --- arbovirus --- sexual transmission --- host genetic variation --- immune response --- Zika virus --- flaviviruses --- vaccines --- virus like particles --- clinical trials --- ZIKV --- NS1 protein --- Zika virus --- diagnosis --- monoclonal antibodies --- ELISA --- zika virus --- placenta cells --- microglia cells --- siRNA --- TLR7/8 --- Zika --- viral evolution --- genetic variability --- Bayesian analyses --- Zika virus --- reverse genetics --- infectious cDNA --- Tet-inducible --- MR766 --- FSS13025 --- flavivirus --- ZIKV --- NS5 --- type I IFN antagonist --- point-of-care diagnostics --- isothermal nucleic acid amplification --- nucleic acid computation --- nucleic acid strand exchange --- zika virus --- mosquito --- mosquito surveillance --- multiplex nucleic acid detection --- boolean logic-processing nucleic acid probes --- Zika virus --- flavivirus --- astrocytomas --- dsRNA --- viral fitness --- antiviral --- heme-oxygenase 1 --- Zika virus --- viral replication --- Zika virus --- antiviral compounds --- neural cells --- viral replication --- flavivirus --- Zika virus --- viral persistence --- testicular cells --- testes --- Zika virus --- prM-E proteins --- viral pathogenicity --- virus attachment --- viral replication --- viral permissiveness --- viral survival --- apoptosis --- cytopathic effects --- mutagenesis --- chimeric viruses --- human brain glial cells --- Zika virus --- flavivirus --- microRNAs --- neurons --- neuroinflammation --- anti-viral immunity --- Zika virus --- dengue virus --- secondary infections --- cross-reactions --- IgA --- IgG avidity tests

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