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Author: Pamela Antonia Basto
Publisher:
ISBN:
Category :
Languages : en
Pages : 120
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Book Description
Vaccines have revolutionized medicine by increasing the life expectancy of children and substantially decreasing the morbidity of multiple infectious diseases worldwide. Over several decades, we have acquired significant gains in the understanding of the underlying mechanisms involved in developing protective immunity, yet vaccine development has progressed comparatively slowly. This thesis serves to explore two polymeric nanoparticle platforms to demonstrate the therapeutic potential of synthetic nanocarriers as vaccines with the aim of 1) providing greater spatiotemporal release of small molecule adjuvant to secondary lymphoid sites and 2) providing a tunable surface for loading B cell antigen epitopes in a specific conformation to drive epitope-specific antibody response. In recent decades, TLR mechanisms have been elucidated and novel agonists have been developed, yet our generation still has not seen paramount progress in the clinical translation of these agonists due to risks of systemic toxicity and off target effects. In the first section, we synthesized 223±18 nm poly(lactic-co-glycolic acid)- poly(ethylene glycol)/ poly(lactic acid)-R848 (PLGA-PEG/PLA-R848) nanoparticle vaccine that is designed to deliver a combination of antigen and control release of a small molecule adjuvant R848 (tl/2= 42 hours) to drive a potent antigen-specific immune response. Using ovalbumin as a model protein, this vaccine is able to enhance antigen presentation and co-stimulatory molecules on dendritic cells and subsequently enhanced proliferation of antigen-specific naive CD8+ cells in vitro. Upon vaccination, our delivery system is able to increase cell-mediated and humoral response in comparison to its soluble form, thereby illustrating the potential to bring novel small molecule adjuvants to the clinics. In the second section, we developed a nanoparticle vaccine platform that allows selective orientation of peptide epitopes to enhance B cell response in an application that has therapeutic potential for treatment for cardiovascular disease (CVD). Utilizing epitopes discovered through in silico modeling for human PCSK9, a plasma protein that plays an important role in LDL cholesterol (LDL-c) levels in the blood, our nanoparticle allows selective orientation through biotin-streptavidin conjugation. Upon vaccination with CPG, selected synthetic epitopes conjugated to polymeric nanoparticles trended to reduce serum LDL-c and serum PCSK9 in murine models. Additionally, antibodies in the serum showed promise to increase LDL-receptor levels in HepG2 cells transfected in with WT-hPCSK9 and GOF-hPCSK9 separately suggesting that this vaccine has the potential to reduce risks of CVD. These studies demonstrate that designing polymeric nanoparticles for applications to stimulate the immune system can help define new, cost-effective treatment options in applications for prophylaxis against infectious diseases that are unresponsive to traditional routes of vaccination or for immunotherapy against cardiovascular disease and cancer.
Author: Pamela Antonia Basto
Publisher:
ISBN:
Category :
Languages : en
Pages : 120
Get Book Here
Book Description
Vaccines have revolutionized medicine by increasing the life expectancy of children and substantially decreasing the morbidity of multiple infectious diseases worldwide. Over several decades, we have acquired significant gains in the understanding of the underlying mechanisms involved in developing protective immunity, yet vaccine development has progressed comparatively slowly. This thesis serves to explore two polymeric nanoparticle platforms to demonstrate the therapeutic potential of synthetic nanocarriers as vaccines with the aim of 1) providing greater spatiotemporal release of small molecule adjuvant to secondary lymphoid sites and 2) providing a tunable surface for loading B cell antigen epitopes in a specific conformation to drive epitope-specific antibody response. In recent decades, TLR mechanisms have been elucidated and novel agonists have been developed, yet our generation still has not seen paramount progress in the clinical translation of these agonists due to risks of systemic toxicity and off target effects. In the first section, we synthesized 223±18 nm poly(lactic-co-glycolic acid)- poly(ethylene glycol)/ poly(lactic acid)-R848 (PLGA-PEG/PLA-R848) nanoparticle vaccine that is designed to deliver a combination of antigen and control release of a small molecule adjuvant R848 (tl/2= 42 hours) to drive a potent antigen-specific immune response. Using ovalbumin as a model protein, this vaccine is able to enhance antigen presentation and co-stimulatory molecules on dendritic cells and subsequently enhanced proliferation of antigen-specific naive CD8+ cells in vitro. Upon vaccination, our delivery system is able to increase cell-mediated and humoral response in comparison to its soluble form, thereby illustrating the potential to bring novel small molecule adjuvants to the clinics. In the second section, we developed a nanoparticle vaccine platform that allows selective orientation of peptide epitopes to enhance B cell response in an application that has therapeutic potential for treatment for cardiovascular disease (CVD). Utilizing epitopes discovered through in silico modeling for human PCSK9, a plasma protein that plays an important role in LDL cholesterol (LDL-c) levels in the blood, our nanoparticle allows selective orientation through biotin-streptavidin conjugation. Upon vaccination with CPG, selected synthetic epitopes conjugated to polymeric nanoparticles trended to reduce serum LDL-c and serum PCSK9 in murine models. Additionally, antibodies in the serum showed promise to increase LDL-receptor levels in HepG2 cells transfected in with WT-hPCSK9 and GOF-hPCSK9 separately suggesting that this vaccine has the potential to reduce risks of CVD. These studies demonstrate that designing polymeric nanoparticles for applications to stimulate the immune system can help define new, cost-effective treatment options in applications for prophylaxis against infectious diseases that are unresponsive to traditional routes of vaccination or for immunotherapy against cardiovascular disease and cancer.
Author: Harvinder Singh Gill
Publisher: Springer Nature
ISBN: 3030850676
Category : Medical
Languages : en
Pages : 140
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Book Description
This book introduces nanoparticles as a powerful platform for vaccine design. Current challenges in vaccine development are discussed and the unique advantages nanoparticles provide in overcoming these challenges are explored. The authors offer fascinating insights into the immunological assets of using nanoparticles as delivery vehicles or adjuvants and present different materials that are being used in nanoparticle-based vaccine development, covering peptides, proteins, polymers, virus-like particles, and liposomes. Its contemporary research insights and practical examples for applications make this volume an inspiring read for researchers and clinicians in vaccinology and immunology. Chapter "Liposome Formulations as Adjuvants for Vaccines" is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
Author: Mariusz Skwarczynski
Publisher: William Andrew
ISBN: 0323400299
Category : Medical
Languages : en
Pages : 462
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Book Description
This book provides a comprehensive overview of how use of micro- and nanotechnology (MNT) has allowed major new advance in vaccine development research, and the challenges that immunologists face in making further progress. MNT allows the creation of particles that exploit the inherent ability of the human immune system to recognize small particles such as viruses and toxins. In combination with minimal protective epitope design, this permits the creation of immunogenic particles that stimulate a response against the targeted pathogen. The finely tuned response of the human immune system to small particles makes it unsurprising that many of the lead adjuvants and vaccine delivery systems currently under investigation are based on nanoparticles. Provides a comprehensive and unparalleled overview of the role of micro- and nanotechnology in vaccine development Allows researchers to quickly familiarize themselves with the broad spectrum of vaccines and how micro- and nanotechnologies are applied to their development Includes a combination of overview chapters setting out general principles, and focused content dealing with specific vaccines, making it useful to readers from a variety of disciplines
Author: National Academies of Sciences, Engineering, and Medicine
Publisher: National Academies Press
ISBN: 0309450063
Category : Medical
Languages : en
Pages : 137
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Book Description
The most recent Ebola epidemic that began in late 2013 alerted the entire world to the gaps in infectious disease emergency preparedness and response. The regional outbreak that progressed to a significant public health emergency of international concern (PHEIC) in a matter of months killed 11,310 and infected more than 28,616. While this outbreak bears some unique distinctions to past outbreaks, many characteristics remain the same and contributed to tragic loss of human life and unnecessary expenditure of capital: insufficient knowledge of the disease, its reservoirs, and its transmission; delayed prevention efforts and treatment; poor control of the disease in hospital settings; and inadequate community and international responses. Recognizing the opportunity to learn from the countless lessons of this epidemic, the National Academies of Sciences, Engineering, and Medicine convened a workshop in March 2015 to discuss the challenges to successful outbreak responses at the scientific, clinical, and global health levels. Workshop participants explored the epidemic from multiple perspectives, identified important questions about Ebola that remained unanswered, and sought to apply this understanding to the broad challenges posed by Ebola and other emerging pathogens, to prevent the international community from being taken by surprise once again in the face of these threats. This publication summarizes the presentations and discussions from the workshop.
Author: Manmohan Singh
Publisher: John Wiley & Sons
ISBN: 0470134925
Category : Science
Languages : en
Pages : 470
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Book Description
The authoritative reference on recent developments in vaccinology New technologies, including recombinant protein and DNA, have sparked phenomenal progress in vaccine development and delivery systems. This unique resource brings scientists up to date on recent advances and provides the information they need to select candidate adjuvants. With chapters written by leading experts in their fields, Vaccine Adjuvants and Delivery Systems: * Provides a comprehensive overview of the rapidly evolving field and developing formulation methods * Covers cutting-edge technologies and gives the current status of adjuvants in clinical trials and those still in the pre-clinical stage * Includes detailed information on specific vaccine adjuvants, including MF59, TLR4 agonists, new iscoms, cytokines, polyphosphazenes, and more * Provides a historical perspective on the development of vaccine adjuvants and discusses the mechanisms of adjuvant actions * Covers some novel adjuvants and delivery systems and the safety evaluation of adjuvants A great reference for researchers, scientists, and students in vaccinology, biotechnology, immunology, and molecular biology, this resource is also valuable for researchers and scientists in veterinary medicine who work to prevent diseases in animals.
Author: Camilla Foged
Publisher: Springer
ISBN: 1493914170
Category : Medical
Languages : en
Pages : 433
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Book Description
This comprehensive volume compiles the concepts essential for the understanding of the pharmaceutical science and technology associated with the delivery of subunit vaccines. Twenty-one chapters are divided into four main parts: (I) Background; (2) Delivery Systems for Subunit Vaccines; (3) Delivery Routes, Devices and Dosage Forms; and (4) Pharmaceutical Analysis and Quality Control of Vaccines. Part one provide a basic background with respect to immunology and general vaccine classification. In part two, it presents representative types of vaccine delivery systems individually with focus on the physicochemical properties of the systems and their significance for the immune response they stimulate. These delivery systems include aluminum adjuvants, emulsions, liposomes, bilosomes, cubosomes/hexosomes, ISCOMs, virus-like particles, polymeric nano- and microparticles, gels, implants and cell-based delivery systems. Following these chapters, part three addresses the challenges associated with vaccine delivery via specific routes of administration—in particular subcutaneous, intramuscular, oral, nasal, pulmonary, transdermal and vaginal administration. Furthermore, the specific administration routes are discussed in combination with device technologies relevant for the respective routes as well as dosage forms appropriate for the device technology. Finally, the fourth part concerns pharmaceutical analysis and quality control of subunit vaccines.
Author: Ijeoma F. Uchegbu
Publisher: Springer Science & Business Media
ISBN: 1461491649
Category : Medical
Languages : en
Pages : 602
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Book Description
Nanoscience or the science of the very small offers the pharmaceutical scientist a wealth of opportunities. By fabricating at the nanoscale, it is possible to exert unprecedented control on drug activity. This textbook will showcase a variety of nanosystems working from their design and construction to their application in the field of drug delivery. The book is intended for graduate students in drug delivery, physical and polymer chemistry, and applied pharmaceutical sciences courses that involve fundamental nanoscience. The purpose of the text is to present physicochemical and biomedical properties of synthetic polymers with an emphasis on their application in polymer therapeutics i.e., pharmaceutical nanosystems, drug delivery and biological performance. There are two main objectives of this text. The first is to provide advanced graduate students with knowledge of the principles of nanosystems and polymer science including synthesis, structure, and characterization of solution and solid state properties. The second is to describe the fundamentals of therapeutic applications of polymers in drug delivery, targeting, response modifiers as well as regulatory issues. The courses, often listed as Advanced Drug Delivery and Applied Pharmaceutics; Polymer Therapeutics; or Nanomedicine, are designed as an overview of the field specifically for graduate students in the Department of Pharmaceutical Sciences Graduate Programs. However, the course content may also be of interest for graduate students in related biomedical research programs. These courses generally include a discussion of the major principles of polymer science and fundamental concepts of application of polymers as modern therapeutics. All courses are moving away from the above mentioned course names and going by ‘pharmaceutical nanoscience or nanosystems’. This area of research and technology development has attracted tremendous attention during the last two decades and it is expected that it will continue to grow in importance. However, the area is just emerging and courses are limited but they are offered.
Author: Flavia Fontana
Publisher: Springer Nature
ISBN: 3030581748
Category : Medical
Languages : en
Pages : 358
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Book Description
The book covers the latest developments in biologically-inspired and derived nanomedicine for cancer therapy. The purpose of the book is to illustrate the significance of naturally-mimicking systems for enhancing the dose delivered to the tumor, to improve stability, and prolong the circulation time. Moreover, readers are presented with advanced materials such as adjuvants for immunostimulation in cancer vaccines. The book also provides a comprehensive overview of the current status of academic research. This is an ideal book for students, researchers, and professors working in nanotechnology, cancer, targeted drug delivery, controlled drug release, materials science, and biomaterials as well as companies developing cancer immunotherapy.
Author: Vinod Kumar Yata
Publisher: Springer Nature
ISBN: 3030471209
Category : Technology & Engineering
Languages : en
Pages : 340
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Book Description
This book is the third volume on this subject and focuses on the recent advances of nanopharmaceuticals in cancer, dental, dermal and drug delivery applications and presents their safety, toxicity and therapeutic efficacy. The book also includes the transport phenomenon of nanomaterials and important pathways for drug delivery applications. It goes on to explain the toxicity of nanoparticles to different physiological systems and methods used to assess this for different organ systems using examples of in vivo systems.
Author: Heung Jae Chun
Publisher: Springer
ISBN: 9811309507
Category : Medical
Languages : en
Pages : 493
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Book Description
This book explores in depth the latest enabling technologies for regenerative medicine. The opening section examines advances in 3D bioprinting and the fabrication of electrospun and electrosprayed scaffolds. The potential applications of intelligent nanocomposites are then considered, covering, for example, graphene-based nanocomposites, intrinsically conductive polymer nanocomposites, and smart diagnostic contact lens systems. The third section is devoted to various drug delivery systems and strategies for regenerative medicine. Finally, a wide range of future enabling technologies are discussed. Examples include temperature-responsive cell culture surfaces, nanopatterned scaffolds for neural tissue engineering, and process system engineering methodologies for application in tissue development. This is one of two books to be based on contributions from leading experts that were delivered at the 2018 Asia University Symposium on Biomedical Engineering in Seoul, Korea – the companion book examines in depth novel biomaterials for regenerative medicine.
