Immunization with Synthetic Nanoparticles to Generate Mucosal CD8 T Cell Responses

Immunization with Synthetic Nanoparticles to Generate Mucosal CD8 T Cell Responses PDF Author: Adrienne Victoria Li
Publisher:
ISBN:
Category :
Languages : en
Pages : 110

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Book Description
Vaccines have benefited global health by controlling or eradicating life threatening diseases. With better understanding of infectious diseases and immunity, more interest has been placed on stimulating mucosal immune responses with vaccines as mucosal surfaces function as a first line of defense against infections. Progress made in nanoparticle research, in particular the successful use of liposomes for drug delivery, has made liposomes an attractive candidate for vaccine delivery. Here, we investigate the efficacy of using a novel nanoparticle system, Interbilayer Crosslinked Multilamellar Vesicles (ICMVs), as a mucosal vaccine to stimulate mucosal and systemic CD8 immunity. We first assessed the ability of ICMVs to elicit mucosal CD8 response, against the model antigen ovalbumin (OVA), by administration of the nanoparticles through the lungs. We explored the use of 2 different Toll-like receptor agonists (TLRa), monophosphoryl lipid A (MPLA) and Polyinosinic:polycytidylic acid (poly (I:C) or pIC) added to ICMVs as adjuvants. Pulmonary administration of ICMV with both adjuvants was found to give the most potent CD8 T cell response in both systemic and mucosal compartments. We looked further into the quality of the immune response and detected the presence of antigenspecific memory CD8 T cells in the system at ~2.5 months after immunization. The majority of these cells were found to be effector memory cells (CD44hiCD62Llo) and expressed markers for long term survival (CD127hiKLRG1lo), suggesting that long term protection against infection can be induced by pulmonary delivery of ICMVs. We also explored using this system to deliver a model HIV peptide epitope, AL 1, and ICMV successfully induced CD8 response against this epitope. Animals immunized against AL 11 were challenged with a live virus expressing the same epitope and protection was seen only in the pulmonary ICMV treatment group. Virus was delivered via the lungs and viral titre was decreased in both the lungs and ovaries. Neither the soluble form of the vaccine or ICMV delivered via parenteral injection conferred protection. Safety of the ICMV system was also assessed and no significant negative effects were observed in body weight and histological analysis on lungs. Finally, mechanism of using nanoparticles as pulmonary vaccines was investigated to gain better understanding in how particulate vaccine and route of immunization improved the efficacy of a vaccine. Overall, this thesis describes a comprehensive study of systemic and mucosal CD8 responses generated by pulmonary delivery of a novel nanoparticle system. This data provides evidence that mucosal delivery of ICMVs can safely and effectively stimulate disseminated mucosal CD8+ T cells at sites relevant for protection against mucosal infection. A better understanding of nanoparticles for pulmonary immunization was also gained.

Mucosal Vaccines

Mucosal Vaccines PDF Author: Hiroshi Kiyono
Publisher: Academic Press
ISBN:
Category : Medical
Languages : en
Pages : 528

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Book Description
This comprehensive, authoritative treatise covers all facets of mucosal vaccines including their development, mechanisms of action, molecular/cellular aspects, and practical applications. The contributing authors and editors of this one-of-a-kind book are very well known in their respective fields. Mucosal Vaccines is organized in a unique format in which with basic, clinical, and practical aspects of the mucosal immune system for vaccine development are described and discussed. This project is endorsed by the Society for Mucosal Immunology. Key Features Provides the latest views on mucosal vaccines Applies basic principles to the development of new vaccines Links basic, clinical, and practical aspects of mucosal vaccines to different infectious diseases Unique and user-friendly organization

Micro- and Nanotechnology in Vaccine Development

Micro- and Nanotechnology in Vaccine Development PDF 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

Immunotherapy and Vaccines

Immunotherapy and Vaccines PDF Author: Stanley J. Cryz
Publisher: Wiley-VCH
ISBN:
Category : Medical
Languages : en
Pages : 172

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Book Description


The Science and Applications of Synthetic and Systems Biology

The Science and Applications of Synthetic and Systems Biology PDF Author: Institute of Medicine
Publisher: National Academies Press
ISBN: 0309219396
Category : Science
Languages : en
Pages : 570

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Book Description
Many potential applications of synthetic and systems biology are relevant to the challenges associated with the detection, surveillance, and responses to emerging and re-emerging infectious diseases. On March 14 and 15, 2011, the Institute of Medicine's (IOM's) Forum on Microbial Threats convened a public workshop in Washington, DC, to explore the current state of the science of synthetic biology, including its dependency on systems biology; discussed the different approaches that scientists are taking to engineer, or reengineer, biological systems; and discussed how the tools and approaches of synthetic and systems biology were being applied to mitigate the risks associated with emerging infectious diseases. The Science and Applications of Synthetic and Systems Biology is organized into sections as a topic-by-topic distillation of the presentations and discussions that took place at the workshop. Its purpose is to present information from relevant experience, to delineate a range of pivotal issues and their respective challenges, and to offer differing perspectives on the topic as discussed and described by the workshop participants. This report also includes a collection of individually authored papers and commentary.

Subunit Vaccine Delivery

Subunit Vaccine Delivery PDF 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.

Immunopotentiators in Modern Vaccines

Immunopotentiators in Modern Vaccines PDF Author: Virgil Schijns
Publisher: Elsevier
ISBN: 0080457215
Category : Medical
Languages : en
Pages : 396

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Book Description
Immunopotentiators in Modern Vaccines provides an in-depth insight and overview of a number of most promising immunopotentiators in modern vaccines. In contrast to existing books on the subject it provides recent data on the critical mechanisms governing the activity of vaccine adjuvants and delivery systems. Knowledge of immunological pathways and scenarios of the cells and molecules involved is described and depicted in comprehensive illustrations. Contributions from leading international authorities in the field Well-illustrated, informative figures present the interactions between immunopotentiators and the host immune system Each chapter lists advantages and potential hurdles for achieving a practical application for the specific immunopentiator

Vaccine Adjuvants and Delivery Systems

Vaccine Adjuvants and Delivery Systems PDF 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.

Pharmaceutical Biotechnology

Pharmaceutical Biotechnology PDF Author: Daan J. A. Crommelin
Publisher: CRC Press
ISBN: 9780415285018
Category : Medical
Languages : en
Pages : 456

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Book Description
The field of pharmaceutical biotechnology is evolving rapidly. A whole new arsenal of protein pharmaceuticals is being produced by recombinant techniques for cancer, viral infections, cardiovascular and hereditary disorders, and other diseases. In addition, scientists are confronted with new technologies such as polymerase chain reactions, combinatorial chemistry and gene therapy. This introductory textbook provides extensive coverage of both the basic science and the applications of biotechnology-produced pharmaceuticals, with special emphasis on their clinical use. Pharmaceutical Biotechnology serves as a complete one-stop source for undergraduate pharmacists, and it is valuable for researchers and professionals in the pharmaceutical industry as well.

Oligonucleotide-Based Drugs and Therapeutics

Oligonucleotide-Based Drugs and Therapeutics PDF Author: Nicolay Ferrari
Publisher: John Wiley & Sons
ISBN: 1118537335
Category : Medical
Languages : en
Pages : 576

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Book Description
A comprehensive review of contemporary antisense oligonucleotides drugs and therapeutic principles, methods, applications, and research Oligonucleotide-based drugs, in particular antisense oligonucleotides, are part of a growing number of pharmaceutical and biotech programs progressing to treat a wide range of indications including cancer, cardiovascular, neurodegenerative, neuromuscular, and respiratory diseases, as well as other severe and rare diseases. Reviewing fundamentals and offering guidelines for drug discovery and development, this book is a practical guide covering all key aspects of this increasingly popular area of pharmacology and biotech and pharma research, from the basic science behind antisense oligonucleotides chemistry, toxicology, manufacturing, to safety assessments, the design of therapeutic protocols, to clinical experience. Antisense oligonucleotides are single strands of DNA or RNA that are complementary to a chosen sequence. While the idea of antisense oligonucleotides to target single genes dates back to the 1970's, most advances have taken place in recent years. The increasing number of antisense oligonucleotide programs in clinical development is a testament to the progress and understanding of pharmacologic, pharmacokinetic, and toxicologic properties as well as improvement in the delivery of oligonucleotides. This valuable book reviews the fundamentals of oligonucleotides, with a focus on antisense oligonucleotide drugs, and reports on the latest research underway worldwide. • Helps readers understand antisense molecules and their targets, biochemistry, and toxicity mechanisms, roles in disease, and applications for safety and therapeutics • Examines the principles, practices, and tools for scientists in both pre-clinical and clinical settings and how to apply them to antisense oligonucleotides • Provides guidelines for scientists in drug design and discovery to help improve efficiency, assessment, and the success of drug candidates • Includes interdisciplinary perspectives, from academia, industry, regulatory and from the fields of pharmacology, toxicology, biology, and medicinal chemistry Oligonucleotide-Based Drugs and Therapeutics belongs on the reference shelves of chemists, pharmaceutical scientists, chemical biologists, toxicologists and other scientists working in the pharmaceutical and biotechnology industries. It will also be a valuable resource for regulatory specialists and safety assessment professionals and an important reference for academic researchers and post-graduates interested in therapeutics, antisense therapy, and oligonucleotides.