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Particle-based delivery of antigen has great potential for generating improved vaccines. During the course of an immune response, a pathogen may trigger multiple pattern-recognition receptors, instilling a strong proinflammatory immune response. Highly successful vaccines, such yellow fever vaccine and Dryvax® (smallpox), also induce immune responses by utilizing multiple pathogen-sensing signaling pathways, yielding long-lasting B and T cell responses. Subunit vaccines generally require an external adjuvant to boost immune responses; however, recent data has shown that targeting multiple immune activation pathways generates a more potent immune response, similar to native infection or immunization with live vaccines (Kasturi et al., 2011; Ahonen et al., 2004, 2008). To determine the effects of presenting targeting and/or activating moieties in a multivalent form, we generated two different particle-based vaccines. The first, an antigen-loaded, pH-sensitive hydrogel microparticle, was found to be taken up and presented by bone marrow-derived dendritic cells (BMDCs) in vitro and targeted to dendritic cells (DCs) and monocytes in vivo. Addition of targeting antibodies to the particle surface did not influence its uptake. DCs also upregulated activation markers when treated with microparticles, even when no agonistic anti-CD40 was conjugated to the microparticles. Furthermore, these particles induced increased percentages of interferon-[gamma]-producing CD8 T cells in response to challenge with a pathogen expressing the same antigen, in both an accelerated vaccination strategy using pre-loaded BMDCs and a traditional mouse immunization setting. The second particle, a luminescent porous silicon nanoparticle, displayed the same targeting and/or activating antibodies. This particle used antigen that was encoded in the 3' end of the targeting antibody instead of encapsulating it in the particle. Nanoparticles displaying agonistic anti-CD40 (with no antigen), produced a multivalent effect in B cells in vitro, in which the stimulatory effects of the CD40 nanoparticle were observed at 30-40-fold lower dose of antibody versus free anti-CD40. In vitro and in vivo, nanoparticles displaying targeting antibodies induced CD8 T cell proliferation better than those displaying control antibodies; however, this effect could not be consistently observed long-term in vivo, even with both targeting antibody and anti-CD40. In fact antigen-specific cells were most often deleted at memory time points.
Epidermal Langerhans Cells focuses on epidermal Langerhans cells (LCs) and the important role they play in the induction of contact hypersensitivity and graft rejection. This in-depth work discusses how these antigen-presenting cells are modulated by various physicochemical agents (such as UV light) and how they can be infected by the AIDS virus. It also reveals that cytokines mediate their development into potent T cell-stimulatory dendritic cells. This comprehensive review covers important experimental details and methods, and fascinating information on LCs. It also provides an overview of the immune system as it relates to the skin in health and disease. This up-to-date publication is an indispensable resource for all investigative and clinical dermatologists, as well as immunologists interested in antigen-presenting cells.
Particle-mediated epidermal delivery (PMED) of DNA vaccines is based on the acceleration of DNA-coated gold directly into the cytoplasm and nuclei of living cells of the epidermis, facilitating DNA delivery and gene expression. Professional antigen-presenting cells and keratinocytes in the skin are both targeted, resulting in antigen presentation via direct transfection and cross-priming mechanisms. Only a small number of cells need to be transfected to elicit humoral, cellular and memory responses, requiring only a low DNA dose. In recent years, data have accumulated on the utility of PMED for delivery of DNA vaccines against a number of viral pathogens, including filoviruses, flaviviruses, poxviruses, togaviruses and bunyaviruses. PMED DNA vaccination of rodents and nonhuman primates results in the generation of neutralizing antibody, cellular immunity, and protective efficacy against a broad range of viruses of public health concern.
This comprehensive, authoritative treatise covers all aspects 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 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. - 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
This volume of Current Topics in Microbiology and Immunology covers diverse topics related to intradermal immunization. The chapters highlight the effectiveness of intradermal immunization in experimental animal models or in clinical practice, all supporting the view that intradermal immunization is at least as good as other immunization routes. Keeping in mind that current vaccines are not specially designed for intradermal immunization, but show comparable efficiency even at reduced dosages, this underlines the great potential for the skin as a vaccination site. Hopefully, the overview in this volume will encourage vaccine designers to focus on this promising immunization route, and in addition, to inspire them to develop vaccines that are especially optimized for intradermal immunization.
Our immune system is essential for the protection against and destruction of pathogens, but also has an important role in cancer and tumor control. Therapy that is committed to use the immune system as anti-cancer strategy is called immunotherapy. Effective immunotherapy depends on the induction and activation of both innate (non-specific) and adaptive (specific and memory) immunity simultaneously combined with inhibition of tumor induced immune suppression. Vaccination, widely applied in the field of virology, can also be exploited in cancer to provide activation signals to the innate and adaptive immune players. Central players of innate and adaptive immunity that need to be instructed by vaccines are antigen presenting cells (APCs) such as dendritic cells (DCs) or Langerhans cells, which are both located in the skin, the prime vaccination site. APCs can be seen as messengers of the immune system that take up antigens, either tumor or pathogen derived, process and present them to T-cells that belong to the adaptive immunity and create specifity and memory. Stimulation of APCs facilitates their migration to lymph nodes where they can establish activation of innate immune cells, such as invariant natural killer T-cells (iNKT) in addition to activation of the adaptive immune response trough cross-presentation of antigens to CD8+ and CD4+ T-cells. These CD8+ and CD4+ T-cells can be respectively seen as effector cells that can kill tumor cells and helper cells that support CD8+ T-cells. iNKT can be described as immune boosters that aid in activation of both CD8+ and CD4+ T-cells, but also DCs and natural killer cells (which can kill tumor cells) but above all iNKT also exert killing capacities themselves. Since APCs play such a central role in the activation of antigen specific T-cell responses and iNKT, it is an attractive strategy to develop vaccines that are specifically delivered to APCs.
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
Rapid progress in the definition of tumor antigens, and improved immunization methods, bring effective cancer vaccines within reach. In this wide-ranging survey, leading clinicians and scientists review therapeutic cancer vaccine strategies against a variety of diseases and molecular targets. Intended for an interdisciplinary readership, their contributions cover the rationale, development, and implementation of vaccines in human cancer treatment, with specific reference to cancer of the cervix, breast, colon, bladder, and prostate, and to melanoma and lymphoma. They review target identification, delivery vectors and clinical trial design. The book begins and ends with lucid overviews from the editors, that discuss the most recent developments.
In 1900, for every 1,000 babies born in the United States, 100 would die before their first birthday, often due to infectious diseases. Today, vaccines exist for many viral and bacterial diseases. The National Childhood Vaccine Injury Act, passed in 1986, was intended to bolster vaccine research and development through the federal coordination of vaccine initiatives and to provide relief to vaccine manufacturers facing financial burdens. The legislation also intended to address concerns about the safety of vaccines by instituting a compensation program, setting up a passive surveillance system for vaccine adverse events, and by providing information to consumers. A key component of the legislation required the U.S. Department of Health and Human Services to collaborate with the Institute of Medicine to assess concerns about the safety of vaccines and potential adverse events, especially in children. Adverse Effects of Vaccines reviews the epidemiological, clinical, and biological evidence regarding adverse health events associated with specific vaccines covered by the National Vaccine Injury Compensation Program (VICP), including the varicella zoster vaccine, influenza vaccines, the hepatitis B vaccine, and the human papillomavirus vaccine, among others. For each possible adverse event, the report reviews peer-reviewed primary studies, summarizes their findings, and evaluates the epidemiological, clinical, and biological evidence. It finds that while no vaccine is 100 percent safe, very few adverse events are shown to be caused by vaccines. In addition, the evidence shows that vaccines do not cause several conditions. For example, the MMR vaccine is not associated with autism or childhood diabetes. Also, the DTaP vaccine is not associated with diabetes and the influenza vaccine given as a shot does not exacerbate asthma. Adverse Effects of Vaccines will be of special interest to the National Vaccine Program Office, the VICP, the Centers for Disease Control and Prevention, vaccine safety researchers and manufacturers, parents, caregivers, and health professionals in the private and public sectors.
The induction of antigen-specific immune responses after in vivo transfection with expression plasmids has triggered a revolution of vaccine research. After a first hype, evoked by the fascinating options of this method, clinical studies did not reach the ambitious aims and a phase of disillusion ensued. It became obvious that Gene vaccines displayed a weaker immunogenicity in humans than had been observed in the mouse models. Meanwhile these hurdles have been overcome and gene vaccines undergo a renaissance. The present book gives an update of the “world of naked gene vaccines”, namely DNA and RNA vaccines. Its content ranges from general mechanisms, inherent immunostimulatory properties and the vast potential to modulate immune responses, to recent successful clinical studies and approved veterinary gene vaccines. Beyond the state-of-the-art of genetic immunization, the reader will be stimulated with a chapter addressing “burning questions”.