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Immunization plays a key role in maintaining human health and each year, saves millions of lives from lethal pathogens and other fatal diseases in the most economical way, thanks to the advanced development of model vaccines. Subunit vaccines are regarded as a safer product than the whole microbe based-conventional vaccines and can be entrapped in various nanocarriers to form a vaccine adjuvant-delivery system (VADS) able to further boost their immunostimulatory activity. In this book, six groups of authors introduce immunization advances in VADSs designed for infection prophylaxis and cancer immunotherapy, problems and their resolution in both human and poultry immunization, and also, the mathematical model for assay of the basic immunization problem (BIP) understood from a finance point of view.

Immunological adjuvants. --- Immunization. --- Drug delivery systems. --- Delivery systems, Drug --- Drug administration technology --- Drug delivery technology --- Drugs --- Pharmaceutical technology --- Immunisation --- Immunity --- Immunotherapy --- Adjuvants (Immunology) --- Adjuvants, Immunologic --- Adjuvants, Immunological --- Immune adjuvants --- Immunoactivators --- Immunoadjuvants --- Immunologic adjuvants --- Immunomodulators --- Immunopotentiators --- Immunostimulants --- Biological response modifiers --- Delivery systems --- Medicine --- Public Health --- Preventive Healthcare --- Health Sciences

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In his 1962 book "The Structure of Scientific Revolutions", Thomas Kuhn famously argued that researchers in every field of scientific enquiry always operate under a set of presuppositions known as paradigms that are rarely explicitly stated. In the field of HIV vaccine research, several prevailing paradigms led scientists for many years to pursue unfruitful lines of investigations that impeded significant progress. The uncritical acceptance of reigning paradigms makes scientists reluctant to abandon their mistaken assumptions even when they obtain results that are not consistent with the paradigms. The following five paradigms which disregard the degeneracy of the immune system were particularly harmful. 1) There is a primary and intrinsic epitope specific for each B cell receptor and for the corresponding monoclonal antibody. In reality, there is no single, intrinsic or "real" epitope for any antibody but only a diverse group of potential ligands. 2) Reactions with monoclonal antibodies are more specific than the combined reactivity of polyclonal antibodies. In reality, a polyclonal antiserum has greater specificity for a multiepitopic protein because different antibodies in the antiserum recognize separate epitopes on the same protein, giving rise to an additive specificity effect. By focusing vaccine design on single epitope-Mab pairs, the beneficial neutralizing synergy that occurs with polyclonal antibody responses is overlooked. 3) The HIV epitope identified by solving the crystallographic structure of a broadly neutralizing Mab – HIV Env complex should be able, when used as immunogen, to elicit antibodies endowed with the same neutralizing capacity as the Mab. Since every anti HIV bnMab is polyspecific, the single epitope identified in the complex is not necessarily the one that elicited the bnMab. Since hypermutated Mabs used in crystallographic studies differ from their germline-like receptor version present before somatic hypermutation, the identified epitope will not be an effective vaccine immunogen. 4) Effective vaccine immunogenicity can be predicted from the antigenic binding capacity of viral epitopes. Most fragments of a viral antigen can induce antibodies that react with the immunogen, but this is irrelevant for vaccination since these antibodies rarely recognize the cognate, intact antigen and even more rarely neutralize the infectivity of the viral pathogen that harbors the antigen. 5) The rational design of vaccine immunogens using reverse vaccinology is superior to the trial-and-error screening of vaccine candidates able to induce protective immunity. One epitope can be designed to increase its structural complementarity to one particular bnMab, but such antigen design is only masquerading as immunogen design because it is assumed that antigenic reactivity necessarily entails the immunogenic capacity to elicit neutralizing antibodies. When HIV Env epitopes, engineered to react with a bnMab are used to select from human donors rare memory B cells secreting bnAbs, this represents antigen design and not immunogen design. The aim of this Research Topic is to replace previous misleading paradigms by novel ones that better fit our current understanding of immunological specificity and will help HIV vaccine development.

HIV tolerogenic vaccine --- germline antibodies --- SIV vaccine --- Mucosal vaccine --- Therapeutic vaccine --- vaccine efficacy trials --- neutralizing antibodies --- structure-based reverse vaccinology --- antibody polyspecificity --- bacterial adjuvants

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vaccine --- adjuvants --- Sporothrix schenckii --- toluene --- virulence --- enolase --- Montanide PetGel A --- Amphotericin B --- cutaneous leishmaniasis --- hydrogel --- wound dressing --- controlled release --- thermoreversible gel --- poloxamer 407 --- candidiasis --- amphotericin B --- skin and vaginal mucosa --- butenafine --- SNEDDS --- solid SNEDDS --- spray drying --- leishmaniasis --- design of experiments --- orodispersible films --- fast-dissolving films --- micelles --- fungal infections --- aspergillosis --- oral delivery --- chitosan --- shiitake --- Lentinula edodes --- AHCC® --- Molecular Envelope Technology --- praziquantel --- calcium carbonate --- schistosomiasis --- bioavailability --- solubility --- cytotoxicity --- fluconazole --- orthopedic infection --- Poly(d,l-lactide-co-glycolide) beads --- sustained release --- Leishmania infantum --- meglumine antimoniate --- Sepigel 305® --- topical treatment --- polymer micelles --- drug delivery --- liposomes --- transferosomes --- nanoparticles --- emulsions --- azoles --- combined therapy --- quality by design --- malaria --- trypanosomiasis

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DNA is a rapidly developing vaccine platform for cancer and infectious and non-infectious diseases. Plasmids are used as immunogens to encode proteins to be further synthesized in vaccine recipients. DNA is mainly synthetic, ensuring enhanced expression in the cells of vaccine recipients (mostly mammalians). Their introduction into the host induces antibody and cellular responses. The latter are often more pronounced, and mimic the events occurring in infection, especially viral. There are a few distinct ways in which the vaccine antigen can be processed and presented, which determine the resulting immune response and which can be manipulated. Routinely, the antigen synthesized within the host cell is processed by proteasome, loaded onto, and presented in a complex with MHC I molecules. Processing can be re-routed to the lysosome, or immunogen can be secreted for further presentation in a complex with MHC II. Apart from expression, vaccination efficacy depends on DNA delivery. DNA immunogens are generally administered by intramuscular or intradermal injections, usually followed by electroporation, which enhances delivery 1000-fold. Other techniques are also used, such as noninvasive introduction by biojectors, skin applications with plasters and microneedles/chips, sonication, magnetofection, and even tattooing. An intense debate regarding the pros and cons of different routes of delivery is ongoing. A number of studies have compared the effect of delivery methods at the level of immunogen expression, and the magnitude and specificity of the resulting immune response. According to some, the delivery route determines immunogenic performance; according to others, it can modulate the level of response, but not its specificity or polarity. The progress of research aiming at the optimization of DNA vaccine design, delivery, and immunogenic performance has led to a marked increase in their efficacy in large species and humans. New DNA vaccines for use in the treatment of infectious diseases, cancer, allergies, and autoimmunity are forthcoming. This Special Issue covers various aspects of DNA vaccine development.

alphaviruses --- layered RNA/DNA vectors --- DNA vaccines --- RNA replicons --- recombinant particles --- tumor regression --- protection against tumor challenges and infectious agents --- ebola virus disease --- artificial T-cell antigens --- DNA vaccine constructs --- computer design --- gene expression --- immunogenicity --- DNA vaccine --- mRNA vaccine --- plasmid DNA --- in vitro transcribed mRNA --- immune responses --- formulations --- Cytolytic T Lymphocytes --- antibodies --- innate immunity --- adjuvants --- vaccine delivery --- plasmid --- cytolytic --- perforin --- bicistronic --- HCV --- HIV --- IL-36 --- adjuvant --- DNA --- Zika --- Epstein-Barr virus --- latent proteins --- LMP2 --- EBNA1 --- LMP1 --- HIV-1 --- enhancer element --- circovirus --- influenza --- immunization --- intranasal --- lipid --- flagellin --- BCG --- vaccine --- rBCG --- HTI --- T-cell --- AIDS --- clinical trial --- therapeutic vaccine --- hepatitis C virus (HCV) --- mesenchymal stem cells (MSC) --- modified MSC --- DNA immunization --- nonstructural HCV proteins --- immune response --- HCV vaccine --- myeloid derived suppressor cells (MDSCs) --- n/a