Journal articles: 'Antigen delivery'

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Jiang, Jizong. "Cell-penetrating Peptide-mediated Nanovaccine Delivery." Current Drug Targets 22, no. 8 (June 1, 2021): 896–912. http://dx.doi.org/10.2174/1389450122666210203193225.

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Vaccination with small antigens, such as proteins, peptides, or nucleic acids, is used to activate the immune system and trigger the protective immune responses against a pathogen. Currently, nanovaccines are undergoing development instead of conventional vaccines. The size of nanovaccines is in the range of 10-500 nm, which enables them to be readily taken up by cells and exhibit improved safety profiles. However, low-level immune responses, as the removal of redundant pathogens, trigger counter-effective activation of the immune system invalidly and present a challenging obstacle to antigen recognition and its uptake via antigen-presenting cells (APCs). In addition, toxicity can be substantial. To overcome these problems, a variety of cell-penetrating peptide (CPP)-mediated vaccine delivery systems based on nanotechnology have been proposed, most of which are designed to improve the stability of antigens in vivo and their delivery into immune cells. CPPs are particularly attractive components of antigen delivery. Thus, the unique translocation property of CPPs ensures that they remain an attractive carrier with the capacity to deliver cargo in an efficient manner for the application of drugs, gene transfer, protein, and DNA/RNA vaccination delivery. CPP-mediated nanovaccines can enhance antigen uptake, processing, and presentation by APCs, which are the fundamental steps in initiating an immune response. This review describes the different types of CPP-based nanovaccines delivery strategies.

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Kersten, Gideon, and Hoang Hirschberg. "Antigen delivery systems." Expert Review of Vaccines 3, no. 4 (August 2004): 453–62. http://dx.doi.org/10.1586/14760584.3.4.453.

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Sinclair, Meeghan. "Improving antigen delivery." Nature Biotechnology 18, no. 9 (September 2000): 915. http://dx.doi.org/10.1038/79364.

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Bungener, Laura, Anke Huckriede, Jan Wilschut, and Toos Daemen. "Delivery of Protein Antigens to the Immune System by Fusion-Active Virosomes: A Comparison with Liposomes and ISCOMs." Bioscience Reports 22, no. 2 (April 1, 2002): 323–38. http://dx.doi.org/10.1023/a:1020198908574.

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The induction of effective cellular and humoral immune responses against protein antigens is of major importance in vaccination strategies against infectious diseases and cancer. Immunization with protein alone in general does not result in efficient induction of cytotoxic T lymphocyte (CTL) and antibody responses. Numerous other immunization strategies have been explored. In this review we will discuss a number of lipid-based antigen delivery systems suitable for the induction of CTL responses. These systems comprise reconstituted virus envelopes (virosomes), liposomes, and immune-stimulating complexes (ISCOMs). We will concentrate on delivery of the protein antigen ovalbumin (OVA) since extensive studies with this antigen have been performed for all of the systems discussed, allowing direct comparison of antigen delivery efficiency. Stimulation of CTL activity requires processing of the antigen in the cytosol of antigen-presenting cells (APCs) and presentation of antigenic peptides on surface major histocompatibility class I complexes (MHC class I). In vitro, the ability of antigen delivery systems to induce MHC class I presentation indeed correlates with their capacity to deliver antigen to the cytosol of cells. This capacity appears to be less important for the induction of cytotoxic T lymphocytes in vivo. Instead, other properties of the antigen delivery system like activation of APCs and induction of T helper cells play a more prominent role. Fusion-active virosomes appear to be a very potent system for induction of CTL activity, most likely since virosomes combine efficient delivery of antigen with general stimulation of the immune system.

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Shaw, Christine A., and Michael N. Starnbach. "Stimulation of CD8+ T Cells following Diphtheria Toxin-Mediated Antigen Delivery into Dendritic Cells." Infection and Immunity 74, no. 2 (February 2006): 1001–8. http://dx.doi.org/10.1128/iai.74.2.1001-1008.2006.

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ABSTRACT Recognition and clearance of many intracellular pathogens requires the activation and subsequent effector functions of CD8+ T lymphocytes. To stimulate CD8+ T cells by immunization, the target antigens must be delivered into the cytosol of host cells. There they can be processed into peptides and presented in the context of major histocompatibility complex class I molecules to antigen-specific CD8+ T cells. One method of delivering antigens into the cytosol is to fuse them to modified bacterial toxins that are able to enter mammalian cells. The expression pattern of the toxin receptors in the host will determine the cell population that the toxin fusion protein targets and will thus restrict antigen-specific T-cell recognition to the same population. In this study we describe the development and characterization of a diphtheria toxin (DT)-based antigen delivery system. Using CD11c-DTR transgenic mice that express the DT receptor in dendritic cells (DC), this system allows for targeted delivery of CD8+ T-cell antigen to DC. We show that antigen-specific CD8+ T cells proliferate in CD11c-DTR mice following immunization with catalytically inactive DT-antigen fusion proteins. We also show that a toxin-based system that restricts antigen delivery to DC results in more robust antigen-specific CD8+ T-cell proliferation than a toxin-based system that does not restrict delivery to a particular cell type. These results have implications for vaccine design, and they suggest that use of a toxin-based vector to target antigen to DC may be an effective way to induce a CD8+ T-cell response.

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Maloney, Michael, Scott Loughhead, Amritha Ramakrishnan, Carolyne Smith, Anita Venkitaraman, Christian Yee, Miye Jacques, et al. "169 Microfluidics cell squeezing enables human PBMCs as drivers of antigen-specific CD8 T responses across broad range of antigens for diverse clinical applications." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (November 2020): A183. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0169.

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BackgroundAntigen-specific CD8+ T cell activity is critical for mounting an effective immune response in a wide range of indications, including immune-oncology and infectious diseases.MethodsTo elicit antigen-specific CD8+ T cell activity, we used microfluidics cell squeezing (Cell Squeeze®) to deliver antigens directly to the cytosol of antigen presenting cells (APCs). Direct cytosolic delivery bypasses the need for cross-presentation and efficiently loads antigen into the major histocompatibility complex class I (MHC-I) pathway. The Cell Squeeze® platform is generally agnostic to cell type and material. Therefore, not only does microfluidic squeezing enable cell subsets within human peripheral blood mononuclear cells (PBMCs) to function as unconventional APCs, but it also enables us to efficiently investigate a wide range of antigens including whole protein, peptides, and mRNA. This ‘plug and play’ nature of the platform allows for broad application in multiple disease areas.ResultsIn human cells, we demonstrated that microfluidic squeezing of PBMCs enables effective delivery to the major cell subsets including T cells, B cells, NK cells and monocytes. Delivery of CMV and HPV16 synthetic long peptides (SLPs) resulted in robust in vitro responses of both CD8+ T cell clones and patient-derived memory populations. To broaden the impact of our PBMC-based cell therapy approach, we investigated several other antigens relevant to other disease areas. Additional materials we delivered via squeezing and demonstrated antigen presentation include neoantigens, M1 Influenza mRNA, and pp65 SLP. Cell Squeeze® platform is simple to use and amenable to scale up. We demonstrated that delivery and viability for research scale process (~2 × 106 cells) is equivalent to delivery and viability of PBMCs processed at manufacturing scale (~1 × 109 cells).ConclusionsMicrofluidic cell squeezing of human PBMCs with antigenic material can be tailored to produce APCs that drive robust CD8+ T cell response against targets across multiple disease areas and has been scaled up for clinical use. SQZ-PBMC-HPV are currently under clinical evaluation for treatment of HPV16+ tumors.

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Rainczuk, A., T. Scorza, T. W. Spithill, and P. M. Smooker. "A Bicistronic DNA Vaccine Containing Apical Membrane Antigen 1 and Merozoite Surface Protein 4/5 Can Prime Humoral and Cellular Immune Responses and Partially Protect Mice against Virulent Plasmodium chabaudi adami DS Malaria." Infection and Immunity 72, no. 10 (October 2004): 5565–73. http://dx.doi.org/10.1128/iai.72.10.5565-5573.2004.

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ABSTRACT The ultimate malaria vaccine will require the delivery of multiple antigens from different stages of the complex malaria life cycle. In order to efficiently deliver multiple antigens with use of DNA vaccine technology, new antigen delivery systems must be assessed. This study utilized a bicistronic vector construct, containing an internal ribosome entry site, expressing a combination of malarial candidate antigens: merozoite surface protein 4/5 (MSP4/5) (fused to a monocyte chemotactic protein 3 chemoattractant sequence) and apical membrane antigen 1 (AMA-1) (fused to a tissue plasminogen activator secretion signal). Transfection of COS 7 cells with bicistronic plasmids resulted in production and secretion of both AMA-1 and MSP4/5 in vitro. Vaccination of BALB/c mice via intraepidermal gene gun and intramuscular routes against AMA-1 and MSP4/5 resulted in antibody production and significant in vitro proliferation of splenocytes stimulated by both AMA-1 and MSP4/5. Survival of BALB/c mice vaccinated with bicistronic constructs after lethal Plasmodium chabaudi adami DS erythrocytic-stage challenge was variable, although significant increases in survival and reductions in peak parasitemia were observed in several challenge trials when the vaccine was delivered by the intramuscular route. This study using a murine model demonstrates that the delivery of malarial antigens via bicistronic vectors is feasible. Further experimentation with bicistronic delivery systems is required for the optimization and refinement of DNA vaccines to effectively prime protective immune responses against malaria.

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Munang’andu, Hetron Mweemba, and Øystein Evensen. "A Review of Intra- and Extracellular Antigen Delivery Systems for Virus Vaccines of Finfish." Journal of Immunology Research 2015 (2015): 1–19. http://dx.doi.org/10.1155/2015/960859.

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Vaccine efficacy in aquaculture has for a long time depended on evaluating relative percent survival and antibody responses after vaccination. However, current advances in vaccine immunology show that the route in which antigens are delivered into cells is deterministic of the type of adaptive immune response evoked by vaccination. Antigens delivered by the intracellular route induce MHC-I restricted CD8+ responses while antigens presented through the extracellular route activate MHC-II restricted CD4+ responses implying that the route of antigen delivery is a conduit to induction of B- or T-cell immune responses. In finfish, different antigen delivery systems have been explored that include live, DNA, inactivated whole virus, fusion protein, virus-like particles, and subunit vaccines although mechanisms linking these delivery systems to protective immunity have not been studied in detail. Hence, in this review we provide a synopsis of different strategies used to administer viral antigens via the intra- or extracellular compartments. Further, we highlight the differences in immune responses induced by antigens processed by the endogenous route compared to exogenously processed antigens. Overall, we anticipate that the synopsis put together in this review will shed insights into limitations and successes of the current vaccination strategies used in finfish vaccinology.

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Cohen, Smadar, Maria J. Alonso, and Robert Langer. "Novel Approaches to Controlled-Release Antigen Delivery." International Journal of Technology Assessment in Health Care 10, no. 1 (1994): 121–30. http://dx.doi.org/10.1017/s0266462300014045.

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AbstractTwo strategies for vaccine-delivery systems, both relying on concepts of controlled-release technology, are described in this review. The first strategy involves using biodegradable polymer microspheres for parenteral and oral delivery of antigens. The other strategy combines two technologies, the encapsulation of antigen within liposomes and liposome encapsulation in hydrogels, to protect them from a rapid degradation in vivo. Both strategies have shown promise in terms of increasing the immunogenicity of poorly immunogenic peptides and protein vaccines. The microencapsulation process, antigen stability, mechanism of antigen release, and optimal release kinetics for vaccine delivery are reviewed, and the strengths and weaknesses of each approach are discussed.

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Lee, Mi-Young, Meong-Cheol Shin, and Victor C. Yang. "Transcutaneous antigen delivery system." BMB Reports 46, no. 1 (January 31, 2013): 17–24. http://dx.doi.org/10.5483/bmbrep.2013.46.1.001.

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Wengerter, Brian C., Joseph A. Katakowski, Jacob M. Rosenberg, Chae Gyu Park, Steven C. Almo, Deborah Palliser, and Matthew Levy. "Aptamer-targeted Antigen Delivery." Molecular Therapy 22, no. 7 (July 2014): 1375–87. http://dx.doi.org/10.1038/mt.2014.51.

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Trovato, Maria. "Novel antigen delivery systems." World Journal of Virology 4, no. 3 (2015): 156. http://dx.doi.org/10.5501/wjv.v4.i3.156.

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Konjufca, Vjollca, Mark Jenkins, Shifeng Wang, Maria Dolores Juarez-Rodriguez, and Roy Curtiss. "Immunogenicity of Recombinant Attenuated Salmonella enterica Serovar Typhimurium Vaccine Strains Carrying a Gene That Encodes Eimeria tenella Antigen SO7." Infection and Immunity 76, no. 12 (September 22, 2008): 5745–53. http://dx.doi.org/10.1128/iai.00897-08.

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ABSTRACT Recombinant attenuated Salmonella vaccines against avian coccidiosis were developed to deliver Eimeria species antigens to the lymphoid tissues of chickens via the type 3 secretion system (T3SS) and the type 2 secretion system (T2SS) of Salmonella. For antigen delivery via the T3SS, the Eimeria tenella gene encoding sporozoite antigen SO7 was cloned downstream of the translocation domain of the Salmonella enterica serovar Typhimurium sopE gene in the parental pYA3868 and pYA3870 vectors to generate pYA4156 and pYA4157. Newly constructed T3SS vectors were introduced into host strain χ8879 (ΔphoP233 ΔsptP1033::xylE ΔasdA16), an attenuated derivative of the highly virulent UK-1 strain. The SopE-SO7 fusion protein was secreted by the T3SS of Salmonella. The vector pYA4184 was constructed for delivery of the SO7 antigen via the T2SS. The SO7 protein was toxic to Salmonella when larger amounts were synthesized; thus, the synthesis of this protein was placed under the control of the lacI repressor gene, whose expression in turn was dependent on the amount of available arabinose in the medium. The pYA4184 vector was introduced into host strain χ9242 (ΔphoP233 ΔasdA16 ΔaraBAD23 ΔrelA198::araC PBAD lacI TT [TT is the T4ipIII transcription terminator]). In addition to SO7, for immunization and challenge studies we used the EAMZ250 antigen of Eimeria acervulina, which was previously shown to confer partial protection against E. acervulina challenge when it was delivered via the T3SS. Immunization of chickens with a combination of the SO7 and EAMZ250 antigens delivered via the T3SS induced superior protection against challenge by E. acervulina. In contrast, chickens immunized with SO7 that was delivered via the T2SS of Salmonella were better protected from challenge by E. tenella.

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Zhang, Hongxia, Xinru You, Xiaojuan Wang, Lei Cui, Zining Wang, Feifei Xu, Mengyun Li, et al. "Delivery of mRNA vaccine with a lipid-like material potentiates antitumor efficacy through Toll-like receptor 4 signaling." Proceedings of the National Academy of Sciences 118, no. 6 (February 5, 2021): e2005191118. http://dx.doi.org/10.1073/pnas.2005191118.

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Intracellular delivery of messenger RNA (mRNA)-based cancer vaccine has shown great potential to elicit antitumor immunity. To achieve robust antitumor efficacy, mRNA encoding tumor antigens needs to be efficiently delivered and translated in dendritic cells with concurrent innate immune stimulation to promote antigen presentation. Here, by screening a group of cationic lipid-like materials, we developed a minimalist nanovaccine with C1 lipid nanoparticle (LNP) that could efficiently deliver mRNA in antigen presenting cells with simultaneous Toll-like receptor 4 (TLR4) activation and induced robust T cell activation. The C1 nanovaccine entered cells via phagocytosis and showed efficient mRNA-encoded antigen expression and presentation. Furthermore, the C1 lipid nanoparticle itself induced the expression of inflammatory cytokines such as IL-12 via stimulating TLR4 signal pathway in dendritic cells. Importantly, the C1 mRNA nanovaccine exhibited significant antitumor efficacy in both tumor prevention and therapeutic vaccine settings. Overall, our work presents a C1 LNP-based mRNA cancer nanovaccine with efficient antigen expression as well as self-adjuvant property, which may provide a platform for developing cancer immunotherapy for a wide range of tumor types.

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Bradley, Mark P., Lyn A. Hinds, and Peter H. Bird. "A bait-delivered immunocontraceptive vaccine for the European red fox (Vulpes vulpes) by the year 2002?" Reproduction, Fertility and Development 9, no. 1 (1997): 111. http://dx.doi.org/10.1071/r96066.

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An orally-delivered immunocontraceptive vaccine is being developed for the control of fox populations. A number of genes (PH-20, LDH-C4, ZP3) encoding gamete proteins have been cloned, produced in recombinant expression systems and used in fertility trials to test the efficacy of these antigens. As the immunocontraceptive vaccine will be delivered in a bait, there is a requirement for a greater understanding of the immune responses of the reproductive mucosa in canids, and the assessment of the best vaccine delivery system that will evoke a mucosal antibody response. Several vaccine delivery systems including microencapsulated antigens, and both vaccinia virus and bacterial vectors are being investigated. Oral administration of Salmonella typhimurium recombinants expressing different fox sperm antigens stimulates both systemic IgG responses to the antigen and a mucosal immune response within the female reproductive tract in the fox, indicating that salmonella may have potential with respect to the oral delivery of antigen. The enhancement of mucosal immune responses to orally-delivered vaccines is also being examined, research focussing on the possible use of fox-specific cytokines or the β-subunit of cholera toxin in forming part of the vaccine construct.

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Shaw, Christine A., and Michael N. Starnbach. "Both CD4+ and CD8+ T Cells Respond to Antigens Fused to Anthrax Lethal Toxin." Infection and Immunity 76, no. 6 (March 17, 2008): 2603–11. http://dx.doi.org/10.1128/iai.01718-07.

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ABSTRACT The lethal toxin produced by Bacillus anthracis is a bipartite toxin in which the first protein, protective antigen (PA), transports the second protein, lethal factor, across the host cell membrane. We have previously shown that CD8+ T-cell epitopes fused to a nontoxic derivative of lethal factor (LFn) are delivered into the host cell cytosol in a PA-dependent manner. Delivery of these antigens targets them to the intracellular major histocompatibility complex (MHC) class I processing and presentation pathway and leads to the stimulation of antigen-specific CD8+ T cells in vivo. In this report, we describe the generation and characterization of LFn fusion proteins that include not only a CD8+ T-cell epitope but also a CD4+ T-cell epitope. We first show that these fusion proteins induce antigen-specific CD4+ T-cell responses following incubation with dendritic cells in vitro or injection into mice. Stimulation of CD4+ T cells by LFn fusion proteins does not require PA but is enhanced by PA in vitro. We also show that a single LFn fusion protein and PA can deliver antigen to both the MHC class II and the MHC class I pathways, resulting in the simultaneous induction of antigen-specific CD4+ T cells and antigen-specific CD8+ T cells in the same mouse. These results suggest that this toxin delivery system is capable of stimulating protective immune responses where effective immunization requires stimulation of both classes of T cells.

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Shim, Soojin, and Han Sang Yoo. "The Application of Mucoadhesive Chitosan Nanoparticles in Nasal Drug Delivery." Marine Drugs 18, no. 12 (November 29, 2020): 605. http://dx.doi.org/10.3390/md18120605.

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Mucosal delivery of antigens can induce both humoral and cellular immune responses. Particularly, the nasal cavity is a strongly inductive site for mucosal immunity among several administration routes, as it is generally the first point of contact for inhaled antigens. However, the delivery of antigens to the nasal cavity has some disadvantages such as rapid clearance and disposition of inhaled materials. For these reasons, remarkable efforts have been made to develop antigen delivery systems which suit the nasal route. The use of nanoparticles as delivery vehicles enables protection of the antigen from degradation and sustains the release of the loaded antigen, eventually resulting in improved vaccine and/or drug efficacy. Chitosan, which exhibits low toxicity, biodegradability, good cost performance, and strong mucoadhesive properties, is a useful material for nanoparticles. The present review provides an overview of the mucosal immune response induced by nanoparticles, recent advances in the use of nanoparticles, and nasal delivery systems with chitosan nanoparticles.

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Loeffler, Daniela I. M., Christoph U. Schoen, Werner Goebel, and Sabine Pilgrim. "Comparison of Different Live Vaccine Strategies In Vivo for Delivery of Protein Antigen or Antigen-Encoding DNA and mRNA by Virulence-Attenuated Listeria monocytogenes." Infection and Immunity 74, no. 7 (July 2006): 3946–57. http://dx.doi.org/10.1128/iai.00112-06.

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ABSTRACT Listeria monocytogenes can be used to deliver protein antigens or DNA and mRNA encoding such antigens directly into the cytosol of host cells because of its intracellular lifestyle. In this study, we compare the in vivo efficiencies of activation of antigen-specific CD8 and CD4 T cells when the antigen is secreted by L. monocytogenes or when antigen-encoding plasmid DNA or mRNA is released by self-destructing strains of L. monocytogenes. Infection of mice with self-destructing L. monocytogenes carriers delivering mRNA that encodes a nonsecreted form of ovalbumin (OVA) resulted in a significant OVA-specific CD8 T-cell response. In contrast, infection with L. monocytogenes delivering OVA-encoding DNA failed to generate specific T cells. Secretion of OVA by the carrier bacteria yielded the strongest immune response involving OVA-specific CD8 and CD4 T cells. In addition, we investigated the antigen delivery capacity of a self-destructing, virulence-attenuated L. monocytogenes aroA/B mutant. In contrast to the wild-type strain, this mutant exhibited only marginal liver toxicity when high doses (5 × 107 CFU per animal administered intravenously) were used, and it was also able to deliver sufficient amounts of secreted OVA into mice. Therefore, the results presented here could lay the groundwork for a rational combination of L. monocytogenes as an attenuated carrier for the delivery of protein and nucleic acid vaccines in novel vaccination strategies.

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Chikh, Ghania, and Marie-Paule Schutze-Redelmeir. "Liposomal Delivery of CTL Epitopes to Dendritic Cells." Bioscience Reports 22, no. 2 (April 1, 2002): 339–53. http://dx.doi.org/10.1023/a:1020151025412.

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The induction of strong and long lasting T-cell response, CD4+ or CD8+, is a major requirement in the development of efficient vaccines. An important aspect involves delivery of antigens to dendritic cells (DCs) as antigen presenting cells (APCs) for the induction of potent antigen-specific CD8+ T lymphocyte (CTLs) responses. Protein or peptide-based vaccines become an attractive alternative to the use of live cell vaccines to stimulate CTL responses for the treatment of viral diseases or malignancies. However, vaccination with proteins or synthetic peptides representing discrete CTL epitopes have failed in most instances due to the inability for exogenous antigens to be properly presented to T cells via major histocompatibility complex (MHC) class I molecules. Modern vaccines, based on either synthetic or natural molecules, will be designed in order to target appropriately professional APCs and to co-deliver signals able to facilitate activation of DCs. In this review, we describe the recent findings in the development of lipid-based formulations containing a combination of these attributes able to deliver tumor- or viral-associated antigens to the cytosol of DCs. We present in vitro and pre-clinical studies reporting specific immunity to viral, parasitic infection and tumor growth.

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Wi, Tae In, Yeongseon Byeon, Ji Eun Won, Jae Myeong Lee, Tae Heung Kang, Jeong-Won Lee, Young Joo Lee, Anil K. Sood, Hee Dong Han, and Yeong-Min Park. "Selective Tumor-Specific Antigen Delivery to Dendritic Cells Using Mannose-Labeled Poly(d, l-lactide-co-glycolide) Nanoparticles for Cancer Immunotherapy." Journal of Biomedical Nanotechnology 16, no. 2 (February 1, 2020): 201–11. http://dx.doi.org/10.1166/jbn.2020.2883.

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A key issue in dendritic cell (DC)-based cancer immunotherapy is the effective delivery of tumor-specific antigens to DCs. To deliver antigens, non-viral vaccine system has been used in ex vivo manipulation. However, ex vivo manipulation is time-consuming, lacks quality control of DCs, and demonstrates low antigen delivery efficiency, which implicates that there are serious problems in therapeutic DC preparations. Therefore, we developed mannose (MN)-labeled poly(d, l-lactide-co-glycolide) (PLGA) nanoparticles (MN-PLGA-NPs) encapsulating tumor-specific antigens for targeted delivery to mannose receptors (MN-R) on DC surfaces without ex vivo manipulation. The MN-PLGA-NPs showed DC-selective delivery in tumor-bearing mice, leading to highly mature and activated DCs, which migrated to lymphoid organs, resulting in activation of cytotoxic CD8+ T cells. Additionally, MN-PLGA-NPs showed significant therapeutic efficacy in EG7 lymphoma tumorbearing mice. Our nano-platform technology can be used as a vaccine system to bypass ex vivo manipulation and enhance targeted delivery of tumor-specific antigens to DCs, which is well-suited for cancer immunotherapy.

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Grenfell, Rafaella F. Q., Lisa M. Shollenberger, E. Farah Samli, and Donald A. Harn. "Vaccine Self-Assembling Immune Matrix Is a New Delivery Platform That Enhances Immune Responses to Recombinant HBsAg in Mice." Clinical and Vaccine Immunology 22, no. 3 (January 21, 2015): 336–43. http://dx.doi.org/10.1128/cvi.00714-14.

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ABSTRACTVaccination remains the most effective public health tool to prevent infectious diseases. Many vaccines are marginally effective and need enhancement for immunocompromised, elderly, and very young populations. To enhance immunogenicity, we exploited the biphasic property of the (RADA)4 synthetic oligopeptide to create VacSIM (vaccine self-assembling immune matrix), a new delivery method. VacSIM solution can easily be mixed with antigens, organisms, and adjuvants for injection. Postinjection, the peptides self-assemble into hydrated nanofiber gel matrices, forming a depot with antigens and adjuvants in the aqueous phase. We believe the depot provides slow release of immunogens, leading to increased activation of antigen-presenting cells that then drive enhanced immunogenicity. Using recombinant hepatitis B virus surface antigen (rHBsAg) as a model immunogen, we compared VacSIM delivery to delivery in alum or complete Freund's adjuvant (CFA). Delivery of the rHBsAg antigen to mice via VacSIM without adjuvant elicited higher specific IgG responses than when rHBsAg was delivered in alum or CFA. Evaluating IgG subtypes showed a mixed Th1/Th2 type response following immunization with VacSIM, which was driven further toward Th1 with addition of CpG as the adjuvant. Increased specific IgG endpoint titers were observed in both C57BL/6 and BALB/c mice, representative of Th1 and Th2 environments, respectively. Restimulation of splenocytes suggests that VacSIM does not cause an immediate proinflammatory response in the host. Overall, these results suggest that VacSIM, as a new delivery method, has the potential to enhance immunogenicity and efficacy of numerous vaccines.

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Igwe, Emeka I., Gernot Geginat, and Holger Rüssmann. "Concomitant Cytosolic Delivery of Two Immunodominant Listerial Antigens by Salmonella enterica Serovar Typhimurium Confers Superior Protection against Murine Listeriosis." Infection and Immunity 70, no. 12 (December 2002): 7114–19. http://dx.doi.org/10.1128/iai.70.12.7114-7119.2002.

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ABSTRACT During its interaction with host cells, Salmonella enterica serovar Typhimurium employs a type III secretion system for cytosolic targeting of virulence factors. This protein translocation mechanism is a useful tool for heterologous antigen delivery by attenuated Salmonella vaccine carrier strains. In the present study, we used the Yersinia outer protein E (YopE) as a carrier molecule for Salmonella type III-dependent cytosolic delivery of the immunodominant CD8 T-cell antigens listeriolysin O (LLO) and p60 of Listeria monocytogenes. It is shown that concomitant translocation of hybrid YopE/LLO and YopE/p60 proteins by Salmonella led to antigen presentation and CD8 T-cell priming efficacies comparable to those of translocation of single listerial antigens. However, simultaneous translocation of LLO and p60 significantly surpassed single cytosolic antigen delivery in the ability to protect against Listeria. For the first time, this study demonstrates that concomitant expression of two independent antigens via the same recombinant plasmid leads to superior protection against a challenge with an intracellular bacterial pathogen. In conclusion, these findings emphasize the versatility of Salmonella type III-mediated heterologous antigen delivery for the induction of cytotoxic T-lymphocyte-mediated immunity.

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de Haan, Lolke, Arron R. Hearn, A. Jennifer Rivett, and Timothy R. Hirst. "Enhanced Delivery of Exogenous Peptides into the Class I Antigen Processing and Presentation Pathway." Infection and Immunity 70, no. 6 (June 2002): 3249–58. http://dx.doi.org/10.1128/iai.70.6.3249-3258.2002.

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ABSTRACT Current immunization strategies, using peptide or protein antigens, generally fail to elicit cytotoxic-T-lymphocyte responses, since these antigens are unable to access intracellular compartments where loading of major histocompatibility complex class I (MHC-I) molecules occurs. In an attempt to circumvent this, we investigated whether the GM1 receptor-binding B subunit of Escherichia coli heat-labile toxin (EtxB) could be used to deliver class I epitopes. When a class I epitope was conjugated to EtxB, it was delivered into the MHC-I presentation pathway in a GM1-binding-dependent fashion and resulted in the appearance of MHC-I-epitope complexes at the cell surface. Importantly, we show that the efficiency of EtxB-mediated epitope delivery could be strikingly enhanced by incorporating, adjacent to the class I epitope, a 10-amino-acid segment from the C terminus of the DNA polymerase (Pol) of herpes simplex virus. The replacement of this 10-amino-acid segment by a heterologous sequence or the introduction of specific amino acid substitutions within this segment either abolished or markedly reduced the efficiency of class I epitope delivery. If the epitope was extended at its C terminus, EtxB-mediated delivery into the class I presentation pathway was found to be completely dependent on proteasome activity. Thus, by combining the GM1-targeting function of EtxB with the 10-amino-acid Pol segment, highly efficient delivery of exogenous epitopes into the endogenous pathway of class I antigen processing and presentation can be achieved.

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Moser, Christian, Ian C. Metcalfe, and Jean-François Viret. "Virosomal adjuvanted antigen delivery systems." Expert Review of Vaccines 2, no. 2 (April 2003): 189–96. http://dx.doi.org/10.1586/14760584.2.2.189.

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FitzGerald, David, and Randall J. Mrsny. "New Approaches to Antigen Delivery." Critical Reviews in Therapeutic Drug Carrier Systems 17, no. 3 (2000): 84. http://dx.doi.org/10.1615/critrevtherdrugcarriersyst.v17.i3.10.

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Gonzalez-Aramundiz, Jose Vicente, Ana Sara Cordeiro, Nœmi Csaba, Maria de la Fuente, and María José Alonso. "Nanovaccines : nanocarriers for antigen delivery." Biologie Aujourd'hui 206, no. 4 (2012): 249–61. http://dx.doi.org/10.1051/jbio/2012027.

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Schijns, Virgil E. J. C. "Antigen delivery systems and immunostimulation." Veterinary Immunology and Immunopathology 87, no. 3-4 (September 2002): 195–98. http://dx.doi.org/10.1016/s0165-2427(02)00072-7.

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OʼHagan, Derek T. "Novel nonreplicating antigen delivery systems." Current Opinion in Infectious Diseases 3, no. 3 (June 1990): 393–401. http://dx.doi.org/10.1097/00001432-199006000-00013.

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Park, Joo Yeon, Mi-Gyeong Kim, Gayong Shim, and Yu-Kyoung Oh. "Lipid-based antigen delivery systems." Journal of Pharmaceutical Investigation 46, no. 4 (April 18, 2016): 295–304. http://dx.doi.org/10.1007/s40005-016-0246-z.

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Garbi, Natalio, and Christian Kurts. "The Hierarchy of Antigen Delivery." EBioMedicine 5 (March 2016): 7–8. http://dx.doi.org/10.1016/j.ebiom.2016.02.031.

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PEARSE, M., and D. DRANE. "ISCOMATRIX� adjuvant for antigen delivery." Advanced Drug Delivery Reviews 57, no. 3 (January 10, 2005): 465–74. http://dx.doi.org/10.1016/j.addr.2004.09.006.

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Moll, Heidrun. "Antigen delivery by dendritic cells." International Journal of Medical Microbiology 294, no. 5 (October 2004): 337–44. http://dx.doi.org/10.1016/j.ijmm.2004.03.003.

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Hirst, Timothy R. "Non-living antigen delivery systems." Vaccine 10, no. 4 (January 1992): 265. http://dx.doi.org/10.1016/0264-410x(92)90179-n.

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Han, Xiao, Shufang Shen, Qin Fan, Guojun Chen, Edikan Archibong, Gianpietro Dotti, Zhuang Liu, Zhen Gu, and Chao Wang. "Red blood cell–derived nanoerythrosome for antigen delivery with enhanced cancer immunotherapy." Science Advances 5, no. 10 (October 2019): eaaw6870. http://dx.doi.org/10.1126/sciadv.aaw6870.

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Erythrocytes or red blood cells (RBCs) represent a promising cell-mediated drug delivery platform due to their inherent biocompatibility. Here, we developed an antigen delivery system based on the nanoerythrosomes derived from RBCs, inspired by the splenic antigen-presenting cell targeting capacity of senescent RBCs. Tumor antigens were loaded onto the nanoerythrosomes by fusing tumor cell membrane–associated antigens with nanoerythrosomes. This tumor antigen–loaded nanoerythrosomes (nano-Ag@erythrosome) elicited antigen responses in vivo and, in combination with the anti–programmed death ligand 1 (PD-L1) blockade, inhibited the tumor growth in B16F10 and 4T1 tumor models. We also generated a tumor model showing that “personalized nano-Ag@erythrosomes” could be achieved by fusing RBCs and surgically removed tumors, which effectively reduced tumor recurrence and metastasis after surgery.

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Vangala, Anil, Vincent W. Bramwell, Sarah McNeil, Dennis Christensen, Else Marie Agger, and Yvonne Perrie. "Comparison of vesicle based antigen delivery systems for delivery of hepatitis B surface antigen." Journal of Controlled Release 119, no. 1 (May 2007): 102–10. http://dx.doi.org/10.1016/j.jconrel.2007.01.010.

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KNOX, D. P. "Development of vaccines against gastrointestinal nematodes." Parasitology 120, no. 7 (May 2000): 43–61. http://dx.doi.org/10.1017/s0031182099005764.

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Vaccination against complex metazoan parasites has become a reality with the development and registration of recombinant protein-based vaccines against the cattle tick Boophilus microplus and the sheep cestode Taenia ovis. Progress towards the development of similar vaccines against gastrointestinal nematodes, primarily of ruminants, is outlined within a framework of defining the practical requirements for successful vaccination, antigen selection, recombinant protein production and antigen delivery, be it mucosal delivery or DNA vaccination. Antigen selection strategies include the fractionation of complex, but protective, parasite extracts, the use of antibody probes, evaluation of excretory-secretory components and gut-expressed hidden antigens as well as antigens targeted on the basis of function such as enzyme activity. The difficulties being encountered in recombinant protein production and their solution are discussed as are the requirements for successful antigen delivery. Recent technological developments such as the use of functional genomics to identify new vaccine candidates and DNA vaccination to present the selected antigen to the host immune system are discussed and are anticipated to have a profound effect on vaccine development in the future.

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Yazdani, Mona, Mahmoud Reza Jaafari, Javad Verdi, Behrang Alani, Mahdi Noureddini, and Ali Badiee. "Ex vivo-generated dendritic cell-based vaccines in melanoma: the role of nanoparticulate delivery systems." Immunotherapy 12, no. 5 (April 2020): 333–49. http://dx.doi.org/10.2217/imt-2019-0173.

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Melanoma is a poor immunogenic cancer and many treatment strategies have been used to enhance specific or nonspecific immunity against it. Dendritic cell (DC)-based cancer vaccine is the most effective therapies that have been used so far. Meanwhile, the efficacy of DC-based immunotherapy relies on critical factors relating to DCs such as the state of maturation and proper delivery of antigens. In this regard, the use of nanoparticulate delivery systems for effective delivery of antigen to ex vivo-generated DC-based vaccines that also poses adjuvanticity would be an ideal approach. In this review article, we attempt to summarize the role of different types of nanoparticulate antigen delivery systems used in the development of ex vivo-generated DC-based vaccines against melanoma and describe their adjuvanticity in mediation of DC maturation, cytoplasmic presentation of antigens to MHC class I molecules, which led to potent antigen-specific immune responses. As were represented, cationic liposomes were the most used approach, which suggest its potential applicability as delivery systems for further experiments in combination with either adjuvants or monoclonal antibodies.

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Connell, Tom G., Muki S. Shey, Ronnett Seldon, Molebogeng X. Rangaka, Gilles van Cutsem, Marcela Simsova, Zuzana Marcekova, et al. "Enhanced Ex Vivo Stimulation of Mycobacterium tuberculosis-Specific T Cells in Human Immunodeficiency Virus-Infected Persons via Antigen Delivery by the Bordetella pertussis Adenylate Cyclase Vector." Clinical and Vaccine Immunology 14, no. 7 (May 23, 2007): 847–54. http://dx.doi.org/10.1128/cvi.00041-07.

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ABSTRACTThe genetically detoxifiedBordetella pertussisadenylate cyclase is a promising delivery system for immunodominant tuberculosis antigens in gamma interferon release assays. This system has not been evaluated in human immunodeficiency virus (HIV)-infected persons in high tuberculosis prevalence areas. A whole-blood gamma interferon release assay withMycobacterium tuberculosisantigens (early-secreted antigenic target 6, culture filtrate protein 10, alpha-crystallin 2, and TB10.3) delivered by adenylate cyclase in addition to native tuberculosis antigens (without adenylate cyclase delivery) was evaluated in 119 adults in Khayelitsha Township, Cape Town, South Africa. Results were compared to tuberculin skin test results of 41 HIV-positive and 42 HIV-negative asymptomatic persons, in addition to 36 HIV-positive persons with recently diagnosed smear- or culture-positive pulmonary tuberculosis. Delivery of tuberculosis antigens by adenylate cyclase decreased by 10-fold the amount of antigen required to restimulate T cells. Furthermore, the responses of HIV-positive persons with a low response to native tuberculosis antigens were enhanced when these antigens were delivered by adenylate cyclase. When gamma interferon responses to the tuberculosis antigens (with or without delivery by adenylate cyclase) were combined, a significantly higher number of patients were scored positive than by tuberculin skin testing. Ex vivo responses to tuberculosis antigens delivered by adenylate cyclase are maintained in the context of HIV infection. Our findings suggest that the majority of those in this population are infected with tuberculosis, which is of significant public health importance.

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kheirollahpour, Mehdi, Mohsen Mehrabi, Naser Mohammadpour Dounighi, Mohsen Mohammadi, and Alireza Masoudi. "Nanoparticles and Vaccine Development." Pharmaceutical Nanotechnology 8, no. 1 (February 6, 2020): 6–21. http://dx.doi.org/10.2174/2211738507666191024162042.

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In spite of the progress of conventional vaccines, improvements are required due to concerns about the low immunogenicity of the toxicity, instability, and the need for multiple administrations of the vaccines. To overcome the mentioned problems, nanotechnology has recently been incorporated into vaccine development. Nanotechnology increasingly plays an important role in vaccine development nanocarrier-based delivery systems that offer an opportunity to increase the cellular and humoral immune responses. The use of nanoparticles in vaccine formulations allows not only enhanced immunogenicity and stability of antigen, but also targeted delivery and slow release. Over the past decade, nanoscale size materials such as virus-like particles, liposomes, ISCOMs, polymeric, inorganic nanoparticles and emulsions have gained attention as potential delivery vehicles for vaccine antigens, which can both stabilize vaccine antigens and act as adjuvants. This advantage is attributable to the nanoscale particle size, which facilitates uptake by Antigen- Presenting Cells (APCs), then leading to efficient antigen recognition and presentation. Modifying the surfaces of nanoparticles with different targeting moieties permits the delivery of antigens to specific receptors on the cell surface, thereby stimulating selective and specific immune responses. This review provides an overview of recent advances in nanovaccinology.

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Xu, Xin, Mohamed I. Husseiny, Andreas Goldwich, and Michael Hensel. "Efficacy of Intracellular Activated Promoters for Generation of Salmonella-Based Vaccines." Infection and Immunity 78, no. 11 (August 23, 2010): 4828–38. http://dx.doi.org/10.1128/iai.00298-10.

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ABSTRACT Salmonella enterica is a versatile vaccine carrier for heterologous antigens. One strategy for vaccine antigen delivery is the use of live attenuated S. enterica strains that translocate heterologous antigens into antigen-presenting cells by means of type III secretion systems (T3SS). The feasibility of this approach has been demonstrated in various experimental vaccination studies. The efficacy of recombinant live vaccines is critically influenced by the optimal level of attenuation and many other factors. For the rational design of approaches involving translocation by T3SS, additional parameters are the level of expression of the heterologous antigens and the selection of carrier proteins for the delivery of antigens to desirable subcellular compartments of the target cell. We deployed the Salmonella pathogenicity island 2 (SPI2)-encoded T3SS for antigen delivery. The SPI2-T3SS and effector proteins are encoded by members of the large SsrAB regulon, including promoters with highly variable strength of expression. We investigated the effect of various in vivo-activated promoters of the SsrAB regulon on the efficacy of recombinant Salmonella vaccines. We observed that the use of promoters with higher strength results in greater synthesis of recombinant antigens and greater stimulation of T-cell responses in cell culture assays for the stimulation of T cells by the model antigen ovalbumin. In contrast, in vaccination experiments, promoters with a low level of expression resulted in the induction of higher amounts of T cells reactive to the model antigen listeriolysin. These results demonstrate that high-level expression of heterologous antigens does not necessarily result in optimal stimulation of immune responses.

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Zhou, Fan, and Marian R. Neutra. "Antigen Delivery to Mucosa-Associated Lymphoid Tissues Using Liposomes as a Carrier." Bioscience Reports 22, no. 2 (April 1, 2002): 355–69. http://dx.doi.org/10.1023/a:1020103109483.

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Oral vaccination requires an antigen delivery vehicle to protect the antigen and to enhance translocation of the antigen to the mucosa-associated lymphoid tissue. A variety of antigen delivery vehicles including liposomes have been studied for mucosal immunization. The advantages of liposome formulations are their particulate form and the ability to accommodate immunomodulators and targeting molecules in the same package. Many conventional liposomes are variably unstable in acids, pancreatic juice and bile. Nevertheless, carefully designed liposomes have demonstrated an impressive efficacy in inducing mucosal IgA responses, compared to free antigens and other delivery vehicles. However, liposomes as an oral vaccine vehicle are not yet optimized. To design liposomes that are stable in the harsh intestinal environment and are efficiently taken up by the M cells remains a challenge. This review summarizes recent research efforts using liposomes as an antigen carrier for oral vaccines with practical attention to liposome designs and interaction with the M cells.

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Zou, Jin-Tao, Hai-Ming Jing, Yue Yuan, Lang-Huan Lei, Zhi-Fu Chen, Qiang Gou, Qing-Shan Xiong, et al. "Pore-forming alpha-hemolysin efficiently improves the immunogenicity and protective efficacy of protein antigens." PLOS Pathogens 17, no. 7 (July 21, 2021): e1009752. http://dx.doi.org/10.1371/journal.ppat.1009752.

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Highly immunogenic exotoxins are used as carrier proteins because they efficiently improve the immunogenicity of polysaccharides. However, their efficiency with protein antigens remains unclear. In the current study, the candidate antigen PA0833 from Pseudomonas aeruginosa was fused to the α-hemolysin mutant HlaH35A from Staphylococcus aureus to form a HlaH35A-PA0833 fusion protein (HPF). Immunization with HPF resulted in increased PA0833-specific antibody titers, higher protective efficacy, and decreased bacterial burden and pro-inflammatory cytokine secretion compared with PA0833 immunization alone. Using fluorescently labeled antigens to track antigen uptake and delivery, we found that HlaH35A fusion significantly improved antigen uptake in injected muscles and antigen delivery to draining lymph nodes. Both in vivo and in vitro studies demonstrated that the increased antigen uptake after immunization with HPF was mainly due to monocyte- and macrophage-dependent macropinocytosis, which was probably the result of HPF binding to ADAM10, the Hla host receptor. Furthermore, a transcriptome analysis showed that several immune signaling pathways were activated by HPF, shedding light on the mechanism whereby HlaH35A fusion improves immunogenicity. Finally, the improvement in immunogenicity by HlaH35A fusion was also confirmed with two other antigens, GlnH from Klebsiella pneumoniae and the model antigen OVA, indicating that HlaH35A could serve as a universal carrier protein to improve the immunogenicity of protein antigens.

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Li, Shenghua, Wenju Zheng, Rhonda KuoLee, Tomoko Hirama, Matthew Henry, Shokouh Makvandi-Nejad, Ted Fjällman, Wangxue Chen, and Jianbing Zhang. "Pentabody-mediated antigen delivery induces antigen-specific mucosal immune response." Molecular Immunology 46, no. 8-9 (May 2009): 1718–26. http://dx.doi.org/10.1016/j.molimm.2009.02.007.

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Yuba, Eiji, Yoshiki Fukaya, Shin Yanagihara, Nozomi Kasho, and Atsushi Harada. "Development of Mannose-Modified Carboxylated Curdlan-Coated Liposomes for Antigen Presenting Cell Targeted Antigen Delivery." Pharmaceutics 12, no. 8 (August 11, 2020): 754. http://dx.doi.org/10.3390/pharmaceutics12080754.

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Specific delivery to antigen presenting cells (APC) and precise control of the intracellular fate of antigens are crucial to induce cellular immunity that directly and specifically attacks cancer cells. We previously achieved cytoplasmic delivery of antigen and activation of APC using carboxylated curdlan-modified liposomes, which led to the induction of cellular immunity in vivo. APCs express mannose receptors on their surface to recognize pathogen specifically and promote cross-presentation of antigen. In this study, mannose-residue was additionally introduced to carboxylated curdlan as a targeting moiety to APC for further improvement of polysaccharide-based antigen carriers. Mannose-modified curdlan derivatives were synthesized by the condensation between amino group-introduced mannose and carboxy group in pH-sensitive curdlan. Mannose residue-introduced carboxylated curdlan-modified liposomes showed higher pH-sensitivity than that of liposomes modified with conventional carboxylated curdlan. The introduction of mannose-residue to the liposomes induced aggregation in the presence of Concanavalin A, indicating that mannose residues were presented onto liposome surface. Mannose residue-introduced carboxylated curdlan-modified liposomes exhibited high and selective cellular association to APC. Furthermore, mannose residue-introduced carboxylated curdlan-modified liposomes promoted cross-presentation of antigen and induced strong antitumor effects on tumor-bearing mice. Therefore, these liposomes are promising as APC-specific antigen delivery systems for the induction of antigen-specific cellular immunity.

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Bradley, MP. "Experimental strategies for the development of an immunocontraceptive vaccine for the European red fox, Vulpes vulpes." Reproduction, Fertility and Development 6, no. 3 (1994): 307. http://dx.doi.org/10.1071/rd9940307.

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The development of an immunocontraceptive vaccine to control fox populations in Australia would confer considerable advantages in controlling the long-term impact of this predator on native and endangered species. Studies are currently under way to identify sperm antigens that might be used in such a vaccine, and some of these studies are described. It is proposed that such a vaccine would be delivered orally in a bait, thereby stimulating a mucosal immune response to the foreign antigen(s). Such a vaccine requires a detailed understanding of reproductive-tract mucosal immunity in foxes, and selection of the most effective form of antigen delivery. Those under consideration include viral or bacterial vectors and microencapsulated antigens.

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Daemen, Toos, Laura Bungener, Anke Huckriede, and Jan Wilschut. "Virosomes as an Antigen Delivery System." Journal of Liposome Research 10, no. 4 (January 2000): 329–38. http://dx.doi.org/10.3109/08982100009031103.

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Nakanishi, Tsuyoshi, Akira Hayashi, Keiichi Tanaka, and Tadanori Mayumi. "Antigen-delivery system for CTL vaccine." Drug Delivery System 14, no. 6 (1999): 459–69. http://dx.doi.org/10.2745/dds.14.459.

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Vangasseri, Dileep, Su-Ji Han, and Leaf Huang. "Lipid-Protamine-DNA-Mediated Antigen Delivery." Current Drug Delivery 2, no. 4 (October 1, 2005): 401–6. http://dx.doi.org/10.2174/156720105774370168.

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Lofthouse, S. "Immunological aspects of controlled antigen delivery." Advanced Drug Delivery Reviews 54, no. 6 (October 4, 2002): 863–70. http://dx.doi.org/10.1016/s0169-409x(02)00073-x.

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Husband, A. J., S. Bao, S. J. Mcclure, D. L. Emery, and A. J. Ramsay. "Antigen delivery strategies for mucosal vaccines." International Journal for Parasitology 26, no. 8-9 (August 1996): 825–34. http://dx.doi.org/10.1016/s0020-7519(96)80050-6.

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Journal articles on the topic 'Antigen delivery'

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