TLR ligands and antigen need to be coencapsulated into the same biodegradable microsphere for the generation of potent cytotoxic T lymphocyte responses

Schlosser, Eva; Mueller, Marc; Fischer, Stefan; Basta, Sameh; Busch, Dirk H.; Gander, Bruno; Groettrup, Marcus

doi:10.1016/j.vaccine.2008.01.030

Cited by 239 publications

(194 citation statements)

References 54 publications

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“…Schlosser and colleagues investigated the effect of delivering antigenic protein and adjuvant (CpG oligodeoxynucleotides (ODNs), a toll-like receptor 9 (TLR9) agonist or Poly(I:C), a known TLR3 agonist) packaged in separate Poly(lactic-co-glycolic) acid (PLGA) microspheres, or coformulated within the same microsphere. As expected, co-encapsulation of antigen with a TLR agonist significantly improved antigen (cross-)presentation and induction of potent CTL responses in vivo [37]. Similar results demonstrating the need for physical association of antigen, carrier and adjuvant were obtained for liposomes by Zaks et al [38].…”

Section: Advantages Of Particulate Systems For DC Vaccination In Vivosupporting

confidence: 79%

Nanoparticle design to induce tumor immunity and challenge the suppressive tumor microenvironment

et al. 2014

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Over the years research in the field of cancer immunotherapy has flourished, bringing about crucial breakthroughs, but at the same time revealing new and important pathways of immune suppression that put a break on the success of cancer immunotherapy. This review focuses on how nano-and micromaterials can be used to induce antitumor immune responses and what their role in overcoming immune suppression could be. It is now beyond question that this requires elegantly designed particles that can reach their target cells, deliver antigenic cargo and most importantly immune stimulants in order to provoke and sustain antitumor immunity.3

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Section: Advantages Of Particulate Systems For DC Vaccination In Vivosupporting

confidence: 79%

Nanoparticle design to induce tumor immunity and challenge the suppressive tumor microenvironment

et al. 2014

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“…For polymers that degrade too slowly for antigen encapsulation schemes, such as polylactic-co-glycolic acid, adsorption of antigen onto biomaterial particles may be more beneficial 76 . Within these systems, co-encapsulation of PAMPs, such as CpG oligonucleotides or TLR4 ligands, is much more beneficial than co-administration, providing support for prolonged stimulation of dendritic cells after antigen collection [77][78][79][80] . Indeed, when dendritic cells encounter both self antigen and pathogen-derived antigen, they use the coexistence of antigen and TLR ligand within the same endosome to distinguish between the two and enhance presentation of the pathogen-derived antigen on MHC class II molecules 81 .…”

Section: Functionalization and Encapsulationmentioning

confidence: 99%

Materials engineering for immunomodulation

Hubbell

Thomas

Swartz

2009

Nature

501

423

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The engineering of materials that can modulate the immune system is an emerging field that is developing alongside immunology. For therapeutic ends such as vaccine development, materials are now being engineered to deliver antigens through specific intracellular pathways, allowing better control of the way in which antigens are presented to one of the key types of immune cell, T cells. Materials are also being designed as adjuvants, to mimic specific 'danger' signals in order to manipulate the resultant cytokine environment, which influences how antigens are interpreted by T cells. In addition to offering the potential for medical advances, immunomodulatory materials can form well-defined model systems, helping to provide new insight into basic immunobiology.The term 'immunobioengineering' is used to describe efforts by immunologists and engineers to design materials, delivery vehicles and molecules both to manipulate and to better understand the immune system. Examples are the engineering of material surfaces to induce or prevent complement activation, the engineering of adjuvants to activate the immune system, the engineering of antigen or adjuvant carriers for subunit vaccine delivery, and the engineering of microenvironments to determine the interaction kinetics of mature dendritic cells and naive T cells. These advances not only will contribute to prophylactic vaccine strategies for infectious diseases but also are likely to affect immunotherapeutics, particularly for cancer, and new approaches to prevent or treat allergies and autoimmune diseases. The field is rapidly evolving along with advances in our understanding of immunology and is also contributing to our knowledge of basic immunology.In this Review, we describe the current state of immunobioengineering as it intersects with the field of materials science, and we give a perspective on its current and future directions. We focus on materials for immunomodulation, particularly with respect to dendritic-cell modulation. We begin by providing a brief introduction to the targets for delivery: the types of cell that materials are being designed to target, the tissues in which those cells reside, the intracellular compartments within those cells, and the influence that delivery to those particular compartments has on immunological outcome. We then discuss the biomolecular payloads used to activate immune cells and the design of the materials used to deliver those 'danger' signals along with, in the context of vaccination, antigens. Finally, we highlight materials approaches that are being developed to explore basic immunological function, especially how dendritic cells and T cells interact. Tissue and cellular targetsAs the general goals of immunobioengineering are to probe and manipulate the immune system, we start with a general discussion of tissue, cellular and subcellular targets -what we want to target and why -to guide the design principles discussed below.The immune cells most frequently targeted include B cells, macrophages and dendritic cells, wh...

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“…Previous studies have shown that model antigen-and adjuvant-loaded PLGA nanoparticles used for vaccination were able to improve the induction of cell-mediated immune response in mice [17,[21][22][23]. However, relatively little is known about how encapsulation in PLGA nanoparticles modifies T cell responses to antigen/adjuvant combinations that are delivered intradermally by different novel types of microneedles.…”

Section: Introductionmentioning

confidence: 99%

Hollow microneedle-mediated intradermal delivery of model vaccine antigen-loaded PLGA nanoparticles elicits protective T cell-mediated immunity to an intracellular bacterium

Groot

Mönkäre

et al. 2017

Journal of Controlled Release

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A B S T R A C TThe skin is an attractive organ for immunization due to the presence of a large number of epidermal and dermal antigen-presenting cells. Hollow microneedles allow for precise and non-invasive intradermal delivery of vaccines. In this study, ovalbumin (OVA)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles with and without TLR3 agonist poly(I:C) were prepared and administered intradermally by hollow microneedles. The capacity of the PLGA nanoparticles to induce a cytotoxic T cell response, contributing to protection against intracellular pathogens, was examined. We show that a single injection of OVA-loaded PLGA nanoparticles, compared to soluble OVA, primed both adoptively transferred antigen-specific naïve transgenic CD8 + and CD4 + T cells with markedly high efficiency. Applying a triple immunization protocol, PLGA nanoparticles primed also endogenous OVA-specific CD8 + T cells. Immune response, following immunization with in particular anionic PLGA nanoparticles co-encapsulated with OVA and poly(I:C), provided protection against a recombinant strain of the intracellular bacterium Listeria monocytogenes, secreting OVA. Taken together, we show that PLGA nanoparticle formulation is an excellent delivery system for protein antigen into the skin and that protective cellular immune responses can be induced using hollow microneedles for intradermal immunizations.

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TLR ligands and antigen need to be coencapsulated into the same biodegradable microsphere for the generation of potent cytotoxic T lymphocyte responses

Cited by 239 publications

References 54 publications

Nanoparticle design to induce tumor immunity and challenge the suppressive tumor microenvironment

Nanoparticle design to induce tumor immunity and challenge the suppressive tumor microenvironment

Materials engineering for immunomodulation

Hollow microneedle-mediated intradermal delivery of model vaccine antigen-loaded PLGA nanoparticles elicits protective T cell-mediated immunity to an intracellular bacterium

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