The potency of the adjuvant, CpG oligos, is enhanced by encapsulation in PLG microparticles

Malyala, Padma; Chesko, James; Ugozzoli, Mildred; Goodsell, Amanda; Zhou, Fengmin; Vajdy, Michael; O’Hagan, Derek T.; Singh, Manmohan

doi:10.1002/jps.21065

Cited by 48 publications

(33 citation statements)

References 16 publications

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“…37 They are also consistent with reported studies showing T H 1-biased enhancement of other protein antigens when combined with CpG ODN in PLGA nanoparticles. [48][49][50] Other therapeutic vaccines against Chagas disease have been found to induce a protective antigen-specific CD8 C T cell population that expands upon challenge with infection and produces T H 1-associated cytokines that include IFNg and TNFa, 51 as well as a CD4 C T cell population capable of IFNg production. 24 Our results are consistent with these findings, though further characterization of the immune response could be pursued to determine the cell types responsible for protection in this model.…”

Section: Discussionmentioning

confidence: 99%

A therapeutic nanoparticle vaccine againstTrypanosoma cruziin a BALB/c mouse model of Chagas disease

Barry

Wang

Jones

et al. 2016

Human Vaccines & Immunotherapeutics

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Chagas disease, caused by Trypanosoma cruzi, results in an acute febrile illness that progresses to chronic chagasic cardiomyopathy in 30% of patients. Current treatments have significant side effects and poor efficacy during the chronic phase; therefore, there is an urgent need for new treatment modalities. A robust T H 1-mediated immune response correlates with favorable clinical outcomes. A therapeutic vaccine administered to infected individuals could bolster the immune response, thereby slowing or stopping the progression of chagasic cardiomyopathy. Prior work in mice has identified an efficacious T. cruzi DNA vaccine encoding Tc24. To elicit a similar protective cell-mediated immune response to a Tc24 recombinant protein, we utilized a poly(lactic-co-glycolic acid) nanoparticle delivery system in conjunction with CpG motif-containing oligodeoxynucleotides as an immunomodulatory adjuvant. In a BALB/c mouse model, the vaccine produced a T H 1-biased immune response, as demonstrated by a significant increase in antigen-specific IFNg-producing splenocytes, IgG2a titers, and proliferative capacity of CD8 C T cells. When tested for therapeutic efficacy, significantly reduced systemic parasitemia was seen during peak parasitemia. Additionally, there was a significant reduction in cardiac parasite burden and inflammatory cell infiltrate. This is the first study demonstrating immunogenicity and efficacy of a therapeutic Chagas vaccine using a nanoparticle delivery system.

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Section: Discussionmentioning

confidence: 99%

A therapeutic nanoparticle vaccine againstTrypanosoma cruziin a BALB/c mouse model of Chagas disease

Barry

Wang

Jones

et al. 2016

Human Vaccines & Immunotherapeutics

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“…The immunogenicity enhancement can be comparable to that by traditional aluminum hydroxide-adjuvanted vaccine [225]; or even better than that by more advanced adjuvant such as Montanide ISA 720 [226]. Using poly (lactide-co-glycolide) as a model polymer and Neisseria meningitidis serotype B (Men B) as a model antigen, encapsulating CpG within PLG microparticles induced statistically significant higher antibody, bactericidal activity and T cell responses when compared to the soluble form of CpG [206].…”

Section: Polymeric Solutions or Particulatesmentioning

confidence: 99%

“…Various polymers have been demonstrated to have such properties, such as polylactic acid (PLA), poly (lactide-co-glycolide) acid (PLGA) [206,207], chitosan [208][209][210][211] or modified chitosan [207], poly(-glutamic acid) (-PGA) [212,213], polypeptides [204], starch [214,215], polystyrene [35,205], polyphosphazene [216], poly (prolylene sulfide) [217], polyethylene glycol [218], alginate [219], and their copolymers [220,221]. They enhance immunogenicity through several mechanisms, including enhancement of antigen uptake by dendritic cells (in vitro) [212], maturation of dendritic cells [212], promotion of proliferation of antigen-specific T cells [212], stimulation of both B and T lymphocytes [208], facilitation of activation of dendritic cells [222], viscosity-induced retention of antigens in the vaccination site [210] and controlled release of antigen by particles [223,224].…”

Section: Polymeric Solutions or Particulatesmentioning

confidence: 99%

“…Antigens can either be adsorbed on the surface or encapsulated inside the polymeric particles. Intramuscular administration of adsorbed antigen -Neisseria meningitidis serotype B (Men B) (99% adsorption efficiency) on PLGA particulates with CpG significantly increased the anti-Men B serum antibody titers and serum bactericidal titer in mice [206]. The immunogenicity enhancement can be comparable to that by traditional aluminum hydroxide-adjuvanted vaccine [225]; or even better than that by more advanced adjuvant such as Montanide ISA 720 [226].…”

Section: Polymeric Solutions or Particulatesmentioning

confidence: 99%

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Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

Self Cite

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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

513

428

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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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The potency of the adjuvant, CpG oligos, is enhanced by encapsulation in PLG microparticles

Cited by 48 publications

References 16 publications

A therapeutic nanoparticle vaccine againstTrypanosoma cruziin a BALB/c mouse model of Chagas disease

A therapeutic nanoparticle vaccine againstTrypanosoma cruziin a BALB/c mouse model of Chagas disease

Selection of Adjuvants for Enhanced Vaccine Potency

Materials engineering for immunomodulation

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