Time course study of the antigen-specific immune response to a PLGA microparticle vaccine formulation

Wang, Qian; Tan, Melody T.; Keegan, Brian; Barry, Meagan A.; Heffernan, Michael J.

doi:10.1016/j.biomaterials.2014.05.067

Cited by 57 publications

(46 citation statements)

References 52 publications

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“…This T H 1-biasing is primarily due to the pathway activated in binding of CpG ODN by TLR-9 in the endolysosome of antigen-presenting cells, 46 but is likely also enhanced by the PLGA nanoparticle delivery system, which enhances antigen uptake by antigen-presenting cells, 32 facilitates uptake of CpG ODN into the endolysosome, 47 and increases MHC I antigen presentation. 36 Overall, the vaccine containing both the CpG ODN immunomodulatory adjuvant and the PLGA nanoparticle delivery system was necessary to produce a robust Figure 4. Tc24-specific antibody response.…”

Section: Discussionmentioning

confidence: 99%

“…23,[28][29][30] Nanoparticles have been shown to increase antigen uptake by antigen-presenting cells 31 and enhance the T H 1-mediated CD8 C T cell response [32][33][34] through increased MHC I antigen presentation. 35 Nanoparticles can also serve as a depot for antigen, 36 allowing prolonged stimulation of the T H 1 pathway. 37 A common polymer used in nanoparticle synthesis is poly(lactic-co-glycolic acid) (PLGA).…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Introductionmentioning

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 results of this study gives applicable data for designing optimal vaccination regimens in MP-based protein vaccines. 102 However, it was found that polymer nature and MP characteristics are 2 affecting factors in the outcome of CpG and antigen co-encapsulating. For example, when OVA and CpG sequences were coencapsulated into Resomer Ò RG PLGA 502 and 756 MPs, no improvement in cellular immune response was seen in Table 6.…”

Section: Cpgmentioning

confidence: 99%

“…102,103 For example, 3 formulations including addition of CpG in soluble form, CpG adsorption on, and CpG encapsulation into PLGA MPs with the adsorbed protein antigen from Neisseriameningitidis B were evaluated. The results indicated that CpG encapsulated formulations led to increased immunopotentiator effect which was indicated by significant higher antibody, bactericidal activity and T cell responses when compared to the traditional method of delivering CpG in the soluble form.…”

Section: Cpgmentioning

confidence: 99%

Peptide/protein vaccine delivery system based on PLGA particles

Allahyari

Mohit

2015

Human Vaccines & Immunotherapeutics

172

107

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Due to the excellent safety profile of poly (D,L-lactide-co-glycolide) (PLGA) particles in human, and their biodegradability, many studies have focused on the application of PLGA particles as a controlled-release vaccine delivery system. Antigenic proteins/peptides can be encapsulated into or adsorbed to the surface of PLGA particles. The gradual release of loaded antigens from PLGA particles is necessary for the induction of efficient immunity. Various factors can influence protein release rates from PLGA particles, which can be defined intrinsic features of the polymer, particle characteristics as well as protein and environmental related factors. The use of PLGA particles encapsulating antigens of different diseases such as hepatitis B, tuberculosis, chlamydia, malaria, leishmania, toxoplasma and allergy antigens will be described herein. The co-delivery of antigens and immunostimulants (IS) with PLGA particles can prevent the systemic adverse effects of immunopotentiators and activate both dendritic cells (DCs) and natural killer (NKs) cells, consequently enhancing the therapeutic efficacy of antigen-loaded PLGA particles. We will review co-delivery of different TLR ligands with antigens in various models, highlighting the specific strengths and weaknesses of the system. Strategies to enhance the immunotherapeutic effect of DCbased vaccine using PLGA particles can be designed to target DCs by functionalized PLGA particle encapsulating siRNAs of suppressive gene, and disease specific antigens. Finally, specific examples of cellular targeting where decorating the surface of PLGA particles target orally administrated vaccine to Mcells will be highlighted.

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“…One approach for studying in vivo release kinetics is to use non-invasive imaging with fluorescently-labeled antigens to assess vaccine depletion from controlled release depots over time. This technique has been used for one study, but has yet to be validated [191].…”

Section: Antigen Release Kineticsmentioning

confidence: 99%