PLGA nanoparticles loaded with KMP-11 stimulate innate immunity and induce the killing of Leishmania

Santos, Diego M.; Carneiro, Marcia W.; Moura, Tatiana Rodrigues de; Soto, Manuel; Luz, Nívea F.; Prates, Deboraci B.; Irache, Juan M.; Brodskyn, Cláudia; Barral, Aldina; Barral‐Netto, Manoel; Espuelas, Socorro; Borges, Valéria M.; Oliveira, Camila I. de

doi:10.1016/j.nano.2013.04.003

Cited by 43 publications

(39 citation statements)

References 48 publications

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“…Ultimately, vaccine development is a stepwise process and using the acute model for screening vaccine candidates can be used as an effective in vivo model to determine whether a vaccine would stimulate a sufficient immune response to control parasitemia, and is frequently used in drug efficacy testing. [53][54][55] Additionally, while a concerted effort has been made to select mouse models that closely mimic human disease, the Tcell response is not directly translatable between the two species. While we predict that our findings of immunogenicity and Figure 6.…”

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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show abstract

“…In the following sections, the immunomodulatory activities of nanomaterials, including inflammasome activation, recruitment of immune cells and complement system activation, will be introduced. 12,13,21,22,33,34,[44][45][46][47][48][49][50][51][87][88][89][90] The potential mechanisms for these effects will also be discussed to facilitate an in-depth understanding of the inherent adjuvant activity of nanomaterials.…”

Section: Immunomodulatory Effects Of Nanomaterialsmentioning

confidence: 99%

“…The secretion and expression of these molecules result in the recruitment of immune cells, including macrophages, DCs, T cells, neutrophils, basophils, and eosinophils. 47,48 MF59, a nanoemulsion consisting of squalene oil, Tween 80, and sorbitan trioleate (Span 85), has been licensed in Europe for use in clinical vaccinations for influenza. This adjuvant has multifunctional activities, including enhancing antigen uptake, enhancing cytokine and chemokine release, recruiting monocytes and granulocytes to the site of injection, and augmenting the maturation of DCs and upregulation of C-C chemokine receptor 7 (CCR7).…”

Section: Complement Activationmentioning

confidence: 99%

“…Moreover, PLGA nanoparticles loaded with KMP-11 also significantly reduced the parasite load in vivo. 48 …”

Section: Complement Activationmentioning

confidence: 99%

“…In addition to their delivery function, a great number of nanoparticles have shown immunomodulatory effects, particularly for innate immune signaling. For example, nanoparticles can induce inflammasome activation in macrophages and DCs, [44][45][46] enhance antigen presentation and APC maturation, 33,34 recruit immune cells, 21,22,47,48 direct T cell differentiation to a particular subtype, and activate the complement system. 12,13,[49][50][51] Therefore, nanomaterials constitute a multifunctional unit to integrate target delivery and immunomodulation effects for clinical use in vaccination.…”

Section: Introductionmentioning

confidence: 99%

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Applications of nanomaterials as vaccine adjuvants

Zhu

Wang

Nie³

2014

Human Vaccines & Immunotherapeutics

133

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Vaccine adjuvants are applied to amplify the recipient's specific immune responses against pathogen infection or malignancy. A new generation of adjuvants is being developed to meet the demands for more potent antigenspecific responses, specific types of immune responses, and a high margin of safety. Nanotechnology provides a multifunctional stage for the integration of desired adjuvant activities performed by the building blocks of tailor-designed nanoparticles. Using nanomaterials for antigen delivery can provide high bioavailability, sustained and controlled release profiles, and targeting and imaging properties resulting from manipulation of the nanomaterials' physicochemical properties. Moreover, the inherent immune-regulating activity of particular nanomaterials can further promote and shape the cellular and humoral immune responses toward desired types. The combination of both the delivery function and immunomodulatory effect of nanomaterials as adjuvants is thought to largely benefit the immune outcomes of vaccination. In this review, we will address the current achievements of nanotechnology in the development of novel adjuvants. The potential mechanisms by which nanomaterials impact the immune responses to a vaccine and how physicochemical properties, including size, surface charge and surface modification, impact their resulting immunological outcomes will be discussed. This review aims to provide concentrated information to promote new insights for the development of novel vaccine adjuvants.

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Nanotechnology in Vaccine Development and Constraints

Foyez

Imran

2022

Nanovaccinology as Targeted Therapeutics

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PLGA nanoparticles loaded with KMP-11 stimulate innate immunity and induce the killing of Leishmania

Cited by 43 publications

References 48 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

Applications of nanomaterials as vaccine adjuvants

Nanotechnology in Vaccine Development and Constraints

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