Induction of a balanced Th1/Th2 immune responses by co-delivery of PLGA/ovalbumin nanospheres and CpG ODNs/PEI-SWCNT nanoparticles as TLR9 agonist in BALB/c mice

Ebrahimian, Mahboubeh; Hashemi, Maryam; Maleki, Mohsen; Abnous, Khalil; Hashemitabar, Gholamreza; Ramezani, Mohammad; Haghparast, Alireza

doi:10.1016/j.ijpharm.2016.10.065

Cited by 26 publications

(13 citation statements)

References 56 publications

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“…Recently, we have described a novel delivery vehicle for TLR9 ligand (CpG ODN) based on single-walled carbon nanotube functionalized with PEI and demonstrated its efficacy in induction of Th1/Th2 immune responses in mice ( 27 ). Given the pivotal role of PRRs and specially TLRs in initiating and tuning of immune responses in the context of vaccine-adjuvant development, the present study was conducted to synthesize and evaluate a PLGA NP-based adjuvant delivery platform using multiple TLRs (TLR4, TLR7/8, and TLR9) agonists.…”

Section: Discussionmentioning

confidence: 99%

“…Potential weakness of PEI is that high molecular PEI is toxic to cells due to plasma membrane and/or lysosomal damage by the proton-sponge effects ( 32 , 33 ). Thus, PEI with optimal molecular weight (10 kDa) which we used in this study is considered to be safe and effective in the context of adjuvant development and can deliver the adjuvant cargo to the phagosome compartment of APCs efficiently ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

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Co-delivery of Dual Toll-Like Receptor Agonists and Antigen in Poly(Lactic-Co-Glycolic) Acid/Polyethylenimine Cationic Hybrid Nanoparticles Promote Efficient In Vivo Immune Responses

et al. 2017

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Strategies to design delivery vehicles are critical in modern vaccine-adjuvant development. Nanoparticles (NPs) encapsulating antigen(s) and adjuvant(s) are promising vehicles to deliver antigen(s) and adjuvant(s) to antigen-presenting cells (APCs), allowing optimal immune responses against a specific pathogen. In this study, we developed a novel adjuvant delivery approach for induction of efficient in vivo immune responses. Polyethylenimine (PEI) was physically conjugated to poly(lactic-co-glycolic) acid (PLGA) to form PLGA/PEI NPs. This complex was encapsulated with resiquimod (R848) as toll-like receptor (TLR) 7/8 agonist, or monophosphoryl lipid A (MPLA) as TLR4 agonist and co-assembled with cytosine–phosphorothioate–guanine oligodeoxynucleotide (CpG ODN) as TLR9 agonist to form a tripartite formulation [two TLR agonists (inside and outside NPs) and PLGA/PEI NPs as delivery system]. The physicochemical characteristics, cytotoxicity and cellular uptake of these synthesized delivery vehicles were investigated. Cellular viability test revealed no pronounced cytotoxicity as well as increased cellular uptake compared to control groups in murine macrophage cells (J774 cell line). In the next step, PLGA (MPLA or R848)/PEI (CpG ODN) were co-delivered with ovalbumin (OVA) encapsulated into PLGA NPs to enhance the induction of immune responses. The immunogenicity properties of these co-delivery formulations were examined in vivo by evaluating the cytokine (IFN-γ, IL-4, and IL-1β) secretion and antibody (IgG1, IgG2a) production. Robust and efficient immune responses were achieved after in vivo administration of PLGA (MPLA or R848)/PEI (CpG ODN) co-delivered with OVA encapsulated in PLGA NPs in BALB/c mice. Our results demonstrate a rational design of using dual TLR agonists in a context-dependent manner for efficient nanoparticulate adjuvant-vaccine development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Co-delivery of Dual Toll-Like Receptor Agonists and Antigen in Poly(Lactic-Co-Glycolic) Acid/Polyethylenimine Cationic Hybrid Nanoparticles Promote Efficient In Vivo Immune Responses

et al. 2017

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“…Generally, IgG2a and IgG2b antibodies are related with Th1-type immune response and IgG1 antibodies are mediated Th2-type immune response. 36 As shown in Figure 7C, on days 28, 35, and42 after primary immunization, CYPP-PEI/PCV-2 group produced significantly higher levels of IgG1 (Th2-associated isotype) compared with other control groups except for ISA-206/PCV-2 group (P<0.05). In addition, the highest levels of IgG2a and IgG2b (Th2-associated isotype) were showed in CYPP-PEI /PCV-2 group on days 28, 35, and 42 after primary immunization ( Figure 7D and E).…”

Section: Serum Antibody Response After Vaccination In Micementioning

confidence: 82%

<p>The Immunoenhancement Effects of Polyethylenimine-Modified Chinese Yam Polysaccharide-Encapsulated PLGA Nanoparticles as an Adjuvant</p>

Zhang¹,

Gu²,

Wusiman³

et al. 2020

IJN

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Background: Poly(lactic-co-glycolic acid) (PLGA) has been extensively applied for sustained drug delivery and vaccine delivery system. However, vaccines delivered by PLGA nanoparticles alone could not effectively activate antigen-presenting cells (APCs) to induce strong immune responses. Purpose: The aim of the present study was to design polyethylenimine (PEI)-modified Chinese yam polysaccharide (CYP)-encapsulated PLGA nanoparticles (CYPP-PEI) as a vaccine delivery system and evaluate the adjuvant activities in vitro and in vivo. Materials and Methods: Cationic-modified nanoparticles exhibited high antigen absorption and could be efficiently taken by APCs to enhance the immune responses. Therefore, PEI-modified CYP-encapsulated PLGA nanoparticles (CYPP-PEI) were prepared. The storage stability and effective adsorption capacity for porcine circovirus-2 (PCV-2) antigen of these antigen-absorbed nanoparticles were measured for one month. Furthermore, the adjuvant activity of CYPP-PEI nanoparticles was evaluated on macrophages in vitro and through immune responses triggered by PCV-2 antigen in vivo. Results: The PCV-2 absorbed CYPP-PEI nanoparticles showed excellent storage stability and high absorption efficiency of PCV-2 antigen. In vitro, CYPP-PEI nanoparticles promoted antigen uptake, enhanced surface molecular expressions of CD80 and CD86, and improved cytokine secretion of TNF-α, IFN-γ, and IL-12p70 in macrophages. After immunization with CYPP-PEI/PCV-2 formulation in mice, the expressions of surface activation markers on dendritic cells which located in draining lymph nodes were increased, such as MHCI, MHCII, and CD80. In addition, CYPP-PEI nanoparticles induced dramatically high PCV-2-specific IgG levels which could last for a long time and stimulated the secretion of subtype antibodies and cytokines. The results showed that CYPP-PEI could induce Th1/Th2 mixed but Th1-biased type immune responses. Conclusion: Polyethylenimine-modified Chinese yam polysaccharide-encapsulated PLGA nanoparticle was a potential vaccine delivery system to trigger strong and persistent immune responses.

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“…The expression of CD86, CD80 and CD40 in B cells and PDCs after TLR9 activation increased Th1 Type immune response and chemokine secretion also increased, such as monocyte inflammatory protein-1, IL-6, IL-12, IP-10 and so on. The overall effect of TLR9 activation is to induce innate immunity and acquired immune systems to produce cellular and humoral immune responses that are biased towards Th1 type [32][33][34] .…”

Section: Regulation Of Cpg-dna On Immune Signaling Pathwaysmentioning

confidence: 99%

Research progress of CpG-DNA in regulation of immune system and signal pathway

Wang

Yang

2017

J. Appl. Virol.

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CpG-DNA is a DNA sequence with immunostimulatory function as the core of unmethylated CpG motif. It includes synthetic oligodeoxynucleotides containing CpG motifs and genomic DNA of lower organisms such as bacteria, viruses, and invertebrates. CpG-DNA as a potential immunostimulatory factor can be recognized by the vertebrate natural immune system, rapid activation of natural immune response. It can trigger a protective immune response to remove foreign pathogens. CpG-DNA activated cell signaling mechanisms include endocytosis of CpG-DNA, specificity with Toll-like receptor 9 and a series of signal cascades that induce the expression of target genes and Feedback by various endogenous factors. This paper reviews the basic concepts of CpG-DNA, the characteristics of TLR9 receptors, the regulation of the immune system and its signaling pathways.

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Induction of a balanced Th1/Th2 immune responses by co-delivery of PLGA/ovalbumin nanospheres and CpG ODNs/PEI-SWCNT nanoparticles as TLR9 agonist in BALB/c mice

Cited by 26 publications

References 56 publications

Co-delivery of Dual Toll-Like Receptor Agonists and Antigen in Poly(Lactic-Co-Glycolic) Acid/Polyethylenimine Cationic Hybrid Nanoparticles Promote Efficient In Vivo Immune Responses

Co-delivery of Dual Toll-Like Receptor Agonists and Antigen in Poly(Lactic-Co-Glycolic) Acid/Polyethylenimine Cationic Hybrid Nanoparticles Promote Efficient In Vivo Immune Responses

<p>The Immunoenhancement Effects of Polyethylenimine-Modified Chinese Yam Polysaccharide-Encapsulated PLGA Nanoparticles as an Adjuvant</p>

Research progress of CpG-DNA in regulation of immune system and signal pathway

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