Protective efficiency of dendrosomes as novel nano-sized adjuvants for DNA vaccination against birch pollen allergy

Balenga, Nariman; Zahedifard, Farnaz; Weiss, Richard; Sarbolouki, M. N.; Thalhamer, Joseph; Rafati, Sima

doi:10.1016/j.jbiotec.2006.01.014

Cited by 41 publications

(21 citation statements)

References 37 publications

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“…The immune responses peaked by 6-8 weeks and displayed a Th1 bias. Another study by Balenga et al 26 reported successful genetic vaccination against birch pollen allergy, mediated by Den123, a nontoxic selfassembled dendritic spheroidal nanoparticle made of biodegradable monomers. The authors reported a Th1/Th2 balanced …”

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confidence: 99%

Enhancement of immunogenicity and efficacy of a plasmid DNA rabies vaccine by nanoformulation with a fourth-generation amine-terminated poly(ether imine) dendrimer

Ullas¹,

Madhusudana²,

Desai³

et al. 2014

IJN

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Purpose Delayed onset of, and low magnitude of, protective immune responses are major drawbacks limiting the practical utility of plasmid vaccination against rabies. In this study we evaluated whether nanoformulation with the novel poly(ether imine) (PETIM) dendrimer can enhance the immunogenicity and efficacy of a plasmid-based rabies vaccine. Materials and methods A plasmid vaccine construct (pIRES-Rgp) was prepared by cloning the full-length rabies virus glycoprotein gene into pIRES vector. Drawing upon the results of our previous study, a dendriplex (dendrimer-DNA complex) of pIRES-Rgp was made with PETIM dendrimer (10:1 w/w, PETIM:pIRES-Rgp). In vitro transfection was done on baby hamster kidney (BHK)-21 cells to evaluate expression of glycoprotein gene from pIRES-Rgp and PETIM-pIRES-Rgp. Subsequently, groups of Swiss albino mice were immunized intramuscularly with pIRES-Rgp or PETIM-pIRES-Rgp. A commercially available cell culture rabies vaccine was included for comparison. Rabies virus neutralizing antibody (RVNA) titers in the immune sera were evaluated on days 14, 28, and 90 by rapid fluorescent focus inhibition test. Finally, an intracerebral challenge study using a challenge virus standard strain of rabies virus was done to evaluate the protective efficacy of the formulations. Results Protective levels of RVNA titer (≥0.5 IU/mL) were observed by day 14 in animals immunized with pIRES-Rgp and its dendriplex. Notably, PETIM-pIRES-Rgp produced 4.5-fold higher RVNA titers compared to pIRES-Rgp at this time point. All mice immunized with the PETIM-pIRES-Rgp survived the intracerebral rabies virus challenge, compared with 60% in the group which received pIRES-Rgp. Conclusion Our results suggest that nanoformulation with PETIM dendrimer can produce an earlier onset of a high-titered protective antibody response to a plasmid-based rabies vaccine. PETIM dendriplexing appears to be an efficacious nonviral delivery strategy to enhance genetic vaccination.

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confidence: 99%

Enhancement of immunogenicity and efficacy of a plasmid DNA rabies vaccine by nanoformulation with a fourth-generation amine-terminated poly(ether imine) dendrimer

Ullas¹,

Madhusudana²,

Desai³

et al. 2014

IJN

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“…These findings suggest that PVA-SPIONs possess an intrinsic capacity for immune-modulation and may potentially provide a form of tolerance induction by affecting DC function. There are several lines of evidence in the literature demonstrating that other types of nanoparticles may induce a degree of desirable immune-suppression: synthetic peptide dendrimers inhibited experimental allergic encephalomyelitis, allergen-loaded nanoparticles and dendrimers downregulated allergic reactions to environmental and food allergens, and a fullerene derivative polyhydroxy C60 prevented type I hypersensitivity reactions (Scholl et al 2004;Balenga et al 2006;Gomez et al 2007Gomez et al , 2008Wegmann et al 2008). Size, surface charge and coating may confer to a nanoparticle its intrinsic properties that may lead to immune-suppression.…”

Section: Discussionmentioning

confidence: 99%

Biomedical nanoparticles modulate specific CD4⁺T cell stimulation by inhibition of antigen processing in dendritic cells

et al. 2011

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Understanding how nanoparticles may affect immune responses is an essential prerequisite to developing novel clinical applications. To investigate nanoparticle-dependent outcomes on immune responses, dendritic cells (DCs) were treated with model biomedical poly(vinylalcohol)-coated super-paramagnetic iron oxide nanoparticles (PVA-SPIONs). PVA-SPIONs uptake by human monocyte-derived DCs (MDDCs) was analyzed by flow cytometry (FACS) and advanced imaging techniques. Viability, activation, function, and stimulatory capacity of MDDCs were assessed by FACS and an in vitro CD4 + T cell assay. PVA-SPION uptake was dose-dependent, decreased by lipopolysaccharide (LPS)-induced MDDC maturation at higher particle concentrations, and was inhibited by cytochalasin D pre-treatment. PVA-SPIONs did not alter surface marker expression (CD80, CD83, CD86, myeloid/plasmacytoid DC markers) or antigen-uptake, but decreased the capacity of MDDCs to process antigen, stimulate CD4 + T cells, and induce cytokines. The decreased antigen processing and CD4 + T cell stimulation capability of MDDCs following PVA-SPION treatment suggests that MDDCs may revert to a more functionally immature state following particle exposure.

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“…In vitro superior transfection efficiency displayed by PAMAM dendrosomes as comparison to other nonviral gene delivery vectors. Nontoxic self-assembled dendritic spheroidal nanoparticles (Den123) have been used for the delivery of pCMV-Betv1 loaded dendritic spheroidal nanoparticles (Den123) have shown low toxicity, enhanced transfection efficiency, and improved the immune response against birch pollen allergy (Balenga et al 2006). Similarly, efficiency of dendrosome (a gene porter) is assessed in transferring recombinant human rotavirus VP2 cDNA.…”

Section: Dendrosomesmentioning

confidence: 99%

Nanotechnological Approaches for Genetic Immunization

2013

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Genetic immunization is one of the important findings that provide multifaceted immunological response against infectious diseases. With the advent of r-DNA technology, it is possible to construct vector with immunologically active genes against specific pathogens. Nevertheless, site-specific delivery of constructed genetic material is an important contributory factor for eliciting specific cellular and humoral immune response. Nanotechnology has demonstrated immense potential for the site-specific delivery of biomolecules. Several polymeric and lipidic nanocarriers have been utilized for the delivery of genetic materials. These systems seem to have better compatibility, low toxicity, economical and capable to delivering biomolecules to intracellular site for the better expression of desired antigens. Further, surface engineering of nanocarriers and targeting approaches have an ability to offer better presentation of antigenic material to immunological cells. This chapter gives an overview of existing and emerging nanotechnological approaches for the delivery of genetic materials.

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Protective efficiency of dendrosomes as novel nano-sized adjuvants for DNA vaccination against birch pollen allergy

Cited by 41 publications

References 37 publications

Enhancement of immunogenicity and efficacy of a plasmid DNA rabies vaccine by nanoformulation with a fourth-generation amine-terminated poly(ether imine) dendrimer

Enhancement of immunogenicity and efficacy of a plasmid DNA rabies vaccine by nanoformulation with a fourth-generation amine-terminated poly(ether imine) dendrimer

Biomedical nanoparticles modulate specific CD4⁺T cell stimulation by inhibition of antigen processing in dendritic cells

Nanotechnological Approaches for Genetic Immunization

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Protective efficiency of dendrosomes as novel nano-sized adjuvants for DNA vaccination against birch pollen allergy

Cited by 41 publications

References 37 publications

Enhancement of immunogenicity and efficacy of a plasmid DNA rabies vaccine by nanoformulation with a fourth-generation amine-terminated poly(ether imine) dendrimer

Enhancement of immunogenicity and efficacy of a plasmid DNA rabies vaccine by nanoformulation with a fourth-generation amine-terminated poly(ether imine) dendrimer

Biomedical nanoparticles modulate specific CD4+T cell stimulation by inhibition of antigen processing in dendritic cells

Nanotechnological Approaches for Genetic Immunization

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Biomedical nanoparticles modulate specific CD4⁺T cell stimulation by inhibition of antigen processing in dendritic cells