HIV-Antigens Charged on Phosphorus Dendrimers as Tools for Tolerogenic Dendritic Cells-Based Immunotherapy

Vacas-Córdoba, Enrique; Bastida, Hugo; Pion, Marjorie; Hameau, Aurélien; Йонов, Максим; Bryszewska, Maria; Caminade, Anne‐Marie; Majoral, Jean Pierre; Muñoz‐Fernández, María Ángeles

doi:10.2174/0929867321666131129114022

Cited by 21 publications

(18 citation statements)

References 47 publications

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“…8,9,14,15 Eight dendrimers were dissolved in distilled water in a final concentration of 1 mM. Dilutions to µM range were generated in distilled water from the stock.…”

Section: Materials and Methods Compoundsmentioning

confidence: 99%

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Prevention of vaginal and rectal herpes simplex virus type 2 transmission in mice: mechanism of antiviral action

Ceña-Díez¹,

Vacas-Córdoba²,

García-Broncano³

et al. 2016

IJN

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Topical microbicides to stop sexually transmitted diseases, such as herpes simplex virus type 2 (HSV-2), are urgently needed. The emerging field of nanotechnology offers novel suitable tools for addressing this challenge. Our objective was to study, in vitro and in vivo, antiherpetic effect and antiviral mechanisms of several polyanionic carbosilane dendrimers with anti-HIV-1 activity to establish new potential microbicide candidates against sexually transmitted diseases. Plaque reduction assay on Vero cells proved that G2-S16, G1-S4, and G3-S16 are the dendrimers with the highest inhibitory response against HSV-2 infection. We also demonstrated that our dendrimers inhibit viral infection at the first steps of HSV-2 lifecycle: binding/entry-mediated events. G1-S4 and G3-S16 bind directly on the HSV-2, inactivating it, whereas G2-S16 adheres to host cell-surface proteins. Molecular modeling showed that G1-S4 binds better at binding sites on gB surface than G2-S16. Significantly better binding properties of G1-S4 than G2-S16 were found in an important position for affecting transition of gB trimer from G1-S4 prefusion to final postfusion state and in several positions where G1-S4 could interfere with gB/gH–gL interaction. We demonstrated that these polyanionic carbosilan dendrimers have a synergistic activity with acyclovir and tenofovir against HSV-2, in vitro. Topical vaginal or rectal administration of G1-S4 or G2-S16 prevents HSV-2 transmission in BALB/c mice in values close to 100%. This research represents the first demonstration that transmission of HSV-2 can be blocked by vaginal/rectal application of G1-S4 or G2-S16, providing a step forward to prevent HSV-2 transmission in humans.

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“…8,9,14,15 Eight dendrimers were dissolved in distilled water in a final concentration of 1 mM. Dilutions to µM range were generated in distilled water from the stock.…”

Section: Materials and Methods Compoundsmentioning

confidence: 99%

“…8,14,15,17 The effect of polyanionic dendrimers in HSV-2 binding was studied ( Figure 3B). The attachment of HSV-2 to Vero cells was inhibited in a doseresponse effect by the three dendrimers ( Figure 3B).…”

mentioning

confidence: 99%

Prevention of vaginal and rectal herpes simplex virus type 2 transmission in mice: mechanism of antiviral action

Ceña-Díez¹,

Vacas-Córdoba²,

García-Broncano³

et al. 2016

IJN

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“…This has led to the exploration of novel ways of antigen administering including adenovirus 5-mediated delivery of DNA without positive results [ 12 ]. Another approach for developing HIV vaccines has led to the use of nanoparticles as delivery agents for HIV antigenic peptides to antigen presenting cells (APCs) to elicit a therapeutic response [ 13 ]. We explored this approach using a cationic phosphorous dendrimer which failed to induce an efficient antigenic response [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle-Delivered HIV Peptides to Dendritic Cells a Promising Approach to Generate a Therapeutic Vaccine

et al. 2020

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Finding a functional cure for HIV-1 infection will markedly decrease the social and economic burden of this disease. In this work, we have taken advantage of the antigen presenting cell role of human dendritic cells (DCs) to try to induce an immune response to HIV-derived peptide delivered to DCs using two different polycationic nanoparticles: a G4 PAMAM dendrimer modified to a 70/30 ratio of hydroxyl groups/amines and a cyclodextrin derivative. We have studied peptide delivery using a fluorescence peptide and have studied the immune response generation by cytokine determination and flow cytometry. We have found a robust delivery of the antigenic peptide to DCs and activated dendritic cell-mediated peripheral blood mononuclear cells (PBMCs) proliferation using the mixed lymphocyte reaction. However, no expression of markers indicating activation of either B or T lymphocytes was observed. Moreover, the release of the pro-inflammatory cytokine TNF-α or IL-2 was only observed when DCs treated with either the dendrimer or the dendriplex containing the peptide. Antigenic peptide delivery to DCs is a promising approach to generate a vaccine against HIV-1 infection. However, more studies, including the simultaneous delivery of several antigenic peptides from different viral proteins, can markedly improve the immune response.

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“…The focus must now be on the development of new preventive and therapeutic vaccines, and their effective delivery into the target cells. The application of dendritic cells (DCs) as a vaccine adjuvant is one way to improve deterioration of immune functioning in HIV-1-infected individuals [4,5]. For therapeutic purposes, the antigen (HIV-derived peptide) should be transported through the cell membrane into the cytoplasm.…”

Section: Introductionmentioning

confidence: 99%

“…Dendrimers are hyperbranched, multifunctional and completely defined macromolecules that are already known to have high therapeutic potential in delivering biomolecules [5,6,15]. Among various types of cationic dendrimers of different generation, the carbosilane dendrimers (CBD) of second generation are of special interest.…”

Section: Introductionmentioning

confidence: 99%

Dendrimers complexed with HIV-1 peptides interact with liposomes and lipid monolayers

Йонов

Ciepluch

Garaiova

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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HIV-Antigens Charged on Phosphorus Dendrimers as Tools for Tolerogenic Dendritic Cells-Based Immunotherapy

Cited by 21 publications

References 47 publications

Prevention of vaginal and rectal herpes simplex virus type 2 transmission in mice: mechanism of antiviral action

Prevention of vaginal and rectal herpes simplex virus type 2 transmission in mice: mechanism of antiviral action

Nanoparticle-Delivered HIV Peptides to Dendritic Cells a Promising Approach to Generate a Therapeutic Vaccine

Dendrimers complexed with HIV-1 peptides interact with liposomes and lipid monolayers

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