The effect of stable macromolecular complexes of ionic polyphosphazene on HIV Gag antigen and on activation of human dendritic cells and presentation to T-cells

Palmer, Christine D.; Ninković, Jana; Prokopowicz, Zofia; Mancuso, Christy J.; Marin, Alexander; Andrianov, Alexander K.; Dowling, David J.; Levy, Ofer

doi:10.1016/j.biomaterials.2014.06.043

Cited by 33 publications

(34 citation statements)

References 47 publications

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“…0.35 ml clinical-grade saline (sterile/ pyrogen-free 0.9% NaCl solution for injection) was used as a placebo control. Oil droplet particle size was determined by dynamic light scattering using a Zetasizer nanoseries instrument (Malvern Nano-ZS, l 1⁄4 532 nm) as previously described (49). The particle size data refer to scattering intensity distributions (z-average) with accompanying polydispersity/heterogeneity index (PDI), with a PDI < 0.2 considered monodisperse.…”

Section: Methodsmentioning

confidence: 99%

TLR7/8 adjuvant overcomes newborn hyporesponsiveness to pneumococcal conjugate vaccine at birth

et al. 2017

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Section: Methodsmentioning

confidence: 99%

TLR7/8 adjuvant overcomes newborn hyporesponsiveness to pneumococcal conjugate vaccine at birth

et al. 2017

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“…To further characterize the innate immune effects of OMV formulations, 96-well human MoDC-based arrays were generated after culturing CD14 selected monocytes with IL-4 and GM-CSF in the presence of autologous plasma, a rich source of age-specific soluble immunomodulatory factors (19), as described previously (23, 25). In response to Bexsero, a strong upregulation of CD80, HLA-DR (MHCII), and CCR7 and a modest increase in CD86 were observed in both newborn and adult DCs (Figures 3A,B).…”

Section: Resultsmentioning

confidence: 99%

“…Monocytes were cultured in tissue culture dishes at 0.4 × 10 6 cells/ml in RPMI media containing fresh 10% autologous platelet-poor plasma, supplemented with recombinant human (rh) IL-4 (50 ng/ml) and rh granulocyte-macrophage colony-stimulating factor (rhGM-CSF) (100 ng/ml) (R&D Systems, Minneapolis, MN, USA) with one replenishment of fresh media/cytokines at day 3. After 5–6 days, immature MoDCs were handled, as described previously (23, 25). …”

Section: Methodsmentioning

confidence: 99%

A Meningococcal Outer Membrane Vesicle Vaccine Incorporating Genetically Attenuated Endotoxin Dissociates Inflammation from Immunogenicity

et al. 2016

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BackgroundGroup B Neisseria meningitidis, an endotoxin-producing Gram-negative bacterium, causes the highest incidence of group B meningococcus (MenB) disease in the first year of life. The Bexsero vaccine is indicated in Europe from 8 weeks of age. Endotoxin components of outer membrane vesicles (OMVs) or soluble lipopolysaccharide (LPS) represent a potential source of inflammation and residual reactogenicity. The purpose of this study was to compare novel candidate MenB vaccine formulations with licensed vaccines, including Bexsero, using age-specific human in vitro culture systems.MethodsOMVs from wild type- and inactivated lpxL1 gene mutant-N. meningitidis strains were characterized in human neonatal and adult in vitro whole blood assays and dendritic cell (DC) arrays. OMVs were benchmarked against licensed vaccines, including Bexsero and whole cell pertussis formulations, with respect to Th-polarizing cytokine and prostaglandin E2 production, as well as cell surface activation markers (HLA-DR, CD86, and CCR7). OMV immunogenicity was assessed in mice.ResultsΔlpxLI native OMVs (nOMVs) demonstrated significantly less cytokine induction in human blood and DCs than Bexsero and most of the other pediatric vaccines (e.g., PedvaxHib, EasyFive, and bacillus Calmette–Guérin) tested. Despite a much lower inflammatory profile in vitro than Bexsero, ΔlpxLI nOMVs still had moderate DC maturing ability and induced robust anti-N. meningitidis antibody responses after murine immunization.ConclusionA meningococcal vaccine comprised of attenuated LPS-based OMVs with a limited inflammatory profile in vitro induces robust antigen-specific immunogenicity in vivo.

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“…In addition to influenza, PCPP could be combined with HIV antigens to form macromolecular complexes. In vivo , PCPP‐HIV Gag complexes activate more efficiently human dendritic cells (DCs) from adults and newborns and generate further cytokine production than the same antigen formulated with alum . PCPP complexed with HIV vaccine formulations [ALVAC‐HIV (vCP1521) primed with oligomeric gp160 (92TH023/LAI‐DID) or Bivalent gp120 (CM235/SF2) boost] were evaluated for immune responses and safety in clinical studies.…”

Section: Part II Use Of Ppzs For the Delivery Of Biomacromoleculesmentioning

confidence: 99%

Polyphosphazenes for the delivery of biopharmaceuticals

Hsu

Csaba

Alexander

et al. 2019

J of Applied Polymer Sci

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Polyphosphazenes (PPZs) are a relatively new family of polymers based on a nitrogen–phosphorous backbone where organic side groups can be grafted. The synthetic route to PPZs is highly versatile such that it is possible to add many different functionalities that change completely the physicochemical and biological properties of the polymers. For instance, PPZs can be designed with a variety of organic side groups that render these materials biodegradable and highly biocompatible. Based on these positive features, PPZs have been explored for many biomedical applications including the design of numerous advanced drug delivery systems. In this area, PPZs have been particularly investigated as materials for the formulation of biopharmaceuticals of high added value. These include protein‐ and polynucleotide‐based medicines, applications where PPZ carriers have obtained very positive results in preclinical models. A further area of major interest for PPZs has been vaccination, where these materials have obtained excellent results in vivo as polymer adjuvants and have advanced to clinical evaluation. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48688.

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The effect of stable macromolecular complexes of ionic polyphosphazene on HIV Gag antigen and on activation of human dendritic cells and presentation to T-cells

Cited by 33 publications

References 47 publications

TLR7/8 adjuvant overcomes newborn hyporesponsiveness to pneumococcal conjugate vaccine at birth

TLR7/8 adjuvant overcomes newborn hyporesponsiveness to pneumococcal conjugate vaccine at birth

A Meningococcal Outer Membrane Vesicle Vaccine Incorporating Genetically Attenuated Endotoxin Dissociates Inflammation from Immunogenicity

Polyphosphazenes for the delivery of biopharmaceuticals

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