Water-soluble form of fullerene C60 is a promising tool for the control of ROS-dependent inflammation including allergic diseases. Anti-inflammatory effects of C60 (nC60) aqueous dispersion were evaluated in the mouse models of atopic dermatitis using subcutaneous (SC) and epicutaneous (EC) applications during 50 days period. A highly stable nC60 was prepared by exhaustive dialysis of water-organic C60 solution against water, where the size and ζ-potential of fullerene nanoparticles are about 100 nm and −30 mV, respectively. To induce skin inflammation, female BALB/c mice were EC sensitized with ovalbumin three times during one-weekly exposures. The nC60 solution was administrated in mice subcutaneously (SC) (0.1 mg/kg) and epicutaneously (EC) (1 mg/kg). Significant suppression of IgE and Th2 cytokines production and a concomitant rise in concentrations of Th1 cytokines were observed in nC60-treated groups. In addition, a significant increase in the levels of Foxp3+ and filaggrin mRNA expression was observed at EC application. Histological examination of skin samples indicated that therapeutic effect was achieved by both EC and SC treatment, but it was more effective with EC. Pronounced reduction of the eosinophil and leukocyte infiltration in treated skin samples was observed. We suppose that nC60 treatment shifts immune response from Th2 to Th1 and restores to some extent the function of the skin barrier. This approach can be a good alternative to the treatment of allergic and other inflammatory diseases.

Background: The nature of epitopes on Bet v 1 recognized by natural IgG antibodies of birch pollen allergic patients and birch pollen‐exposed but non‐sensitized subjects has not been studied in detail.Objective: To investigate IgE and IgG recognition of Bet v 1 and to study the effects of natural Bet v 1‐specific IgG antibodies on IgE recognition of Bet v 1 and Bet v 1‐induced basophil activation.Methods: Sera from birch pollen allergic patients (BPA, n = 76), allergic patients without birch pollen allergy (NBPA, n = 40) and non‐allergic individuals (NA, n = 48) were tested for IgE, IgG as well as IgG₁ and IgG₄ reactivity to folded recombinant Bet v 1, two unfolded recombinant Bet v 1 fragments comprising the N‐terminal (F1) and C‐terminal half of Bet v 1 (F2) and unfolded peptides spanning the corresponding sequences of Bet v 1 and the apple allergen Mal d 1 by ELISA or micro‐array analysis. The ability of Bet v 1‐specific serum antibodies from non‐allergic subjects to inhibit allergic patients IgE or IgG binding to rBet v 1 or to unfolded Bet v 1‐derivatives was assessed by competition ELISAs. Furthermore, the ability of serum antibodies from allergic and non‐allergic subjects to modulate Bet v 1‐induced basophil activation was investigated using rat basophilic leukaemia cells expressing the human FcεRI which had been loaded with IgE from BPA patients.Results: IgE antibodies from BPA patients react almost exclusively with conformational epitopes whereas IgG, IgG₁ and IgG₄ antibodies from BPA, NBPA and NA subjects recognize mainly unfolded and sequential epitopes. IgG competition studies show that IgG specific for unfolded/sequential Bet v 1 epitopes is not inhibited by folded Bet v 1 and hence the latter seem to represent cryptic epitopes. IgG reactivity to Bet v 1 peptides did not correlate with IgG reactivity to the corresponding Mal d 1 peptides and therefore does not seem to be a result of primary sensitization to PR10 allergen‐containing food. Natural Bet v 1‐specific IgG antibodies inhibited IgE binding to Bet v 1 only poorly and could even enhance Bet v 1‐specific basophil activation.Conclusion: IgE and IgG antibodies from BPA patients and birch pollen‐exposed non‐sensitized subjects recognize different epitopes. These findings explain why natural allergen‐specific IgG do not protect against allergic symptoms and suggest that allergen‐specific IgE and IgG have different clonal origin.

An arginine-rich peptide dendrimer, LTP, is a new low-toxicity promising tool for intracellular gene delivery.

Atopic dermatitis (AD) is a widespread and difficult to treat allergic skin disease and is a tough challenge for healthcare. In this study, we investigated whether allergen-specific immunotherapy (ASIT) with a monomeric allergoid obtained by succinylation of ovalbumin (sOVA) is effective in a mouse model of atopic dermatitis. An experimental model of AD was reproduced by epicutaneous sensitization with ovalbumin (OVA). ASIT was performed with subcutaneous (SC) administration of increasing doses of OVA or sOVA. The levels of anti-OVA antibodies, as well as cytokines, were detected by ELISA. Skin samples from patch areas were taken for histologic examination. ASIT with either OVA or sOVA resulted in a reduction of both the anti-OVA IgE level and the IgG1/IgG2a ratio. Moreover, ASIT with sOVA increased the IFN-γ level in supernatants after splenocyte stimulation with OVA. Histologic analysis of skin samples from the sites of allergen application showed that ASIT improved the histologic picture by decreasing allergic inflammation in comparison with untreated mice. These data suggest that ASIT with a succinylated allergen represents promising approach for the treatment of AD.

Respiratory syncytial virus (RSV) is one of the most common viral pathogens. It is especially dangerous for newborns and young children. In some cases it could lead to severe bronchiolitis, pneumonia with hospitalization or even a lethal outcome. Despite decades of investigation of RSV biology, effective and safe therapeutics are still under development. Certain natural peptides have been found to exhibit antiviral activity against respiratory viruses, but their implementation is limited by low stability in biological media. One of the current approaches to enhance the peptide therapeutic opportunities is chemical synthesis of peptide dendrimers with hyperbranched structures. Taking into account the recent data of bioactive cationic and helical regions of natural peptides and the structure features of nucleolin identified as an RSV cellular receptor, the main goal of this study was to design relatively short linear and dendrimeric cationic peptides and to test their antiviral activity against RSV. As a result 3 linear cationic peptides and 4 peptide dendrimers were synthesized and compared with known LL-37 (cathelicidin family) and anti-F0 monoclonal antibodies in terms of cytotoxicity and antiviral activity. Their affinity to the supposed molecular target – nucleolin (C23) – was estimated in silico by molecular docking analysis. Four synthesized peptides demonstrated a cytotoxic effect, two of them were even more cytotoxic than LL-37, which could be explained by a combination of a high amount of positive charge and amphipathicity. Contrariwise, non-hydrophobic dendrimer peptides did not exhibit cytotoxicity in mammalian cells in the studied concentration range. Two of the seven synthesized peptides, LTP (dendrimer) and SA-35 (linear), used in this study had a stronger antiviral effect than natural peptide LL-37, and three others showed slightly lower activity than anti-F0 monoclonal antibodies. The data obtained in this study suggest that evenly distributed positive charge, and low or medium amphipathicity play a key role in the antiviral activity of the studied peptides. Moreover, the calculated free energy values of the peptide/nucleolin complex for the most active peptides supported the idea that the peptide ability of nucleolin interaction promotes the anti-RSV properties of the molecules.

Fullerene C₆₀ is known as a promising therapeutic agent due to its antioxidant, anti-inflammatory and other properties, along with the lack of noticeable toxicity. In this article, we describe antiviral properties of aqueous fullerene C₆₀ dispersion (ndC₆₀) produced by biocompatible diafiltration technology and C₆₀ amino derivatives against Herpes simplex virus type 1 (HSV-1) and Human cytomegalovirus (HCMV) infections. Their activity in vitro was evaluated by a plaque reduction assay using Vero and HF cells in pre- and post-treatment modes. Therapeutic efficacy of dnC₆₀ and C₆₀ derivatives was studied in DBA mice using cutaneous model of HSV-1 infection. Data obtained indicated low cytotoxicity of all used compounds for both cell lines (CC₅₀ > 1 mg/ml). The antiviral activity of dnC₆₀ in most tests exceeded the activity of both C₆₀ amino adducts and acyclovir (ACV), and it demonstrated significant therapeutic effect against HSV-1 skin infection in mice.