Memory T-cell immune response in healthy young adults vaccinated with live attenuated influenza A (H5N2) vaccine

Cellular immune responses of both CD4 and CD8 memory/effector T cells were evaluated in healthy young adults who received two doses of live attenuated influenza A (H5N2) vaccine. The vaccine was developed by reassortment of nonpathogenic avian A/Duck/Potsdam/1402-6/68 (H5N2) and cold-adapted A/Leningrad/134/17/57 (H2N2) viruses. T-cell responses were measured by standard methods of intracellular cytokine staining of gamma interferon (IFN-γ)-producing cells and a novel T-cell recognition of antigen-presenting cells by protein capture (TRAP) assay based on the trogocytosis phenomenon, namely, plasma membrane exchange between interacting immune cells. TRAP enables the detection of activated trogocytosis-positive T cells after virus stimulation. We showed that two doses of live attenuated influenza A (H5N2) vaccine promoted both CD4 and CD8 T-memory-cell responses in peripheral blood of healthy young subjects in the clinical study. Significant differences in geometric mean titers (GMTs) of influenza A (H5N2)-specific IFN-γ + cells were observed at day 42 following the second vaccination, while peak levels of trogocytosis + T cells were detected earlier, on the 21st day after the second vaccination. The inverse correlation of baseline levels compared to postvaccine fold changes in GMTs of influenza-specific CD4 and CD8 T cells demonstrated that baseline levels of these specific cells could be considered a predictive factor of vaccine immunogenicity. Copyright © 2011, American Society for Microbiology. All Rights Reserved

Design, synthesis, antibacterial activity and toxicity of novel quaternary ammonium compounds based on pyridoxine and fatty acids

A diverse series of 43 novel “soft antimicrobials” based on quaternary ammonium pyridoxine derivatives which include six-membered acetals and ketals of pyridoxine bound via cleavable linker moieties (amide, ester) with a fragment of fatty carboxylic acid was designed. Nine compounds exhibited in vitro promising antibacterial activity against Gram-positive and Gram-negative bacterial strains with MIC values comparable with reference antiseptics miramistin, benzalkonium chloride and chlorohexidine. On various clinical isolates, the lead compounds 6i and 12a exhibited antibacterial activity comparable with that of benzalkonium chloride while higher than that of miramistin. Moreover, 6i and 12a were able to kill bacteria embedded into the matrix of mono- and dual species biofilms. The treatment of bacterial cells by either 6i and 12a lead to fast depolarization of the membrane suggesting that the membrane is an apparent molecular target of compounds. 6i and 12a were non mutagenic neither in SOS-chromotest nor in Ames test and non-toxic in vivo at acute oral (LD50 > 2000 mg/kg) and cutaneous administration (LD50 > 2500 mg/kg) on mice. Taken together, our data allow suggesting described active compounds as promising starting point for the new antibacterial agents development

Anti-biofilm and wound-healing activity of chitosan-immobilized Ficin

© 2020 Biofouling is among the key factors slowing down healing of acute and chronic wounds. Here we report both anti-biofilm and wound-healing properties of the chitosan-immobilized Ficin. The proposed chitosan-adsorption approach allowed preserving ~90% of the initial total activity of the enzyme (when using azocasein as a substrate) with stabilization factor of 4.9, and ~70% of its specific enzymatic activity. In vitro, the chitosan-immobilized Ficin degraded staphylococcal biofilms, this way increasing the efficacy of antimicrobials against biofilm-embedded bacteria. In vivo, in the presence of Ficin (either soluble or immobilized), the S.aureus-infected skin wound areas in rats reduced twofold after 4 instead of 6 days treatment. Moreover, topical application of the immobilized enzyme resulted in a 3-log reduction of S. aureus cell count on the wound surfaces in 6 days, compared to more than 10 days required to achieve the same effect in control. Additional advantages include smoother reepithelisation, and new tissue formation exhibiting collagen structure characteristics closely reminiscent of those observed in the native tissue. Taken together, our data suggest that both soluble and immobilized Ficin appear beneficial for the treatment of biofilm-associated infections, as well as speeding up wound healing and microbial decontamination