Human immunodeficiency virus type-1-specific immune responses induced by DNA vaccination are greatly enhanced by mannan-coated diC14-amidine.

Use of mannan-coated N-t-butyl-N'-tetradecyl-3-tetradecylamino-propionamidine (diC14-amidine) as an adjuvant for a DNA vaccine encoding glycoprotein 160 of human immunodeficiency virus type-1 (HIV-1) enhanced the antigen-specific immune responses. The role of interferon-gamma (IFN-gamma) and interleukin-12 in the mechanism of adjuvant action was also evaluated. Coating of diC14-amidine with mannan significantly augmented the HIV-specific delayed-type hypersensitivity reaction induced by the immunogenic DNA. HIV-1-specific cytotoxic T lymphocyte activity was also markedly enhanced by the mannan-diC14-amidine cocktail. An immunomodulatory effect of this cocktail was inhibited by treatment with anti-IFN-gamma monoclonal antibody in vivo, which suggests that IFN-gamma plays an important role in inducing cell-mediated immunity by the DNA vaccine containing this adjuvant. The results of both antigen-specific immunoglobulin isotype analysis and cytokine measurement showed that the immunogenic DNA incorporated into mannan-coated diC14-amidine elicits Th1-biased immune responses.Journal ArticleResearch Support, Non-U.S. Gov'tFLWINinfo:eu-repo/semantics/publishe

Identification of peptides derived from the human antimicrobial peptide LL-37 active against the biofilms formed by Pseudomonas aeruginosa using a library of truncated fragments.

Persistent Pseudomonas aeruginosa infections are a major cause of morbidity and mortality in CF patients and are linked to the formation of a biofilm. The development of new biofilm inhibition strategies is thus a major challenge. LL-37 is the only human antimicrobial peptide derived from cathelicidin. The effects on the P. aeruginosa PAO1 strain of synthetic truncated fragments of this peptide were compared with the effects of the original peptide. Fragments of LL-37 composed of 19 residues (LL-19, LL13-31 and LL7-25) inhibited biofilm formation. The strongest antibiofilm activity was observed with the peptides LL7-37 and LL-31, which decreased the percentage of biomass formation at a very low concentration. Some peptides were also active on the bacteria within an established biofilm. LL7-31, LL-31 and LL7-37 increased the uptake of PI by sessile bacteria. The peptide LL7-37 decreased the height of the biofilm and partly disrupted it. The peptides active within the biofilm had an infra-red spectrum compatible with an α-helix. LL-37, but not the peptides LL7-31 and LL7-37, showed cellular toxicity by permeabilizing the eukaryotic plasma membrane (uptake of ethidium bromide and release of LDH). None of the tested peptides affected mitochondrial activity in eukaryotic cells.In conclusion, a 25 amino acid peptide (LL7-31) displayed both strong antimicrobial and antibiofilm activity. The peptide was even active on cells within a preformed biofilm and had reduced toxicity towards eukaryotic cells. Our results also suggest the contribution of secondary structures (α-helix) to the activity of the peptides on biofilms.JOURNAL ARTICLESCOPUS: ar.jinfo:eu-repo/semantics/publishe