Modulation of immune responses using adjuvants to facilitate therapeutic vaccination.

Therapeutic vaccination offers great promise as an intervention for a diversity of infectious and non-infectious conditions. Given that most chronic health conditions are thought to have an immune component, vaccination can at least in principle be proposed as a therapeutic strategy. Understanding the nature of protective immunity is of vital importance, and the progress made in recent years in defining the nature of pathological and protective immunity for a range of diseases has provided an impetus to devise strategies to promote such responses in a targeted manner.

Biofilm infections between Scylla and Charybdis: interplay of host antimicrobial peptides and antibiotics.

Purpose: The aim of this study is to improve the anti-biofilm activity of antibiotics. We hypothesized that the antimicrobial peptide (AMP) complex of the host's immune system can be used for this purpose and examined the assumption on model biofilms.

Methods: FLIP7, the AMP complex of the blowfly containing a combination of defensins, cecropins, diptericins and proline-rich peptides was isolated from the hemolymph of bacteria-challenged maggots.

Natural antimicrobial peptide complexes in the fighting of antibiotic resistant biofilms: Calliphora vicina medicinal maggots.

Biofilms, sedimented microbial communities embedded in a biopolymer matrix cause vast majority of human bacterial infections and many severe complications such as chronic inflammatory diseases and cancer. Biofilms' resistance to the host immunity and antibiotics makes this kind of infection particularly intractable. Antimicrobial peptides (AMPs) are a ubiquitous facet of innate immunity in animals.

Fat body and hemocyte contribution to the antimicrobial peptide synthesis in Calliphora vicina R.-D. (Diptera: Calliphoridae) larvae.

Antimicrobial peptides accumulated in the hemolymph in response to infection are a key element of insect innate immunity. The involvement of the fat body and hemocytes in the antimicrobial peptide synthesis is widely acknowledged, although release of the peptides present in the hemolymph from the immune cells was not directly verified so far. Here, we studied the presence of antimicrobial peptides in the culture medium of fat body cells and hemocytes isolated from the blue blowfly Calliphora vicina using complex of liquid chromatography, mass spectrometry, and antimicrobial activity assays.

Insect Antimicrobial Peptide Complexes Prevent Resistance Development in Bacteria.

In recent decades much attention has been paid to antimicrobial peptides (AMPs) as natural antibiotics, which are presumably protected from resistance development in bacteria. However, experimental evolution studies have revealed prompt resistance increase in bacteria to any individual AMP tested. Here we demonstrate that naturally occurring compounds containing insect AMP complexes have clear advantage over individual peptide and small molecule antibiotics in respect of drug resistance development.

Anti-tumor activity of a peptide combining patterns of insect alloferons and mammalian immunoglobulins in naïve and tumor antigen vaccinated mice.

Alloferons are a group of naturally occurring peptides primarily isolated from insects and capable of stimulating mouse and human NK cell cytotoxicity towards cancer cells. In this paper we examined anti-tumor activity of alloferon-1 and its novel structural analog referred to as allostatine. The activity was tested in naïve and preventively tumor antigen vaccinated DBA/2 mice subcutaneously grafted with syngenic P388D1 mouse leukemia cells.

Anti-tumor activity of immunomodulatory peptide alloferon-1 in mouse tumor transplantation model.

Alloferons are a group of antiviral and anti-tumor peptides primarily isolated from insects and stimulating cytotoxic activity of natural killer cells in mammals including mice and humans. Alloferon-1 is currently used in the treatment of persistent viral infections; however its anti-tumor potential needs further preclinical assessment. Here we evaluate alloferon-1 anti-tumor activity in DBA/2 mice grafted with syngenic P388 murine leukemia cells.

Activation of NF-kappaB by alloferon through down-regulation of antioxidant proteins and IkappaBalpha.

Alloferon is a 13-amino acid peptide isolated from the bacteria-challenged larvae of the blow fly Calliphora vicina. The pharmaceutical value of the peptide has been well demonstrated by its capacity to stimulate NK cytotoxic activity and interferon (IFN) synthesis in animal and human models, as well as to enhance antiviral and antitumor activities in mice. Antiviral and the immunomodulatory effectiveness of alloferon have also been supported clinically proved in patients suffering with herpes simplex virus (HSV) and human papilloma virus (HPV) infections.

Cytotoxic activity of blowfly Calliphora vicina hemocytes.

The cytotoxic activity of hemocytes isolated from larvae of the blowfly Calliphora vicina was tested using human myelogenous leukemia K562 cells as target. Both single cell and cytotoxicity assays demonstrated that the hemocytes recognize the K562 cells as nonself, firmly attach to their surface and induce target destruction in a manner resembling the effect of mammalian cytotoxic lymphocytes. The cytotoxic activity increased dramatically in the course of larval metamorphosis and was considerably higher shortly before the onset of pupariation, compared to the activity of human peripheral blood or mouse spleen lymphocytes.

Antiviral and antitumor peptides from insects.

Insects can rapidly clear microbial infections by producing a variety of immune-induced molecules including antibacterial and/or antifungal peptides/polypeptides. In this report, we present the isolation, structural characterization, and biological properties of two variants of a group of bioactive, slightly cationic peptides, referred to as alloferons. Two peptides were isolated from the blood of an experimentally infected insect, the blow fly Calliphora vicina (Diptera), with the following amino acid sequences: HGVSGHGQHGVHG (alloferon 1) and GVSGHGQHGVHG (alloferon 2).