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Groningen, Netherlands

Nganou-Makamdop K.,Radboud University Nijmegen | Van Roosmalen M.L.,Mucosis BV | Audouy S.A.,BiOMaDe Technology Foundation | Van Gemert G.-J.,Radboud University Nijmegen | And 3 more authors.
Malaria Journal | Year: 2012

Background: Virus-like particles have been regularly used as an antigen delivery system for a number of Plasmodium peptides or proteins. The present study reports the immunogenicity and protective efficacy of bacterium-like particles (BLPs) generated from Lactococcus lactis and loaded with Plasmodium berghei circumsporozoite protein (PbCSP) peptides. Methods. A panel of BLP-PbCSP formulations differing in composition and quantity of B-cell, CD4+ and CD8+ T-cell epitopes of PbCSP were tested in BALB/c mice. Results: BLP-PbCSP1 induced specific humoral responses but no IFN- ELISPOT response, protecting 30-40% of the immunized mice. BLP-PbCSP2, with reduced length of the non-immunogenic part of the T-cell-epitopes construct, increased induction of IFN- responses as well as protection up to 60-70%. Compared to controls, lower parasitaemia was observed in unprotected mice immunized with BLP-PbCSP1 or 2, suggestive for partial immunity. Finally, further increase of the number of B-cell epitopes and codon optimization (BLP-PbCSP4) induced the highest anti-CSP antibody levels and number of IFN- spots, resulting in sterile immunity in 100% of the immunized mice. Conclusion: Presentation of Plasmodium-derived antigens using BLPs as a delivery system induced complete protection in a murine malaria model. Eventually, BLPs have the potential to be used as a novel versatile delivery platform in malaria vaccine development. © 2012 Nganou-Makamdop et al; licensee BioMed Central Ltd.

Durik M.,Erasmus Medical Center | Van Veghel R.,Erasmus Medical Center | Kuipers A.,LanthioPep | Rink R.,LanthioPep | And 5 more authors.
International Journal of Hypertension | Year: 2012

Modulation of renin-angiotensin system (RAS) by angiotensin-(17) (Ang-(17)) is an attractive approach to combat the detrimental consequences of myocardial infarction (MI). However Ang-(17) has limited clinical potential due to its unfavorable pharmacokinetic profile. We investigated effects of a stabilized, thioether-bridged analogue of Ang-(17) called cyclic Ang-(17) in rat model of myocardial infarction. Rats underwent coronary ligation or sham surgery. Two weeks thereafter infusion with 0.24 or 2.4 μg/kg/h cAng-(17) or saline was started for 8 weeks. Thereafter, cardiac morphometric and hemodynamic variables as wells as aortic endothelial function were measured. The average infarct size was 13.8 and was not changed by cAng-(17) treatment. MI increased heart weight and myocyte size, which was restored by cAng-(17) to sham levels. In addition, cAng-(17) lowered left ventricular end-diastolic pressure and improved endothelial function. The results suggest that cAng-(17) is a promising new agent in treatment of myocardial infarction and warrant further research. © 2012 Matej Durik et al.

Kocer A.,BiOMaDe Technology Foundation | Kocer A.,University of Groningen | Tauk L.,Montpellier University | Dejardin P.,Montpellier University
Biosensors and Bioelectronics | Year: 2012

The use of nanopores of well controlled geometry for sensing molecules in solution is reviewed. Focus is concentrated especially on synthetic track-etch pores in polymer foils and on biological nanopores, i.e. ion channels. After a brief section about multipore sensors, specific attention is provided to works relative to a single nanopore sensor. The different strategies to combine the robustness of supports with the high selectivity of the biological channels are reviewed. The scope ranges from keeping the membrane natural environment of biological channels in supported and suspended bilayer membranes, to considering completely abiotic designed nanopores created through synthetic materials. The α-hemolysine channel and the mechanosensitive channel of large conductance with their modifications are especially considered in the first strategy, the conical functionalized nanopores created in polymer foils in the second one. The different attempts of reading macromolecules are also discussed. A third hybrid strategy, which was not extensively explored, consists in the inclusion of a biological structure into a well-designed nanopore through the support, as recently with gramicidin. © 2012 Elsevier B.V.

Plat A.,BiOMaDe Technology Foundation | Kuipers A.,Lanthio Pharma | Rink R.,Lanthio Pharma | Moll G.N.,Lanthio Pharma
Current Protein and Peptide Science | Year: 2013

Lanthipeptides are ribosomally synthesized and posttranslationally modified peptides produced by microorganisms. The name lanthipeptide is derived from lanthionine, a thioether-bridged amino acid installed by dedicated modification enzymes. Serines and threonines are dehydrated and subsequently coupled to cysteines, thus forming intramolecular lanthionine rings. A well-known subclass of lanthipeptides are lantibiotics: lanthipeptides with antimicrobial activity. The lantibiotic nisin is applied worldwide in the food industry to prevent food spoilage. This review focuses on lanthipeptide leader peptides, which have a crucial and central role in lanthipeptide biosynthesis. Lanthipeptide leader peptides are present at the N-terminus within precursor lanthipeptides. Intriguingly, a single leader peptide can interact with highly different modifying enzyme(s) (domains) and furthermore induce export out of the cell via a dedicated export protein. Eventually the leader peptide is cleaved off by a leader peptidase, either extracellularly or intracellularly as part of the transporter. Recent exciting mechanistic and engineering studies ignited the unraveling of the fascinating interactions of lanthipeptide leader peptides with the lanthipeptide modification enzymes and transporters. The biosynthesis of at least some lanthipeptides is performed by a highly flexible enzyme system. Novel lantibiotics can be synthesized by fusing lanthipeptide leader peptides to completely different silent lantibiotics obtained by genome mining. Moreover, the fusion of leader peptides to the N-terminus of medically and economically important therapeutic peptides has resulted in lanthioninestabilized therapeutics with enhanced bioavailability and optimized receptor interaction. © 2013 Bentham Science Publishers.

Kusters I.,University of Groningen | Mukherjee N.,University of Groningen | de Jong M.R.,BiOMaDe Technology Foundation | Tans S.,FOM Institute for Atomic and Molecular Physics | And 2 more authors.
PLoS ONE | Year: 2011

Single molecule studies on membrane proteins embedded in their native environment are hampered by the intrinsic difficulty of immobilizing elastic and sensitive biological membranes without interfering with protein activity. Here, we present hydrogels composed of nano-scaled fibers as a generally applicable tool to immobilize biological membrane vesicles of various size and lipid composition. Importantly, membrane proteins immobilized in the hydrogel as well as soluble proteins are fully active. The triggered opening of the mechanosensitive channel of large conductance (MscL) reconstituted in giant unilamellar vesicles (GUVs) was followed in time on single GUVs. Thus, kinetic studies of vectorial transport processes across biological membranes can be assessed on single, hydrogel immobilized, GUVs. Furthermore, protein translocation activity by the membrane embedded protein conducting channel of bacteria, SecYEG, in association with the soluble motor protein SecA was quantitatively assessed in bulk and at the single vesicle level in the hydrogel. This technique provides a new way to investigate membrane proteins in their native environment at the single molecule level by means of fluorescence microscopy. © 2011 Kusters et al.

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