Proxima Concepts Ltd

Bodle Street, United Kingdom

Proxima Concepts Ltd

Bodle Street, United Kingdom
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Andrade G.R.,Instituto Butantan | New R.R.C.,Proxima Concepts Ltd | Sant'Anna O.A.,Instituto Butantan | Williams N.A.,University of Bristol | And 8 more authors.
Human Vaccines and Immunotherapeutics | Year: 2014

E. coli O111 strains are responsible for outbreaks of blood diarrhea and hemolytic uremic syndrome throughout the world. Because of their phenotypic variability, the development of a vaccine against these strains which targets an antigen that is common to all of them is quite a challenge. Previous results have indicated, however, that O111 LPS is such a candidate, but its toxicity makes LPS forbidden for human use. To overcome this problem, O111 polysaccharides were conjugated either to cytochrome C or to EtxB (a recombinant B subunit of LT) as carrier proteins. The O111-cytochrome C conjugate was incorporated in silica SBA-15 nanoparticles and administered subcutaneously in rabbits, while the O111-EtxB conjugate was incorporated in Vaxcine™, an oil-based delivery system, and administered orally in mice. The results showed that one year post-vaccination, the conjugate incorporated in silica SBA-15 generated antibodies in rabbits able to inhibit the adhesion of all categories of O111 E. coli to epithelial cells. Importantly, mice immunized orally with the O111-EtxB conjugate in Vaxcine™ generated systemic and mucosal humoral responses against all categories of O111 E. coli as well as antibodies able to inhibit the toxic effect of LT in vitro. In summary, the results obtained by using 2 different approaches indicate that a vaccine that targets the O111 antigen has the potential to prevent diarrhea induced by O111 E. coli strains regardless their mechanism of virulence. They also suggest that a conjugated vaccine that uses EtxB as a carrier protein has potential to combat diarrhea induced by ETEC. © 2014 Taylor & Francis Group, LLC.


New R.,Proxima Concepts Ltd | New R.,Bone Medical Ltd | Bansal G.S.,Proxima Concepts Ltd | Dryjska M.,Proxima Concepts Ltd | And 4 more authors.
Molecules | Year: 2014

Although strong binding interactions between protein receptor and ligand do not require the participation of a large number of amino acids in either site, short peptide chains are generally poor at recreating the types of protein-protein interactions which take place during cell recognition and signalling process, probably because their flexible backbones prevent the side chains from forming sufficiently rigid and stable epitopes, which can take part in binding with the desired strength and specificity. In a recently-reported study, it was shown that a proto-epitope containing F, R and S amino acids has the ability to down-regulate TNF secretion by macrophages. This paper extends these findings, putting those amino acids into a short cyclic peptide scaffold, and determining the optimal configuration required to overcome the problems of conformational instability, and give rise to molecules which have potential as therapeutic agents in human disease, such as rheumatoid arthritis. © 2014 by the authors; licensee MDPI, Basel, Switzerland.


New R.,Proxima Concepts Ltd | New R.,Bone Medical Ltd | Bansal G.S.,Proxima Concepts Ltd | Bogus M.,Proxima Concepts Ltd | And 4 more authors.
Molecules | Year: 2013

We describe a new method of combinatorial screening in which building blocks, instead of being linked together chemically, are placed on the surface of nanoparticles. Two- or three-dimensional structures form on the surface of these particles through the close approach of different building blocks, with sufficient flexibility to be able to adapt and interact with putative binding sites in biological systems. The particles assemble without the need for formation of chemical bonds, so libraries comprised of many structures can be prepared rapidly, with large quantities of material available for testing. Screening methods can include solid and solution-phase binding assays, or tissue culture models, for example looking for structures which can change the behaviour of cells in a disease-modifying manner.


Ziora Z.M.,University of Queensland | Wimmer N.,University of Queensland | New R.,Proxima Concepts Ltd | Skwarczynski M.,University of Queensland | Toth I.,University of Queensland
Carbohydrate Research | Year: 2011

A class of glycolipopeptides for use as building blocks for a new type of dynamic combinatorial library is reported. The members of the library consist of a variable carbohydrate moiety, coded amino acids, and lipoamino acids in order to convert them into amphiphiles. Glycolipopeptidic amphiphiles interact through non-covalent bonding when mixed together in aqueous phase and form micelles in dynamic close-packed fluid mosaic arrays. The head groups of amphiphiles are exposed on the micelle surface, providing entities which could be screened in biological assays to find the most potent combination of building blocks in order to identify new bioactive carbohydrate ligands. © 2011 Elsevier Ltd. All rights reserved.


Wang S.X.,Middlesex University | Michiels J.,Institute of Tropical Medicine | Arien K.K.,Institute of Tropical Medicine | New R.,Proxima Concepts. Ltd | And 2 more authors.
Nanoscale Research Letters | Year: 2016

Although highly active antiretroviral therapy (HAART) has greatly improved the life expectancy of HIV/AIDS patients, the treatment is not curative. It is a global challenge which fosters an urgent need to develop an effective drug or neutralizing antibody delivery approach for the prevention and treatment of this disease. Due to the low density of envelope spikes with restricted mobility present on the surface of HIV virus, which limit the antibody potency and allow virus mutation and escape from the immune system, it is important for a neutralizing antibody to form bivalent or multivalent bonds with the virus. Liposome constructs could fulfil this need due to the flexible mobility of the membrane with its attached antibodies and the capacity for drug encapsulation. In this study, we evaluated the neutralization activity of a range of liposome formulations in different sizes coated with anti-gp120 llama antibody fragments (Vhhs) conjugated via either non-covalent metal chelation or a covalent linkage. The non-covalent construct demonstrated identical binding affinity to HIV-1 envelope glycoprotein gp120 and neutralizing ability for HIV virus as free Vhh. Although covalently linked Vhh showed significant binding affinity to gp120, it unexpectedly had a lower neutralization potency. This may be due to the comparability in size of the viral and liposome particles restricting the number which can be bound to the liposome surface so involving only a fraction of the antibodies, whereas non-covalently attached antibodies dissociate from the surface after acting with gp120 and free the remainder to bind further viruses. Covalently conjugated Vhh might also trigger the cellular uptake of a liposome-virion complex. To explore the possible ability of the antibody-coated liposomes to have a further function, we encapsulated the hydrophobic antiviral drug dapivirine into both of the non-covalently and covalently conjugated liposome formulations, both of which revealed high efficacy in reducing viral replication in vitro. Thus, dual function liposomes may lead to a novel strategy for the prophylaxis of HIV/AIDS by combining the neutralizing activity of Vhh with antiviral effects of high drug concentrations. © 2016, The Author(s).


PubMed | Proxima Concepts Ltd
Type: Journal Article | Journal: Molecules (Basel, Switzerland) | Year: 2013

We describe a new method of combinatorial screening in which building blocks, instead of being linked together chemically, are placed on the surface of nanoparticles. Two- or three-dimensional structures form on the surface of these particles through the close approach of different building blocks, with sufficient flexibility to be able to adapt and interact with putative binding sites in biological systems. The particles assemble without the need for formation of chemical bonds, so libraries comprised of many structures can be prepared rapidly, with large quantities of material available for testing. Screening methods can include solid and solution-phase binding assays, or tissue culture models, for example looking for structures which can change the behaviour of cells in a disease-modifying manner.


Grant
Agency: GTR | Branch: Innovate UK | Program: | Phase: Small Business Research Initiative | Award Amount: 495.00K | Year: 2016

The objective of this proposal is to develop a technology platform for producing safe, temperature-stable vaccines for global diseases. A particular focus will be self-administered delivery by oral vaccination because this can be carried out efficiently in resource-poor settings and is highly desirable to prevent serious endemic diseases in at-risk populations. Using our innovative oral vaccine formulation technology, we intend to formulate recombinant protective antigens to protect against the serious diseases of MERS and plague for which no licensed vaccines currently exist. The applicant, Proxima Concepts Ltd, will supplement its in-house formulation expertise with input from contracted partners that have state-of-the-arts capabilities in recombinant antigen production, preclinical vaccine testing (DSTL), protein antigen stabilisation and formulation (University of Strathclyde). This combined expertise will enable us to demonstrate the scientific and technical feasibility of developing a candidate vaccine for each of the indications over the 12 months of the project. In addition the project is designed to generate sufficient pre-clinical data to support the planned transition towards clinical development. The basic concept for these vaccines is that an injected priming dose would be administered by trained medical personnel in a health centre. The patient would then return home and subsequently self-administer the boost(s) by taking an enteric-coated capsule containing an oral formulation of the same vaccine This programme of work will produce stable vaccine formulations which can be rapidly and cost-effectively manufactured in an emergency situation and quickly deployed in potential epidemic areas. The combination of an injected prime and oral boost is an innovative approach to vaccines for prevention of respiratory infections but could potentially provide a platform for protecting against other epidemic diseases.

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