Ling Y.,China Agricultural University |
Liu W.,China Agricultural University |
Clark J.R.,Big DNA Co. |
March J.B.,Big DNA Co. |
And 2 more authors.
Veterinary Immunology and Immunopathology | Year: 2011
A bacteriophage-delivered DNA vaccine against Chlamydophila abortus was constructed by cloning a eukaryotic cassette containing the ompA gene (which expresses the Major Outer Membrane Protein) into a bacteriophage lambda vector. Four groups, each of 20 BALB/c mice were inoculated separately with the phage vaccine, a conventional DNA vaccine based on the same ompA expression cassette, a live attenuated vaccine (strain 1B) or the empty phage vector. The phage and DNA vaccines and empty phage vector were administered intramuscularly on days 0, 14 and 28; the attenuated vaccine was given once on day 0. Half the animals in each group were challenged on day 42 by intraperitoneal injection of live C. abortus and sacrificed on day 49. Phage-vaccinated mice developed moderate antibody levels against C. abortus and yielded higher levels of IFN-γ and IL-2 compared with the attenuated live vaccine group. Clearance of chlamydiae from spleens was significantly better in the attenuated vaccine group compared with the phage vaccine group, while both groups were significantly superior to the DNA vaccine and control groups (p< 0.01). Although levels of protection in the mouse model were lower in phage-vaccinated animals, than in 1B vaccinated animals, phage vaccines offer several other advantages, such as easier handling and safety, potentially cheaper production and no chance of reversion to virulence. Although these are preliminary results in a model system, it is possible that with further optimisation immunization with phage vaccines may provide a novel way to improve protection against C. abortus infection and trials in large animals are currently being initiated. © 2011 Elsevier B.V.
Agency: European Commission | Branch: FP7 | Program: CP-TP | Phase: KBBE.2012.1.2-10 | Award Amount: 8.06M | Year: 2012
European aquaculture production provides direct employment to 65.000 people with a turnover of 3 billion . However, the lack of authorised veterinary medicinal products and the consequent disease outbreaks in farmed fish species costs the sector 20% of the production value. The most appropriate method for disease control, both on economical and ethical grounds, is disease prevention by vaccination. TargetFish will advance the development of existing (but not sufficient) and new prototype vaccines against socio-economically important viral or bacterial pathogens of Atlantic salmon, rainbow trout, common carp, sea bass, sea bream and turbot. The project will develop targeted vaccination strategies for currently sub-optimal and for novel vaccines. Improved vaccines will be brought closer to industrial application by addressing practical issues such as efficacy, safety and delivery route. TargetFish will also establish a knowledge- and technology-base for rational development of next generation fish vaccines. To achieve these challenging tasks, we brought together 29 partners from 11 EU member states, 2 associated countries and 1 International Cooperation Partner Country (ICPC). In this large multidisciplinary consortium an approximate equal number of RTD and SME partners will cooperate closely while keeping an intensive communication with the large vaccine and nutrition industries via an Industry Forum. Specifically, TargetFish will 1) generate knowledge by studying antigens and adjuvants for mucosal routes of administration while analyzing the underpinning protective immune mechanisms; 2) validate this knowledge with response assays for monitoring vaccine efficacy and study safety aspects, including those associated with DNA vaccines; 3) approach implementation of prototype vaccines by optimizing vaccination strategies thus 4) shortening the route to exploitation. Thereby, this project will greatly enhance targeted disease prophylaxis in European fish farming.
Sait M.,Moredun Research Institute |
Sait M.,University of Melbourne |
Livingstone M.,Moredun Research Institute |
Clark E.M.,Moredun Research Institute |
And 8 more authors.
BMC Genomics | Year: 2014
Background: Chlamydia pecorum is the causative agent of a number of acute diseases, but most often causes persistent, subclinical infection in ruminants, swine and birds. In this study, the genome sequences of three C. pecorum strains isolated from the faeces of a sheep with inapparent enteric infection (strain W73), from the synovial fluid of a sheep with polyarthritis (strain P787) and from a cervical swab taken from a cow with metritis (strain PV3056/3) were determined using Illumina/Solexa and Roche 454 genome sequencing.Results: Gene order and synteny was almost identical between C. pecorum strains and C. psittaci. Differences between C. pecorum and other chlamydiae occurred at a number of loci, including the plasticity zone, which contained a MAC/perforin domain protein, two copies of a >3400 amino acid putative cytotoxin gene and four (PV3056/3) or five (P787 and W73) genes encoding phospholipase D. Chlamydia pecorum contains an almost intact tryptophan biosynthesis operon encoding trpABCDFR and has the ability to sequester kynurenine from its host, however it lacks the genes folA, folKP and folB required for folate metabolism found in other chlamydiae. A total of 15 polymorphic membrane proteins were identified, belonging to six pmp families. Strains possess an intact type III secretion system composed of 18 structural genes and accessory proteins, however a number of putative inc effector proteins widely distributed in chlamydiae are absent from C. pecorum. Two genes encoding the hypothetical protein ORF663 and IncA contain variable numbers of repeat sequences that could be associated with persistence of infection.Conclusions: Genome sequencing of three C. pecorum strains, originating from animals with different disease manifestations, has identified differences in ORF663 and pseudogene content between strains and has identified genes and metabolic traits that may influence intracellular survival, pathogenicity and evasion of the host immune system. © 2014 Sait et al.; licensee BioMed Central Ltd.
Clark J.R.,BigDNA Ltd. |
Bartley K.,Moredun Research Institute |
Jepson C.D.,Moredun Research Institute |
Craik V.,BigDNA Ltd. |
March J.B.,BigDNA Ltd.
FEMS Immunology and Medical Microbiology | Year: 2011
A bacteriophage lambda DNA vaccine expressing the small surface antigen (HBsAg) of hepatitis B was compared with Engerix B, a commercially available vaccine based on the homologous recombinant protein (r-HBsAg). Rabbits (five per group) were vaccinated intramuscularly at weeks 0, 5 and 10. Antibody responses against r-HBsAg were measured by indirect enzyme-linked immunosorbent assay, by limiting dilutions and by subtyping. Specific lymphocyte proliferation in vitro was also measured. After one vaccination, three of the five phage-vaccinated rabbits showed a strong antibody response, whereas no r-HBsAg-vaccinated animals responded. Following two vaccinations, all phage-vaccinated animals responded and antibody levels remained high throughout the experiment (220 days total). By 2 weeks after the second vaccination, antibody responses were significantly higher (P<0.05) in the phage-vaccinated group in all tests. After three vaccinations, one out of five r-HBsAg-vaccinated rabbit still failed to respond. The recognized correlate of protection against hepatitis B infection is an antibody response against the HBsAg antigen. When combined with the fact that phage vaccines are potentially cheap to produce and stable at a range of temperatures, the results presented here suggest that further studies into the use of phage vaccination against hepatitis B are warranted. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
Big DNA Ltd. | Date: 2015-09-23
BIGDNA Ltd | Date: 2011-03-29
Vaccine preparations. Scientific research services; analysis of disease conditions, namely, DNA analysis; research and analysis in the field of medicine in the nature of research into cures, treatment and prevention of disease. Medical services; medical diagnosis and treatment services; medical consultation services relating to the prophylactic treatment, cure and prevention of disease and therapy.
Agency: GTR | Branch: Innovate UK | Program: | Phase: Smart - Proof of Market | Award Amount: 25.00K | Year: 2014
BigDNA is a vaccine development company, using bacteriophages to deliver DNA vaccines. Arising as an additional output from a previous TSB SMART Proof of Concept project, the Company has identified a novel non-vaccine peptide-based cancer therapy which it believes may have significant clinical and commercial potential. This novel peptide combination has the potential to greatly increase clinical efficacy over existing therapies, and may offer a fast track route through to regulatory approval. BigDNA wishes to perform a full analysis of the intellectual property position surrounding this novel therapeutic, as well as a full commercial assessment of the opportunities available to such a product. This will also cover a detailed competitor and licensee analysis. If a positive Proof of Market analysis is obtained, then full technical development of this novel product can begin.
Agency: GTR | Branch: Innovate UK | Program: | Phase: Smart - Proof of Concept | Award Amount: 95.00K | Year: 2013
Bacteriophage (phage) offer the potential to deliver both protein and DNA vaccines within the same construct. They also promise extremely rapid development and manufacturing timescales, since the DNA vaccine cassette can be synthesised to express antigens for virtually any pathogen, literally within days following sequence identification. Phage are extremely robust, and can be delivered orally or in combination with other vaccines, and being particulate antigens, are naturally targeted to antigen presenting cells. BigDNA holds patents surrounding bacteriophage-based DNA and DNA/protein (chimeric) vaccines. To date, our focus has been on using bacteriophage lambda. The company now wishes to explore the potential for using phage M13 as an alternative vehicle for this technology. M13 is extremely well characterised with an excellent manufacturing base, and offers enormous technological potential. Phage-based DNA vaccine technology has been developed and patented by BigDNA in the UK, and has already attracted overseas investment, commercial collaborative R & D activity, and a licensing agreement with big pharma. This project aims to investigate the potential of a range of modifications designed to optimise and develop M13 as a platform for this purpose which should result in a vaccine platform and products capable of addressing a wide range of infectious diseases and cancers for which current vaccines either do not exist, or alternatively, cannot be developed in the rapid timescales likely required for pandemic disease indications.
BigDNA Ltd | Date: 2015-10-06
Big DNA Ltd | Date: 2016-08-19
Pharmaceuticals; vaccines for humans; diagnostic preparations for medical or clinical use; diagnostic reagents for medical or clinical use. Providing medical and scientific research information in the field of pharmaceuticals and clinical trials; design and development of pharmaceutical products; pharmaceutical research; clinical research; medical research; pharmaceutical research and design services; scientific laboratory services; research in the field of clinical trials; information and consultancy relating to the aforesaid. Medical analysis services.