Forbes E.K.,University of Oxford |
de Cassan S.C.,University of Oxford |
Llewellyn D.,University of Oxford |
Biswas S.,University of Oxford |
And 6 more authors.
PLoS ONE | Year: 2012
Viral vectored vaccines have been shown to induce both T cell and antibody responses in animals and humans. However, the induction of even higher level T cell responses may be crucial in achieving vaccine efficacy against difficult disease targets, especially in humans. Here we investigate the oligomerization domain of the α-chain of C4b-binding protein (C4 bp) as a candidate T cell "molecular adjuvant" when fused to malaria antigens expressed by human adenovirus serotype 5 (AdHu5) vectored vaccines in BALB/c mice. We demonstrate that i) C-terminal fusion of an oligomerization domain can enhance the quantity of antigen-specific CD4+ and CD8+ T cell responses induced in mice after only a single immunization of recombinant AdHu5, and that the T cells maintain similar functional cytokine profiles; ii) an adjuvant effect is observed for AdHu5 vectors expressing either the 42 kDa C-terminal domain of Plasmodium yoelii merozoite surface protein 1 (PyMSP142) or the 83 kDa ectodomain of P. falciparum strain 3D7 apical membrane antigen 1 (PfAMA1), but not a candidate 128kDa P. falciparum MSP1 biallelic fusion antigen; iii) following two homologous immunizations of AdHu5 vaccines, antigen-specific T cell responses are further enhanced, however, in both BALB/c mice and New Zealand White rabbits no enhancement of functional antibody responses is observed; and iv) that the T cell adjuvant activity of C4 bp is not dependent on a functional Fc-receptor γ-chain in the host, but is associated with the oligomerization of small (<80 kDa) antigens expressed by recombinant AdHu5. The oligomerization domain of C4 bp can thus adjuvant T cell responses induced by AdHu5 vectors against selected antigens and its clinical utility as well as mechanism of action warrant further investigation.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-06-2016 | Award Amount: 23.70M | Year: 2017
A highly effective malaria vaccine against Plasmodium falciparum should help prevent half a million deaths from malaria each year. New vaccine technologies and antigen discovery approaches now make accelerated design and development of a highly effective multi-antigen multi-stage subunit vaccine feasible. Leading malariologists, vaccine researchers and product developers will here collaborate in an exciting programme of antigen discovery science linked to rapid clinical development of new vaccine candidates. Our approach tackles the toughest problems in malaria vaccine design: choice of the best antigens, attaining high immunogenicity, avoiding polymorphic antigens and increasing the durability of vaccine immunogenicity and efficacy. We take advantage of several recent advances in vaccinology and adopt some very new technologies: sequencing malaria peptides eluted from the HLA molecules, parasites expressing multiple transgenes, multi-antigen virus-like particles constructed with new bonding technologies, delayed release microcapsules, and liver-targeted immunisation with vaccine vectors. We enhance our chances of success by using a multi-stage multi-antigen approach, by optimising the magnitude and durability of well-characterised immune responses to key antigens, and using stringent infectious challenges and functional assays as established criteria for progression at each stage. The consortium comprises many of the foremost researchers in this field in Europe with leading groups in the USA, Australia and Africa. We link to EDCTP programmes and harmonise our timeline to fit with the recent roadmaps for malaria vaccine development. We include a major pharma partner and several excellent European biotech companies helping enhance Europes leading position in the commercial development of vaccines. This ambitious and exciting programme should have a high chance of success in tackling the major global health problem posed by malaria.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-06-2016 | Award Amount: 5.76M | Year: 2017
Plasmodium vivax is the most widespread malaria and constitutes a significant proportion of human malaria cases. P. vivax accounts for 100-400 million clinical cases each year among the 2.5 billion people living at risk in Latin America, Oceania and Asia. The recently revised Malaria Vaccine Technology Roadmap to 2030 recognises the severity of P. vivax malaria and calls for a vaccine intervention to achieve 75% efficacy over two years equally weighted with P. falciparum. However, despite this global health need, efforts to develop interventions against this parasite have lagged far behind those for P. falciparum, in large part because of critical bottlenecks in the vaccine development process. These include i) lack of assays to prioritise and down-select new vaccines due to lack of an in vitro P. vivax long-term culture system, and ii) lack of easy access to a safe controlled human malaria infection (CHMI) model to provide an early indication of vaccine efficacy in humans. The Objectives of this MultiViVax proposal will address these critical bottlenecks and shift the risk curve in order to better select successful vaccine candidates against multiple lifecycle stages of P. vivax: 1. We will establish a P. vivax CHMI model in Europe for the first time to facilitate the better selection of effective vaccines and remove the current bottleneck for their early-phase clinical testing. 2. We will utilise this CHMI model to identify novel antigens associated with protective blood-stage immunity in humans by taking advantage of recent advances in immuno-screening and parasite RNASeq. 3. We will progress existing vaccines targeting the current leading antigens for both the blood- and transmission-stages along the clinical development pipeline. 4. We will develop novel transgenic parasites for use in assays in order to overcome the current bottleneck in vaccine down-selection caused by the inability to culture P. vivax parasites.
Imaxio Sa and ISIS INNOVATION Ltd | Date: 2010-10-15
There is provided a fusion protein or a polynucleotide sequence encoding said fusion protein that comprises first and second domains, wherein the first domain of the fusion protein comprises an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 1, or a fragment thereof comprising at least 20 consecutive amino acids thereof; and wherein the second domain of the fusion protein comprises a mycobacterial antigen or an antigenic fragment thereof. Also provided are corresponding therapeutic uses thereof for the protection of primates against mycobacterial infections.
News Article | November 21, 2016
ReportsnReports.com adds "Tuberculosis - Pipeline Review, H2 2016" to its store providing comprehensive information on the therapeutics under development for Tuberculosis (Respiratory), complete with analysis by stage of development, drug target, mechanism of action (MoA), route of administration (RoA) and molecule type. The guide covers the descriptive pharmacological action of the therapeutics, its complete research and development history and latest news and press releases. Complete report on H2 2016 pipeline review of Tuberculosis with 108 market data tables and 17 figures, spread across 393 pages is available at http://www.reportsnreports.com/reports/755901-tuberculosis-pipeline-review-h2-2016.html. Tuberculosis, commonly known as TB, is a bacterial infection that can spread through the lymph nodes and bloodstream to any organ in body. It is most often found in the lungs. The symptoms of tuberculosis range from no symptoms (latent tuberculosis) to symptoms of active disease. Symptoms include overall sensation of feeling unwell; cough, possibly with bloody mucus, fatigue, shortness of breath, weight loss and pain in the chest. Companies discussed in this Tuberculosis Pipeline Review, H2 2016 report include Abera Bioscience AB, Akthelia Pharmaceuticals Limited, Alvogen Korea Co., Ltd., Anacor Pharmaceuticals, Inc., Archivel Farma S.L., AstraZeneca Plc, Beech Tree Labs, Inc., BioDiem Ltd, BioLingus AG, Biomar Microbial Technologies, Bioversys AG, Celgene Corporation, Cellceutix Corporation, Chongqing Zhifei Biological Products Co., Ltd., Crestone, Inc., Dafra Pharma International Ltd., Daiichi Sankyo Company, Limited, Demuris Limited, Eisai Co., Ltd., Eli Lilly and Company, Ensol Biosciences Inc., EpiVax, Inc., FIT Biotech Oy, GangaGen Inc., GlaxoSmithKline Plc, Globeimmune, Inc., Hager Biosciences, LLC, Hsiri Therapeutics LLC, Imaxio SA, Immunitor, Inc., ImmunoBiology Limited, Inovio Pharmaceuticals, Inc., Johnson & Johnson, Lakewood-Amedex Inc, Lipotek Pty Ltd., Matinas BioPharma Holdings, Inc., Microbion Corporation, Microbiotix, Inc., NEARMEDIC PLUS, Ltd, Novartis AG, NovoBiotic Pharmaceuticals, LLC, Otsuka Holdings Co., Ltd., QureTech Bio AB, Recce Pty Ltd, Rodos BioTarget GmbH, Sanofi, Sanofi Pasteur SA, Sarepta Therapeutics, Inc., Sequella, Inc., Shionogi & Co., Ltd., Sphaera Pharma Pvt. Ltd., Spring Bank Pharmaceuticals, Inc., Takeda Pharmaceutical Company Limited, TetraLogic Pharmaceuticals, TGV-Laboratories, Theravectys SA, Tomegavax, Inc., Transgene SA, TVAX Biomedical, Inc., Univalue Valorizacion, S.L., Vaccibody AS, Vakzine Projekt Management GmbH, Vaxil Bio Therapeutics Ltd. and Vichem Chemie Research Ltd. The Tuberculosis (Infectious Disease) pipeline guide also reviews of key players involved in therapeutic development for Tuberculosis and features dormant and discontinued projects. The guide covers therapeutics under Development by Companies /Universities /Institutes, the molecules developed by Companies in Pre-Registration, Phase III, Phase II, Phase I, Preclinical, Discovery and Unknown stages are 1, 5, 7, 8, 61, 37 and 3 respectively. Similarly, the Universities portfolio in Phase III, Phase II, Phase I, Preclinical and Discovery stages comprises 2, 4, 5, 35 and 37 molecules, respectively. Tuberculosis (Infectious Disease) pipeline guide helps in identifying and tracking emerging players in the market and their portfolios, enhances decision making capabilities and helps to create effective counter strategies to gain competitive advantage. The guide is built using data and information sourced from Global Markets Direct’s proprietary databases, company/university websites, clinical trial registries, conferences, SEC filings, investor presentations and featured press releases from company/university sites and industry-specific third party sources. Additionally, various dynamic tracking processes ensure that the most recent developments are captured on a real time basis. The report helps in identifying and tracking emerging players in the market and their portfolios, enhances decision making capabilities and helps to create effective counter strategies to gain competitive advantage. Scope of this report: The report provides a snapshot of the global therapeutic landscape of Tuberculosis and reviews pipeline therapeutics for Tuberculosis by companies and universities/research institutes based on information derived from company and industry-specific sources and key players involved Tuberculosis therapeutics and enlists all their major and minor projects. The research covers pipeline products based on various stages of development ranging from pre-registration till discovery and undisclosed stages. The report features descriptive drug profiles for the pipeline products which includes, product description, descriptive MoA, R&D brief, licensing and collaboration details & other developmental activities and assesses Tuberculosis therapeutics based on drug target, mechanism of action (MoA), route of administration (RoA) and molecule type. The report summarizes all the dormant and discontinued pipeline projects with latest news related to pipeline therapeutics for Tuberculosis. ReportsnReports.com is your single source for all market research needs. Our database includes 500,000+ market research reports from over 100+ leading global publishers & in-depth market research studies of over 5000 micro markets. With comprehensive information about the publishers and the industries for which they publish market research reports, we help you in your purchase decision by mapping your information needs with our huge collection of reports. Connect With Us on: Facebook: https://www.facebook.com/ReportsnReports/ LinkedIn: https://www.linkedin.com/company/reportsnreports Twitter: https://twitter.com/marketsreports G+ / Google Plus: https://plus.google.com/111656568937629536321/posts RSS/Feeds: http://www.reportsnreports.com/feed/l-latestreports.xml
Campbell T.A.,Texas A&M University-Kingsville |
Garcia M.R.,Texas A&M University-Kingsville |
Miller L.A.,National Wildlife Research Center |
Ramirez M.A.,Texas A&M University-Kingsville |
And 3 more authors.
Journal of Swine Health and Production | Year: 2010
Objective: To determine if a recombinant gonadotropin-releasing hormone (GnRH) vaccine is a potential immunocontraceptive agent for juvenile male feral swine. Materials and methods: At the beginning of the trial (Day 0) we treated animals in Treatment One with a single injection of a sham vaccine containing 1 mL of a buffer-adjuvant emulsion (adjuvant: AdjuVac; National Wildlife Research Center, Fort Collins, Colorado). Treatment Two received 1000 μg of a recombinant GnRH (rGnRH) vaccine (IMX294; Imaxio, Lyon, France). Treatment Three received 500 μg of a rGnRH vaccine. Treatment Four received 1000 μg of a GnRH vaccine (GonaCon; National Wildlife Research Center, Fort Collins, Colorado). On Day 90, Treatment Three received an additional 500-μg boost treatment. All vaccines were emulsified with AdjuVac and injected intramuscularly into the rump. On Day 180, we performed necropsies on swine and compared mass of testes, percent normal seminiferous tubules, numbers of spermatogonia, spermatocytes, and spermatids, serum testosterone levels, and anti-GnRH antibody titers among treatments. Results: As expected, a single dose of GonaCon vaccine reduced testes mass, serum testosterone, and percent normal tubules, and restricted sperm development at each stage. These reductions in reproductive development were associated with elevated GnRH antibodies. The single injection of rGnRH was not as effective in reducing these reproductive parameters; however, the two-dose injection of rGnRH was as effective as the single injection of GonaCon. Implication: Further research and development is needed into oral immunocontraceptive vaccines and oral delivery systems.
Spencer A.J.,University of Oxford |
Hill F.,Imaxio SA |
Honeycutt J.D.,University of Oxford |
Cottingham M.G.,University of Oxford |
And 9 more authors.
PLoS ONE | Year: 2012
To prevent important infectious diseases such as tuberculosis, malaria and HIV, vaccines inducing greater T cell responses are required. In this study, we investigated whether fusion of the M. tuberculosis antigen 85A to recently described adjuvant IMX313, a hybrid avian C4bp oligomerization domain, could increase T cell responses in pre-clinical vaccine model species. In mice, the fused antigen 85A showed consistent increases in CD4 + and CD8 + T cell responses after DNA and MVA vaccination. In rhesus macaques, higher IFN-γ responses were observed in animals vaccinated with MVA-Ag85A IMX313 after both primary and secondary immunizations. In both animal models, fusion to IMX313 induced a quantitative enhancement in the response without altering its quality: multifunctional cytokines were uniformly increased and differentiation into effector and memory T cell subsets was augmented rather than skewed. An extensive in vivo characterization suggests that IMX313 improves the initiation of immune responses as an increase in antigen 85A specific cells was observed as early as day 3 after vaccination. This report demonstrates that antigen multimerization using IMX313 is a simple and effective cross-species method to improve vaccine immunogenicity with potentially broad applicability. © 2012 Spencer et al.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.3.1-1 | Award Amount: 7.11M | Year: 2013
Staphylococcus aureus, including Meticillin-resistant S. aureus (MRSA), is one of the most important bacterial pathogens, causing skin, wound, and deep infections in both the community and in hospitals. Treatment is difficult and expensive and may require prolonged intravenous antibiotic therapy. Since there is no licensed vaccine by FDA or EMEA, prevention also relies heavily on antimicrobials to which antibiotic resistance is developing. To reduce S. aureus disease burden, and antibiotic use associated with it, BELLEROPHON will design, manufacture, and assess in a Phase I clinical study a novel S. aureus vaccine candidate targeting both the cellular and humoral responses. It is designed to be protective against both MRSA and more sensitive S. aureus strains. The project will rely on 4 key components: i) a recently discovered and highly conserved T-cell inducing antigen individually capable of eliciting substantial protection in mouse models; (ii) a secreted toxin antigen, antibodies against which reduce mortality (Hla); (iii) an innovative, proprietary and potent pro-immunogenic series of tags (IMX313 series) which can be fused to the antigens; (iv) the use of viral vectors, including an innovative and proprietary adenoviral vector (ChAdOx1) and/or new ways to use viral vectors to generate protective immunity (MVA mixed with proteins). We will i) identify the most protective method of combining these components in a manufacturable and clinically deployable manner; ii) manufacture and perform initial human studies of the vaccine; iii) identify additional antigens which might further increase the efficacy of the initial product. Our approach will contribute clinical safety and immunogenicity data for a novel vaccine strategy targeting one of the key bacterial pathogens in man. It will pave the way for rapid progression to phase II studies, and thence to larger phase II/III studies aiming to reduce infection.
Allen E.R.,University of Oxford |
Van Diemen P.,University of Oxford |
Yamaguchi Y.,University of Oxford |
Lindemann C.,University of Oxford |
And 5 more authors.
PLoS ONE | Year: 2016
Purpose: To develop and validate a sensitive and specific method of abscess enumeration and quantification in a preclinical model of Staphylococcus aureus infection. Methods: S. aureus infected murine kidneys were fixed in paraformaldehyde, impregnated with gadolinium, and embedded in agar blocks, which were subjected to 3D magnetic resonance microscopy on a 9.4T MRI scanner. Image analysis techniques were developed, which could identify and quantify abscesses. The result of this imaging was compared with histological examination. The impact of a S. aureus Sortase A vaccination regime was assessed using the technique. Results: Up to 32 murine kidneys could be imaged in a single MRI run, yielding images with voxels of about 25 μm3. S. aureus abscesses could be readily identified in blinded analyses of the kidneys after 3 days of infection, with low inter-observer variability. Comparison with histological sections shows a striking correlation between the two techniques: all presumptive abscesses identified by MRI were confirmed histologically, and histology identified no abscesses not evident on MRI. In view of this, simulations were performed assuming that both MRI reconstruction, and histology examining all sections of the tissue, were fully sensitive and specific at abscess detection. This simulation showed that MRI provided more sensitive and precise estimates of abscess numbers and volume than histology, unless at least 5 histological sections are taken through the long axis of the kidney. We used the MRI technique described to investigate the impact of a S. aureus Sortase A vaccine. Conclusion: Post mortem MRI scanning of large batches of fixed organs has application in the preclinical assessment of S. aureus vaccines. © 2016 Allen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.