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Eberhard R.,University of Zürich | Stergiou L.,University of Zürich | Stergiou L.,Redbiotec | Hofmann E.R.,University of Zürich | And 8 more authors.
PLoS Genetics | Year: 2013

Synthesis of ribosomal RNA by RNA polymerase I (RNA pol I) is an elemental biological process and is key for cellular homeostasis. In a forward genetic screen in C. elegans designed to identify DNA damage-response factors, we isolated a point mutation of RNA pol I, rpoa-2(op259), that leads to altered rRNA synthesis and a concomitant resistance to ionizing radiation (IR)-induced germ cell apoptosis. This weak apoptotic IR response could be phenocopied when interfering with other factors of ribosome synthesis. Surprisingly, despite their resistance to DNA damage, rpoa-2(op259) mutants present a normal CEP-1/p53 response to IR and increased basal CEP-1 activity under normal growth conditions. In parallel, rpoa-2(op259) leads to reduced Ras/MAPK pathway activity, which is required for germ cell progression and physiological germ cell death. Ras/MAPK gain-of-function conditions could rescue the IR response defect in rpoa-2(op259), pointing to a function for Ras/MAPK in modulating DNA damage-induced apoptosis downstream of CEP-1. Our data demonstrate that a single point mutation in an RNA pol I subunit can interfere with multiple key signalling pathways. Ribosome synthesis and growth-factor signalling are perturbed in many cancer cells; such an interplay between basic cellular processes and signalling might be critical for how tumours evolve or respond to treatment. © 2013 Eberhard et al.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.3.0-1 | Award Amount: 6.09M | Year: 2013

As current influenza vaccines only afford limited protection against seasonal as well as pandemic influenza, and require regular updating, the development of a universal influenza vaccine that can provide broad coverage against different strains within a subtype or even across subtypes has become a key health care priority in both industrialized and low and middle income countries. EDUFLUVAC aims to develop an influenza vaccine that educates the immune system to recognise common influenza epitopes, using a combination of influenza haemagglutinin (HA) antigens delivered on a single virus-like particle. This vaccine concept, using the proven, modern technology of baculovirus VLPs will enable enhanced cross linking of B-cell receptors and favour induction of B-cell responses against common epitopes essential for long-lasting cross recognition and protection. The mechanism underlying the broadening of antibody responses is the increased relative concentration of common epitopes diluting out strain specific epitopes. This will be achieved by testing the ability of a combination of historic HA variants to protect against a variety of modern isolates. A similar approach for developing a novel vaccine for pandemic use will be tested. The knowledge generated will provide Proof of Principle in relevant animal models for an influenza vaccine that does not have to be updated annually, does not have to be manufactured on an annual basis and will not require an annual vaccination campaign. It will also provide for an economically viable large scale production platform for influenza vaccine which, in the event of a pandemic, can manufacture rapidly high quantities of vaccine. All industrial partners (including two SMEs) will benefit from the compilation of the regulatory dossier for transfer to larger vaccine companies and the deeper knowledge integration emanating from EDUFLUVAC in a $2.8 billion global annual influenza vaccine market.


Sendoel A.,University of Zürich | Sendoel A.,Rockefeller University | Sendoel A.,Redbiotec | Maida S.,German Center for Neurodegenerative Diseases | And 14 more authors.
Nature Cell Biology | Year: 2014

Microtubule-targeting chemotherapeutics induce apoptosis in cancer cells by promoting the phosphorylation and degradation of the anti-apoptotic BCL-2 family member MCL1. The signalling cascade linking microtubule disruption to MCL1 degradation remains however to be defined. Here, we establish an in vivo screening strategy in Caenorhabditis elegans to uncover genes involved in chemotherapy-induced apoptosis. Using an RNAi-based screen, we identify three genes required for vincristine-induced apoptosis. We show that the DEP domain protein LET-99 acts upstream of the heterotrimeric G protein alpha subunit GPA-11 to control activation of the stress kinase JNK-1. The human homologue of LET-99, DEPDC1, similarly regulates vincristine-induced cell death by promoting JNK-dependent degradation of the BCL-2 family protein MCL1. Collectively, these data uncover an evolutionarily conserved mediator of anti-tubulin drug-induced apoptosis and suggest that DEPDC1 levels could be an additional determinant for therapy response upstream of MCL1. © 2014 Macmillan Publishers Limited. All rights reserved.


Ries C.,ZHAW Zurich University of Applied Sciences | John G.,PreSens Precision Sensing GmbH | John C.,Redbiotec | Eibl R.,ZHAW Zurich University of Applied Sciences | Eibl D.,ZHAW Zurich University of Applied Sciences
Engineering in Life Sciences | Year: 2010

While wave-mixed and stirred bag bioreactors are common devices for rapid, safe insect cell culture-based production at liter-scale, orbitally shaken disposable flasks are mainly used for screening studies at milliliter-scale. In contrast to the two aforementioned bag bioreactor types, which can be operated with standard or disposable sensors, shaker flasks have not been instrumented until recently. The combination of 250mL disposable shake flasks with PreSens's Shake Flask Reader enables both pH and dissolved oxygen to be measured, as well as allowing characterization of oxygen mass transfer. Volumetric oxygen transfer coefficients (k La-values) for PreSens 250mL disposable shake flasks, which were determined for the first time in insect cell culture medium at varying culture volumes and shaker frequencies, ranged between 4.4 and 37.9/h. Moreover, it was demonstrated that online monitoring of dissolved oxygen in shake flasks is relevant for limitation-free growth of insect cells up to high cell densities in batch mode (1.6×10 7 cells/mL) and for the efficient expression of an intracellular model protein. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.


Bredl S.,Redbiotec | Bredl S.,University of Regensburg | Plentz A.,University of Regensburg | Wenzel J.J.,University of Regensburg | And 3 more authors.
Journal of Clinical Virology | Year: 2011

Background: Acute parvovirus B19 (B19V) infection is characterized by high-level viremia. Antibodies against the capsid proteins VP1 and VP2 may complex with B19V-particles thereby becoming undetectable in diagnostic tests. Objectives: We intended to obtain data on the frequency of false-negative serology in acute B19V-infection. Study design: 129 plasma or serum samples of healthy blood donors and of patients with suspected B19V-infection were analyzed for B19V-DNA by qPCR and VP1/VP2-specific IgG and IgM by ELISA. Eleven of these samples were derived from four pregnant women with previous contact to B19V-infected individuals. Using acidic conditions virus/antibody-complexes were disrupted and detected by WesternLine and ELISA. Results: 83/118 samples were derived from acutely infected individuals displaying viremia (10 3-10 12geq/mL). In 24/83 viremic samples (28.9%) VP1/VP2-specific IgM and IgG were undetectable in ELISA, but could be demonstrated to be complexed with B19V-particles. Each 7/83 (8.4%) was IgM-positive/IgG-negative and IgM-negative/IgG-positive, in 45/83 samples (54.2%) IgG and IgM could be detected. 35 samples did not contain B19V-DNA; five of these were from seronegative persons. Analyzing consecutive sera derived from four pregnant women, B19V-DNA was demonstrated in 10/11 samples, B19V-specific IgG- and IgM-antibodies were detectable in 10/11 and 4/11 samples, respectively. In 2/4 women seroconversion was observed, but IgM was not detected in 50% of the samples. B19V-specific IgG but not IgM was detectable in 2/4 women. Conclusion: Acute B19V-infection cannot be diagnosed by exclusive analysis of B19V-specific antibodies. Only the combination of assays for detection of B19V-DNA and antibodies enables correct serodiagnosis. © 2011 Elsevier B.V.


The invention describes novel virus-like particles for use as vaccines, diagnostic tools and R&D tools based on recombinant DNA and cell cultivation techniques for production. The recombinant virus-like particles of the invention are assembled by polypeptide chains that incorporate several, in particular two or more, different epitopes which are selected either (a) from different viral strains of the same virus and/or (b) from different serotypes of the same virus and/or (c) from different viral strains specific for different hosts. These epitopes are then displayed on the particle surface.


The invention describes novel virus-like particles for use as vaccines, diagnostic tools and R&D tools based on recombinant DNA and cell cultivation techniques for production. The recombinant virus-like particles of the invention are assembled by polypeptide chains that incorporate several, in particular two or more, different epitopes which are selected either (a) from different viral strains of the same virus and/or (b) from different serotypes of the same virus and/or (c) from different viral strains specific for different hosts. These epitopes are then displayed on the particle surface.


News Article | January 5, 2015
Site: www.businesswire.com

NEW YORK--(BUSINESS WIRE)--Pfizer Inc. today announced that it has acquired a controlling interest in Redvax GmbH, a spin-off from Redbiotec AG, a privately held Swiss biopharmaceutical company, based in Zurich-Schlieren. This transaction provides access to a preclinical human cytomegalovirus (CMV) vaccine candidate, as well as intellectual property and a technology platform related to a second, undisclosed vaccine program. The CMV vaccine program will complement Pfizer’s robust research portfolio of high-quality and life-saving investigational vaccines and place Pfizer among the leaders in CMV research and development. CMV is a herpes virus, infecting 50-90% of the adult population, with a majority remaining asymptomatic. A large segment of young adults, especially women of childbearing age who remain CMV negative, are at high risk of CMV infection during pregnancy and of passing the infection on to the unborn child (congenital infection). 1,2 There are potentially serious and lifelong consequences for babies born with the disease. One out of every five children born with CMV infection may experience hearing loss and severe neurologic disorders.3 More children have disabilities due to congenital CMV than other well-known infections and syndromes, including Down syndrome, fetal alcohol syndrome, spina bifida, and pediatric HIV/AIDS.4 “We are working to bring innovative vaccines to market that prevent and treat serious diseases,” said Kathrin U. Jansen, Ph.D., senior vice president & CSO Vaccine Research & Early Development for Pfizer. “Through the acquisition of the Redvax innovative CMV vaccine platform and expertise we will seek to develop a vaccine to prevent a difficult disease that can have a devastating and lifelong impact on young children.” The U.S. Centers for Disease Control and Prevention (CDC) estimate that, in the U.S., approximately 5,000 children each year develop lasting health problems caused by CMV such as hearing or vision loss, and mental disability.5 The Institute of Medicine (IOM) has ranked the development of a CMV vaccine as a highest priority because of the lives it would save and the disabilities it would prevent.5 The estimated costs associated with CMV disease for the U.S. health care system amounts to at least $1.86 billion annually. CMV expenses can run more than $300,000 per child.6 Christian Schaub, CEO of Redbiotec and Managing Director of Redvax commented, “We are pleased to have completed this deal with Pfizer, a global leader in vaccines. This represents an important step toward the development of a much needed vaccine for CMV, a disease that has a devastating impact on children and families. We believe that combining Redvax’s assets with Pfizer’s commitment, expertise and resources will significantly enhance the potential of developing this important vaccine.” About Pfizer Inc. At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world's best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, Pfizer has worked to make a difference for all who rely on us. To learn more, please visit us at www.pfizer.com. About Redvax GmbH Redvax is a spin-off from Redbiotec AG, a privately held Swiss biopharmaceutical company, based in Zurich-Schlieren. Redvax is a preclinical stage company. The company develops multi-component virus-like particles (VLPs) and other protein assemblies for vaccine development in the field of CMV and a further undisclosed field. DISCLOSURE NOTICE The information contained in this release is as of January 5, 2015. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. This release contains forward-looking information about a preclinical CMV vaccine candidate and the acquisition by Pfizer of a controlling interest in Redvax GmbH, including the potential benefits thereof, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including the ability to meet anticipated pre-clinical and clinical study commencement and completion dates as well as the possibility of unfavorable study results; whether and when biologics license applications may be filed in any jurisdictions for the CMV vaccine candidate; whether and when any such applications may be approved by regulatory authorities, which will depend on the assessment by such regulatory authorities of the benefit-risk profile suggested by the totality of the efficacy and safety information submitted; decisions by regulatory authorities regarding labeling and other matters that could affect the availability or commercial potential of the CMV vaccine candidate; the ability to realize the anticipated benefits of the acquisition; other business effects, including the effects of industry, economic, political or regulatory conditions; and competitive developments. A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2013, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information That May Affect Future Results”, as well as in its subsequent reports on Form 10-Q and Form 8-K, all of which are filed with the SEC and available at www.sec.gov and www.pfizer.com. 3 Manicklal, S. et. al., The “Silent” Global Burden of Congenital Cytomegalovirus, Clin. Microbiol. Rev. January 2013 4 Cannon, MJ. et. al., Washing our Hands of the Congenital Cytomegalovirus Disease Epidemic, BMC Public Health., 6 Arvin, A. et. al., Vaccine Development to Prevent Cytomegalovirus Disease: Report from the National Vaccine Advisory Committee, Clinical Infectious Diseases 2004; 39:233–9


News Article | January 5, 2015
Site: www.fiercebiotech.com

Pfizer ($PFE) has added an acquisition pact to its latest string of deals. The pharma giant said today that it is buying out Redvax, a subsidiary of Switzerland's Redbiotec, in order to get its hands on a preclinical cytomegalovirus (CMV) vaccine candidate. There were no numbers in the announcement, but Pfizer says it gained a controlling interest in the vaccine subsidiary, gaining bragging rights as one of the leaders in CMV research. CMV is a herpes virus, infecting 50% to 90% of the adult population, though most people remain asymptomatic. But a vaccine could prove useful in preventing pregnant women from passing the virus along to their unborn children. Vaccines represent one of Pfizer's 6 core R&D focuses. Its pipeline already includes new jabs designed to prevent infections like Meningococcal B, hospital-acquired Staphylococcus aureus infection and Clostridium difficile colitis. Therapeutic vaccines for smoking cessation and allergic asthma are also in development. Pfizer was stymied for much of 2014 by its unsuccessful bid to buy AstraZeneca ($AZN). But in the last few weeks the deal team at the pharma giant has been unleashed. Just two weeks ago Pfizer partnered with Opko Health on a Phase III long acting growth hormone, paying $295 million upfront and promising up to $275 million more on regulatory milestones. That deal closely followed a gene therapy partnership with Spark Therapeutics, which came just weeks after Pfizer made an $850 million upfront payment to partner with Merck KGaA on a preclinical immuno-oncology program, marking the highest upfront ever paid in an industry licensing deal. Back in July, Zurich-based Redbiotec teamed with GE Healthcare Life Sciences ($GE) to produce new CMV vaccine candidates. "We are working to bring innovative vaccines to market that prevent and treat serious diseases," said Kathrin U. Jansen, Ph.D., senior vice president & CSO Vaccine Research & Early Development for Pfizer. "Through the acquisition of the Redvax innovative CMV vaccine platform and expertise we will seek to develop a vaccine to prevent a difficult disease that can have a devastating and lifelong impact on young children." Related Articles: Pfizer continues spending spree with $295M upfront for PhIII growth hormone Pfizer strikes another immunotherapy deal to widen its oncology pipeline Pfizer buys into gene therapy's renaissance and bets on Spark Therapeutics

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