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Xing Y.,Glaxosmithkline | Oliver S.L.,Stanford University | Nguyen T.,Glaxosmithkline | Ciferri C.,Glaxosmithkline | And 12 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

Varicella-zoster virus (VZV), of the family Alphaherpesvirinae, causes varicella in children and young adults, potentially leading to herpes zoster later in life on reactivation from latency. The conserved herpesvirus glycoprotein gB and the heterodimer gHgL mediate virion envelope fusion with cell membranes during virus entry. Naturally occurring neutralizing antibodies against herpesviruses target these entry proteins. To determine the molecular basis for VZV neutralization, crystal structures of gHgL were determined in complex with fragments of antigen binding (Fabs) from two human monoclonal antibodies, IgG-94 and IgG-RC, isolated from seropositive subjects. These structures reveal that the antibodies target the same site, composed of residues from both gH and gL, distinct from two other neutralizing epitopes identified by negative-stain electron microscopy and mutational analysis. Inhibition of gB/gHgL-mediated membrane fusion and structural comparisons with herpesvirus homologs suggest that the IgG-RC/94 epitope is in proximity to the site on VZV gHgL that activates gB. Immunization studies proved that the anti-gHgL IgG-RC/94 epitope is a critical target for antibodies that neutralize VZV. Thus, the gHgL/Fab structures delineate a site of herpesvirus vulnerability targeted by natural immunity.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2011.1.4-4 | Award Amount: 40.88M | Year: 2011

Vaccines so far have been developed mostly by following an empiric approach. To prevent and possibly cure unresolved and emerging infectious diseases we need to fully exploit the potential of the human immune system. Progress in science and technology makes it possible to achieve what was previously deemed impossible. The scope of this project is to produce knowledge necessary to develop novel and powerful immunization technologies for the next generation of human vaccines. This goal requires a multidisciplinary approach in which diverse but complementary scientific disciplines and technologies converge. Therefore some of the most competitive European research groups from public institutions and biotechs have agreed to join forces in ADITEC, together with top US groups on systems biology and adjuvants to support this enterprise. A systems biology approach will be used to study licensed and experimental vaccines in patient characterization studies and in clinical trials, to investigate the effect of adjuvants, vectors, formulations, delivery devices, routes of immunization, homologous and heterologous primeboost schedules, as well as the impact of host factors such as age, gender, genetics and pathologies. Animal models will be used to complement human studies, and to select novel immunization technologies to be advanced to the clinic. To address these issues in a coordinated manner, ADITEC is organised on a matrix structure in which research themes and experimental approaches feed into each other. Training curricula will be created to impact on the formation of the next generation of EU researchers in the field. ADITEC scientists and institutions are part of the Sclavo Vaccines Association (SVA), which is dedicated to vaccines and vaccine research. SVA, acting as the coordinating institution, guarantees the long-term commitment and sustainability of this initiative, beyond the duration of ADITEC itself.


News Article | November 28, 2016
Site: www.newsmaker.com.au

The report provides comprehensive information on the therapeutics under development for Cytomegalovirus (HHV-5) Infections, complete with analysis by stage of development, drug target, mechanism of action (MoA), route of administration (RoA) and molecule type. The report also covers the descriptive pharmacological action of the therapeutics, its complete research and development history and latest news and press releases. Additionally, the report provides an overview of key players involved in therapeutic development for Cytomegalovirus (HHV-5) Infections   and features dormant and discontinued projects. 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. Complete report on Cytomegalovirus (HHV-5) Infections - Pipeline Review, H2 2016 addition with 53 market data tables and 16 figures, spread across 177 pages is available at http://www.reportsnreports.com/reports/764557-cytomegalovirus-hhv-5-infections-pipeline-review-h2-2016.html This report features investigational drugs from across globe covering over 20 therapy areas and nearly 3,000 indications. The report is built using data and information sourced from Global Markets Directs 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. Drug profiles featured in the report undergoes periodic review following a stringent set of processes to ensure that all the profiles are updated with the latest set of information. Additionally, various dynamic tracking processes ensure that the most recent developments are captured on a real time basis Adicet Bio, Inc.,AIMM Therapeutics BV,Astellas Pharma Inc,Atara Biotherapeutics Inc,AvidBiotics Corp,Biotest AG ,Chimerix Inc ,China Biologic Products Inc,CyTuVax BV ,Fate Therapeutics Inc,GlaxoSmithKline Plc,Hookipa Biotech AG,Kadmon Corp LLC,Laboratoires Thea SA,Merck & Co Inc ,Microbiotix Inc ,Mymetics Corp ,Novartis AG ,Pfizer Inc ,Phoenix Biotechnology Inc,Savoy Pharmaceuticals, Inc.,Sigma-Tau SpA ,Themis Bioscience GmbH Inquire before buying http://www.reportsnreports.com/contacts/inquirybeforebuy.aspx?name=764557premium report price at US$2000 for a single user PDF license).


Monath T.P.,Kleiner Perkins Caufield & Byers | Monath T.P.,Paxvax, Inc. | Monath T.P.,Hookipa Biotech | Seligman S.J.,New York Medical College | And 9 more authors.
Vaccine | Year: 2015

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus, Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were exchanged for the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of information. The Brighton Collaboration V3SWG template may also be useful as a guide to the evaluation of other recombinant viral vector vaccines. © 2014.


News Article | December 14, 2016
Site: www.marketwired.com

ATLANTA, GA--(Marketwired - Dec 14, 2016) -  GeoVax Labs, Inc. ( : GOVX), a biotechnology company specializing in developing human vaccines, announced today that Farshad Guirakhoo, PhD, has been promoted to the role of Chief Scientific Officer, effective January 1, 2017. Dr. Guirakhoo joined GeoVax in 2015 as Senior Vice President of Research and Development. Robert T. McNally, PhD, GeoVax's President and Chief Executive Officer, commented, "For the past year, Farshad has been a driving force behind the growth of our vaccine development pipeline, and we are pleased to expand his role at this critical time for our company. In the role of Chief Scientific Officer, Dr. Guirakhoo will lead the scientific advancement of GeoVax's technology pipeline as the Company identifies and pursues new opportunities to address significant medical needs." Dr. McNally continued, "Harriet Robinson, PhD, will continue to hold an instrumental position with GeoVax as Chief Scientific Officer Emeritus. In this role, she will continue to direct our HIV vaccine program as well as continuing to serve as principal investigator on grants to GeoVax from the National Institutes of Health. Dr. Robinson, a co-founder of GeoVax, will also continue to serve as a member of our Board of Directors." Before joining GeoVax in 2015, Dr. Guirakhoo served in senior management and scientific roles within the biotechnology industry with Vaxess Technologies, Hookipa Biotech, Sanofi Pasteur, Acambis, Inc. and OraVax, Inc. He earned his Ph.D. in Virology at the Medical University of Vienna, Vienna, Austria, holds a M.Sc. degree in Genetics and a B.Sc. degree in Biology. He conducted his Post-Doctoral training at the Medical University of Vienna and at the US National Centers for Disease Control and Prevention (CDC), Division of Vector-Borne Infectious Diseases in Fort Collins, CO. In his scientific career, Dr. Guirakhoo has filed over 90 patent applications and is author/co-author of more than 80 peer reviewed publications, including book chapters. He was instrumental in the development and commercialization of the Imojev Japanese encephalitis virus vaccine and the Dengvaxia vaccine for Dengue virus. In 2014, he was named as one of the 50 Most Influential People in Vaccines. About GeoVax GeoVax Labs, Inc., is a clinical-stage biotechnology company developing human vaccines against infectious diseases using its Modified Vaccinia Ankara-Virus Like Particle (MVA-VLP) vaccine platform. The Company's development programs are focused on vaccines against HIV, Zika, and hemorrhagic fever viruses (Ebola, Sudan, Marburg, and Lassa). GeoVax recently began programs to evaluate the use of its MVA-VLP platform in cancer immunotherapy and for therapeutic use in chronic Hepatitis B infections. GeoVax's vaccine platform supports in vivo production of non-infectious VLPs from the cells of the very person receiving the vaccine, mimicking a natural infection, stimulating both the humoral and cellular arms of the immune system to recognize, prevent, and control the target infection. For more information, visit www.geovax.com.


Monath T.P.,Hookipa Biotech | Monath T.P.,Paxvax, Inc. | Vasconcelos P.F.C.,Instituto Evandro Chagas | Vasconcelos P.F.C.,National Institute of Science and Technology for Viral Hemorrhagic Fevers | Vasconcelos P.F.C.,Pará State University
Journal of Clinical Virology | Year: 2015

Yellow fever, a mosquito-borne flavivirus disease occurs in tropical areas of South America and Africa. It is a disease of major historical importance, but remains a threat to travelers to and residents of endemic areas despite the availability of an effective vaccine for nearly 70 years. An important aspect is the receptivity of many non-endemic areas to introduction and spread of yellow fever. This paper reviews the clinical aspects, pathogenesis, and epidemiology of yellow fever, with an emphasis on recent changes in the distribution and incidence of the disease. Recent knowledge about yellow fever 17D vaccine mechanism of action and safety are discussed. © 2014 Elsevier B.V.


Wen Y.,Novartis | Monroe J.,Novartis | Linton C.,Novartis | Archer J.,Novartis | And 8 more authors.
Vaccine | Year: 2014

Human cytomegalovirus (HCMV) is a member of the β-herpesvirus family that causes significant disease worldwide. Although evidence exists that neutralizing antibodies and cytotoxic T cell responses to HCMV antigens can prevent HCMV disease and/or infection, there are no approved vaccines to prevent HCMV disease. Over the past 10 years, multiple HCMV vaccines have been tested in man but only partial protection has been achieved in these studies. HCMV contains multiple surface-expressed glycoproteins that are critical to viral entry, including gB, the gM/gN complex, the gH/gL complex, and a pentameric gH/gL/UL128/UL130/UL131A complex. Recently we showed that viral replicon particles (VRPs) expressing the gH/gL complex elicited more potently neutralizing antibodies than VRPs expressing gB in mice. Here we compare the immunogenicity of VRPs encoding the HCMV gH/gL and pentameric complexes, as well as purified gH/gL and pentameric complexes administered in the presence or absence of the MF59 adjuvant. The results of these studies indicate that the pentameric complex elicits significantly higher levels of neutralizing antibodies than the gH/gL complex, and that MF59 significantly increases the potency of each complex. In addition, we show that animals immunized with pentamer encoding VRPs or the pentameric subunit produce antibodies that recognize a broad range of antigenic sites on the complex. Taken together, these studies support the utility of the pentameric complex in HCMV vaccine candidates. © 2014 Elsevier Ltd.

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