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News Article | May 18, 2017
Site: www.eurekalert.org

May 18, 2017 -- (BRONX, NY) -- After analyzing the blood of a survivor of the 2013-16 Ebola outbreak, a team of scientists from academia, industry and the government has discovered the first natural human antibodies that can neutralize and protect animals against all three major disease-causing ebolaviruses. The findings, published online today in the journal Cell, could lead to the first broadly effective ebolavirus therapies and vaccines. Ebolaviruses infections are usually severe, and often fatal. There are no vaccines or treatments approved by the Food and Drug Administration for treating these viruses. Some two dozen ebolavirus outbreaks have occurred since 1976, when the first outbreak was documented in villages along the Ebola River in the Democratic Republic of Congo (formerly Zaire). The largest outbreak in history -- the 2013-16 Western African epidemic -- caused more than 11,000 deaths and infected more than 29,000 people. Monoclonal antibodies, which bind to and neutralize specific pathogens and toxins, have emerged as one of the most promising treatments for Ebola patients. A critical problem, however, is that most antibody therapies target just one specific ebolavirus. For example, the most advanced therapy -- ZMappTM, a cocktail of three monoclonal antibodies -- is specific for Ebola virus (formerly known as "Ebola Zaire"), but doesn't work against two related ebolaviruses (Sudan virus and Bundibugyo virus) that have also caused major outbreaks. "Since it's impossible to predict which of these agents will cause the next epidemic, it would be ideal to develop a single therapy that could treat or prevent infection caused by any known ebolavirus," says study co-leader Zachary A. Bornholdt, Ph.D., director of antibody discovery at Mapp Biopharmaceutical, Inc. "Our discovery and characterization of broadly neutralizing human antibodies is an important step toward that goal," adds study co-leader, Kartik Chandran, Ph.D. , professor of microbiology & immunology at Albert Einstein College of Medicine. The study was also co-led by John M. Dye, Ph.D., chief of viral immunology at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). In earlier research, Dr. Bornholdt and Laura M. Walker, Ph.D., a senior scientist at Adimab, LLC, isolated 349 distinct monoclonal antibodies from a survivor of the 2013-16 Ebola epidemic. In the current study, the multi-institutional research team found that two of those 349 antibodies, known as ADI-15878 and ADI-15742, potently neutralized infection by all five known ebolaviruses in tissue culture. Both antibodies were able to protect animals (mice and ferrets) that had been exposed to a lethal dose of the three major agents: Ebola virus, Bundibugyo virus and Sudan virus. Follow-up studies showed that the two antibodies isolated from the Ebola patient work by interfering with a critical step in the process by which ebolaviruses infect cells and then multiply inside them. The two antibodies encounter the virus while it's still in the bloodstream, and bind to glycoproteins (proteins to which carbohydrate chains are attached) that project from its surface. The virus, with its hitchhiking antibodies still bound to it, then attaches to a cell and enters the lysosome -- a membrane-bound structure within the cell that is filled with enzymes for digesting foreign and cellular components. The virus must then fuse with the lysosome membrane to escape into the host cell's cytoplasm, where it can multiply. However, the antibodies prevent the virus from breaking out of its lysosomal "prison," thus stopping infection in its tracks. "Knowing precisely where the antibodies attach to the glycoprotein molecules and when and how they act to neutralize ebolaviruses, we can begin to craft broadly effective immunotherapies," says Dr. Dye. "That knowledge has already allowed us to create a cocktail of monoclonal antibodies that we are testing in larger animal models for possible use in treating infected patients," adds Dr. Bornholdt. The researchers also pinpointed the human genes that are the likely source of the immune cells that produce the two antibodies. These and other findings could help speed the development of vaccines to prevent ebolavirus infection. "We'd like to synthesize vaccine immunogens [proteins that trigger antibody production] that can elicit the same types of broadly protective antibodies in people," says Dr. Chandran. The study is titled "Antibodies from a human survivor define sites of vulnerability for broad protection against ebolaviruses." Other Einstein researchers include co-first author Anna Z. Wec, M.S., Elisabeth K. Nyakatura, Ph.D., Jens Maximilian Fels, Rohit K. Jangra, Ph.D., M.V.Sc., B.V.Sc. & A.H., and Jonathan R. Lai, Ph.D. Additional contributors are co-first author Andrew S. Herbert, Ph.D., Rebekah M. James, and Russell R. Bakken, of USAMRIID, Fort Detrick, MD; Shihua He, Ph.D., Marc-Antoine de La Vega, Wenjun Zhu, Ph.D., and Xiangguo Qiu, M.D., of National Microbiology Laboratory, Public Health Agency of Canada and University of Manitoba, Manitoba, Canada; Charles D. Murin, Ph.D., Hannah L. Turner, and Andrew B. Ward, Ph.D. of The Scripps Research Institute, La Jolla, CA; Eileen Goodwin of Adimab, LLC, Lebanon, NH; and Dafna M. Abelson and Larry Zeitlin, Ph.D. of Mapp Biopharmaceutical Inc., San Diego, CA. The study was funded by grants from the National Institutes of Health (U19 AI109762), JSTO- Defense Threat Reduction Agency (CB4088 and HDTRA1-13-C-0018), and the Public Health Agency of Canada. The authors declare no financial conflicts of interest. Albert Einstein College of Medicine is one of the nation's premier centers for research, medical education and clinical investigation. During the 2016-2017 academic year, Einstein is home to 717 M.D. students, 166 Ph.D. students, 103 students in the combined M.D./Ph.D. program, and 278 postdoctoral research fellows. The College of Medicine has more than 1,900 full-time faculty members located on the main campus and at its clinical affiliates. In 2016, Einstein received more than $160 million in awards from the National Institutes of Health (NIH). This includes the funding of major research centers at Einstein in aging, intellectual development disorders, diabetes, cancer, clinical and translational research, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. Einstein runs one of the largest residency and fellowship training programs in the medical and dental professions in the United States through Montefiore and an affiliation network involving hospitals and medical centers in the Bronx, Brooklyn and on Long Island. For more information, please visit, read our blog, follow us on Twitter, like us on Facebook and view us on YouTube . Mapp Biopharmaceutical develops monoclonal antibody products for the prevention and treatment of infectious diseases, focusing on unmet needs in global health and biodefense. The company has advanced two anti-viral antibody-based therapeutics into clinical trials, including a Phase 2 trial of ZMappTM in patients with Ebola Virus Disease. For more information, visit http://www. About U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) USAMRIID's mission is to provide leading edge medical capabilities to deter and defend against current and emerging biological threat agents. Research conducted at USAMRIID leads to medical solutions-vaccines, drugs, diagnostics, and information-that benefit both military personnel and civilians. The Institute plays a key role as the lead military medical research laboratory for the Defense Threat Reduction Agency's Joint Science and Technology Office for Chemical and Biological Defense. USAMRIID is a subordinate laboratory of the U.S. Army Medical Research and Materiel Command. For more information, visit http://www. .


News Article | May 18, 2017
Site: www.prnewswire.com

Monoclonal antibodies, which bind to and neutralize specific pathogens and toxins, have emerged as one of the most promising treatments for Ebola patients. A critical problem, however, is that most antibody therapies target just one specific ebolavirus. For example, the most advanced therapy—ZMappTM, a cocktail of three monoclonal antibodies—is specific for Ebola virus (formerly known as "Ebola Zaire"), but doesn't work against two related ebolaviruses (Sudan virus and Bundibugyo virus) that have also caused major outbreaks. "Since it's impossible to predict which of these agents will cause the next epidemic, it would be ideal to develop a single therapy that could treat or prevent infection caused by any known ebolavirus," says study co-leader Zachary A. Bornholdt, Ph.D., director of antibody discovery at Mapp Biopharmaceutical, Inc. "Our discovery and characterization of broadly neutralizing human antibodies is an important step toward that goal," adds study co-leader, Kartik Chandran, Ph.D., professor of microbiology & immunology at Albert Einstein College of Medicine. The study was also co-led by John M. Dye, Ph.D., chief of viral immunology at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). In earlier research, Dr. Bornholdt and Laura M. Walker, Ph.D., a senior scientist at Adimab, LLC, isolated 349 distinct monoclonal antibodies from a survivor of the 2013-16 Ebola epidemic. In the current study, the multi-institutional research team found that two of those 349 antibodies, known as ADI-15878 and ADI-15742, potently neutralized infection by all five known ebolaviruses in tissue culture. Both antibodies were also able to protect animals (mice and ferrets) that had been exposed to a lethal dose of the three major agents: Ebola virus, Bundibugyo virus and Sudan virus. Follow-up studies showed that the two antibodies isolated from the Ebola patient work by interfering with a critical step in the process by which ebolaviruses infect cells and then multiply inside them. The two antibodies encounter the virus while it's still in the bloodstream, and bind to glycoproteins (proteins to which carbohydrate chains are attached) that project from its surface. The virus, with its hitchhiking antibodies still bound to it, then attaches to a cell and enters the lysosome— a membrane-bound structure within the cell that is filled with enzymes for digesting foreign and cellular components. The virus must then fuse with the lysosome membrane to escape into the host cell's cytoplasm, where it can multiply. However, the antibodies prevent the virus from breaking out of its lysosomal "prison," thus stopping infection in its tracks. "Knowing precisely where the antibodies attach to the glycoprotein molecules and when and how they act to neutralize ebolaviruses, we can begin to craft broadly effective immunotherapies," says Dr. Dye. "That knowledge has already allowed us to create a cocktail of monoclonal antibodies that we are testing in larger animal models for possible use in treating infected patients," adds Dr. Bornholdt. Dr. Chandran explains more about the findings in this video at http://www.einstein.yu.edu/gadgets/video/dcpa/?video=kartik-chandran-ebola The researchers also pinpointed the human genes that are the likely source of the immune cells that produce the two antibodies. These and other findings could help speed the development of vaccines to prevent ebolavirus infection. "We'd like to synthesize vaccine immunogens [proteins that trigger antibody production] that can elicit the same types of broadly protective antibodies in people," says Dr. Chandran. The study is titled "Antibodies from a human survivor define sites of vulnerability for broad protection against ebolaviruses." Other Einstein researchers include co-first author Anna Z. Wec, M.S., Elisabeth K. Nyakatura, Ph.D., Jens Maximilian Fels, Rohit K. Jangra, Ph.D., M.V.Sc., B.V.Sc. & A.H., and Jonathan R. Lai, Ph.D. Additional contributors are co-first author Andrew S. Herbert, Ph.D., Rebekah M. James, and Russell R. Bakken, of USAMRIID, Fort Detrick, MD; Shihua He, Ph.D., Marc-Antoine de La Vega, Wenjun Zhu, Ph.D., and Xiangguo Qiu, M.D., of National Microbiology Laboratory, Public Health Agency of Canada and University of Manitoba, Manitoba, Canada; Charles D. Murin, Ph.D., Hannah L. Turner, and Andrew B. Ward, Ph.D. of The Scripps Research Institute, La Jolla, CA; Eileen Goodwin of Adimab, LLC, Lebanon, NH; and Dafna M. Abelson and Larry Zeitlin, Ph.D. of Mapp Biopharmaceutical Inc., San Diego, CA. The study was funded by grants from the National Institutes of Health (U19 AI109762), JSTO- Defense Threat Reduction Agency (CB4088 and HDTRA1-13-C-0018), and the Public Health Agency of Canada. The authors declare no financial conflicts of interest. Albert Einstein College of Medicine is one of the nation's premier centers for research, medical education and clinical investigation. During the 2016-2017 academic year, Einstein is home to 717 M.D. students, 166 Ph.D. students, 103 students in the combined M.D./Ph.D. program, and 278 postdoctoral research fellows. The College of Medicine has more than 1,900 full-time faculty members located on the main campus and at its clinical affiliates. In 2016, Einstein received more than $160 million in awards from the National Institutes of Health (NIH). This includes the funding of major research centers at Einstein in aging, intellectual development disorders, diabetes, cancer, clinical and translational research, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. Einstein runs one of the largest residency and fellowship training programs in the medical and dental professions in the United States through Montefiore and an affiliation network involving hospitals and medical centers in the Bronx, Brooklyn and on Long Island. For more information, please visit www.einstein.yu.edu, read our blog, follow us on Twitter, like us on Facebook and view us on YouTube. Mapp Biopharmaceutical develops monoclonal antibody products for the prevention and treatment of infectious diseases, focusing on unmet needs in global health and biodefense. The company has advanced two anti-viral antibody-based therapeutics into clinical trials, including a Phase 2 trial of ZMappTM in patients with Ebola Virus Disease. For more information, visit www.mappbio.com About U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) USAMRIID's mission is to provide leading edge medical capabilities to deter and defend against current and emerging biological threat agents. Research conducted at USAMRIID leads to medical solutions-vaccines, drugs, diagnostics, and information-that benefit both military personnel and civilians. The Institute plays a key role as the lead military medical research laboratory for the Defense Threat Reduction Agency's Joint Science and Technology Office for Chemical and Biological Defense. USAMRIID is a subordinate laboratory of the U.S. Army Medical Research and Materiel Command. For more information, visit www.usamriid.army.mil To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/researchers-discover-first-human-antibodies-that-work-against-all-ebolaviruses-300460154.html


The team of investigators immunized a macaque with a special cocktail of engineered proteins mimicking the surface glycoproteins of ebolaviruses to induce broadly protective responses.  The scientists then screened immune cells of the vaccinated animal to specifically isolate those monoclonal antibodies that reacted to multiple ebolaviruses.  After searching through millions of immune cells, a cross-reactive antibody (CA45) was isolated that was able to neutralize cellular infection by all pathogenic ebolaviruses. CA45, when given to already infected rodents at the peak of their disease, was able to protect the animals from the otherwise lethal infection.  The scientists then combined CA45 with another antibody they discovered previously and demonstrated that the combination showed superior activity, protecting mice, guinea pigs and ferrets from infections with Ebola, Sudan, and Bundibugyo viruses with almost no sign of disease. This is the first time a therapeutic agent has been able to fully protect animals against all three pathogenic ebolaviruses. The glycoprotein (GP) on the surface of the ebolavirus is responsible for entry into the cells.  The entry process involves first interaction with the cell surface followed by transport to specialized cellular compartments called endosomes where GP interacts with its cellular receptor.  Finally the GP mediates the last step of entry, the fusion of the viral and endosomal membrane that allows the virus to release its content into the cells.  Using a variety of methods the team identified the specific region of ebolavirus GP that is attacked by CA45.  This region is within the so-called fusion loop that mediates fusion of the viral and endosomal membrane.  The site attacked by CA45 has a remarkably similar structure in the GP of various ebolaviruses, explaining its ability to cross protect against multiple viruses.  Recently similar broadly neutralizing antibodies targeting the fusion domain of HIV and influenza have been discovered indicating that this region is a key site of vulnerability for these viruses. The fact that such a broadly protective antibody was elicited by immunization with an engineered vaccine suggests the feasibility of developing a vaccine protective against multiple ebolaviruses.  "With every new antibody we learn a little more about this virus and how it can be attacked," says Dr. M. Javad Aman of Integrated BioTherapeutics and a senior author on the paper.  He went on to say "We are carefully analyzing this information to devise strategies to make a single vaccine effective against all ebolaviruses-- such a vaccine may be entirely within reach now." "We are on our way to designing novel vaccines and immunotherapeutics for broader protection against all pathogenic ebolaviruses, with the insights we have been gaining," says Dr. Yuxing Li, Associate Professor of IBBR and the co-corresponding author of the paper. The paper is titled "Immunization-elicited Broadly Protective Antibody Reveals Ebolavirus Fusion Loop as a Site of Vulnerability." In addition to Drs. Li and Aman and the co-first authors Drs. Xuelian Zhao and Katie A. Howell, contributors include Shihua He, Jennifer M. Brannan, Anna Z. Wec, Edgar Davidson, Hannah L. Turner, Chi-I Chiang, Lin Lei, J. Maximilian Fels, Hong Vu, Sergey Shulenin, Ashley N. Turonis, Ana I. Kuehne, Guodong Liu, Mi Ta, Yimeng Wang, Christopher Sundling, Yongli Xiao, Jennifer S. Spence, Benjamin J. Doranz, Frederick W. Holtsberg, Andrew B. Ward, Kartik Chandran, John M. Dye, and Xiangguo Qiu. This work was supported by a contract (HDTRA1-13-C-0015) from US Defense Threat Reduction Agency (DTRA) and NIAID/NIH grants R43AI124765, R01AI126587, U19AI109762, Intramural Research Award from IBBR, University of Maryland, NIAID contract HHSN272201400058C, JSTO-DTRA project CB4077, and also partially supported by Public Health Agency of Canada (PHAC). IBT is a biotechnology company focused on the discovery of novel vaccines and therapies for emerging infectious diseases with a pipeline that includes promising product candidates for bacterial and viral infections including unique pan-filovirus immunotherapeutics and vaccines, vaccines for Staphylococcal infections, and a variety of other product candidates for emerging viruses.  Located in Rockville, MD, IBT has a close working relationship with United States Government agencies including the National Institute of Allergy and Infectious Diseases (NIAID/NIH). National Cancer Research Institute (NCI), Department of Defense (DOD), United States Army Medical Research Institute of Infection Diseases (USAMRIID) as well as many biotechnology and pharmaceutical companies and academic laboratories.  For more information, visit www.integratedbiotherapeutics.com. About the Institute for Bioscience and Biotechnology Research (IBBR) IBBR is a University System of Maryland joint research enterprise among the University of Maryland College Park, the University of Maryland Baltimore, and the National Institute of Standards and Technology.  With a long-standing scientific focus on structure-function relationships of biomolecules, genetic systems, and applications, e.g., vaccines, therapeutics, drug delivery technologies, and biomanufacturing, IBBR's mission is to leverage its unique capabilities and infrastructure to marshal innovative technologies and expertise across its partnering institutions, to foster integrated, cross-disciplinary team approaches to scientific research and education, and to pursue translational programs and projects aimed at advancing innovations to commercialization in real world applications. The Institute also serves to expand the economic base of science and technology in the state of Maryland and at the national level. For more information visit http://www.ibbr.umd.edu/ USAMRIID's mission is to provide leading edge medical capabilities to deter and defend against current and emerging biological threat agents. Research conducted at USAMRIID leads to medical solutions-vaccines, drugs, diagnostics, and information-that benefit both military personnel and civilians. The Institute plays a key role as the lead military medical research laboratory for the Defense Threat Reduction Agency's Joint Science and Technology Office for Chemical and Biological Defense. USAMRIID is a subordinate laboratory of the U.S. Army Medical Research and Materiel Command. For more information, visit www.usamriid.army.mil Albert Einstein College of Medicine is one of the nation's premier centers for research, medical education and clinical investigation. During the 2016-2017 academic year, Einstein is home to 717 M.D. students, 166 Ph.D. students, 103 students in the combined M.D./Ph.D. program, and 278 postdoctoral research fellows. The College of Medicine has more than 1,900 full-time faculty members located on the main campus and at its clinical affiliates. In 2016, Einstein received more than $160 million in awards from the National Institutes of Health (NIH). This includes the funding of major research centers at Einstein in aging, intellectual development disorders, diabetes, cancer, clinical and translational research, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. Einstein runs one of the largest residency and fellowship training programs in the medical and dental professions in the United States through Montefiore and an affiliation network involving hospitals and medical centers in the Bronx, Brooklyn and on Long Island. For more information, please visit www.einstein.yu.edu. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/immunization-elicited-antibody-shows-universal-protection-against-multiple-ebolaviruses-300459398.html


News Article | May 19, 2017
Site: www.sciencedaily.com

After analyzing the blood of a survivor of the 2013-16 Ebola outbreak, a team of scientists from academia, industry and the government has discovered the first natural human antibodies that can neutralize and protect animals against all three major disease-causing ebolaviruses. The findings, published online in the journal Cell, could lead to the first broadly effective ebolavirus therapies and vaccines. Ebolaviruses infections are usually severe, and often fatal. There are no vaccines or treatments approved by the Food and Drug Administration for treating these viruses. Some two dozen ebolavirus outbreaks have occurred since 1976, when the first outbreak was documented in villages along the Ebola River in the Democratic Republic of Congo (formerly Zaire). The largest outbreak in history -- the 2013-16 Western African epidemic -- caused more than 11,000 deaths and infected more than 29,000 people. Monoclonal antibodies, which bind to and neutralize specific pathogens and toxins, have emerged as one of the most promising treatments for Ebola patients. A critical problem, however, is that most antibody therapies target just one specific ebolavirus. For example, the most advanced therapy -- ZMappTM, a cocktail of three monoclonal antibodies -- is specific for Ebola virus (formerly known as "Ebola Zaire"), but doesn't work against two related ebolaviruses (Sudan virus and Bundibugyo virus) that have also caused major outbreaks. "Since it's impossible to predict which of these agents will cause the next epidemic, it would be ideal to develop a single therapy that could treat or prevent infection caused by any known ebolavirus," says study co-leader Zachary A. Bornholdt, Ph.D., director of antibody discovery at Mapp Biopharmaceutical, Inc. "Our discovery and characterization of broadly neutralizing human antibodies is an important step toward that goal," adds study co-leader, Kartik Chandran, Ph.D. , professor of microbiology & immunology at Albert Einstein College of Medicine. The study was also co-led by John M. Dye, Ph.D., chief of viral immunology at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). In earlier research, Dr. Bornholdt and Laura M. Walker, Ph.D., a senior scientist at Adimab, LLC, isolated 349 distinct monoclonal antibodies from a survivor of the 2013-16 Ebola epidemic. In the current study, the multi-institutional research team found that two of those 349 antibodies, known as ADI-15878 and ADI-15742, potently neutralized infection by all five known ebolaviruses in tissue culture. Both antibodies were able to protect animals (mice and ferrets) that had been exposed to a lethal dose of the three major agents: Ebola virus, Bundibugyo virus and Sudan virus. Follow-up studies showed that the two antibodies isolated from the Ebola patient work by interfering with a critical step in the process by which ebolaviruses infect cells and then multiply inside them. The two antibodies encounter the virus while it's still in the bloodstream, and bind to glycoproteins (proteins to which carbohydrate chains are attached) that project from its surface. The virus, with its hitchhiking antibodies still bound to it, then attaches to a cell and enters the lysosome -- a membrane-bound structure within the cell that is filled with enzymes for digesting foreign and cellular components. The virus must then fuse with the lysosome membrane to escape into the host cell's cytoplasm, where it can multiply. However, the antibodies prevent the virus from breaking out of its lysosomal "prison," thus stopping infection in its tracks. "Knowing precisely where the antibodies attach to the glycoprotein molecules and when and how they act to neutralize ebolaviruses, we can begin to craft broadly effective immunotherapies," says Dr. Dye. "That knowledge has already allowed us to create a cocktail of monoclonal antibodies that we are testing in larger animal models for possible use in treating infected patients," adds Dr. Bornholdt. The researchers also pinpointed the human genes that are the likely source of the immune cells that produce the two antibodies. These and other findings could help speed the development of vaccines to prevent ebolavirus infection. "We'd like to synthesize vaccine immunogens [proteins that trigger antibody production] that can elicit the same types of broadly protective antibodies in people," says Dr. Chandran.


News Article | May 24, 2017
Site: www.eurekalert.org

A new study by a multi-national research team, including scientists from the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), explains how Zika virus entered the United States last year and how it might re-enter the country this year. The study was published online today in the journal Nature. In July 2016, mosquito-borne Zika virus transmission was first reported in the continental U.S. and since then, hundreds of locally-acquired infections have been reported in Florida. Through the Laboratory Response Network, scientists at USAMRIID and the Florida Department of Health (FLDOH) joined forces to understand how the virus entered and was spreading in Florida. They did this through near real-time genomic sequencing. Viral genome sequences were released publically, as they were generated, to help other scientists studying the Zika virus disease outbreak, many of whom are co-authors of this study. According to Jason Ladner, Ph.D., a scientist at USAMRIID and one of the study's co-lead authors, by sequencing the virus's genome from human and mosquito infections, the team created a "family tree" showing how the virus spread through space and time. They discovered that the Zika virus disease outbreak in Florida was actually the result of multiple independent introduction events, the earliest of which occurred in the spring of 2016, several months before initial detection. "There is a reason why the first local Zika virus infections in the U.S. occurred in Florida," says Ladner. Florida is home to year-round populations of Aedes aegypti mosquitoes, the main species that transmits Zika virus to humans, and Miami is a significant travel hub, with more international air and sea traffic than any other city in the continental United States in 2016. However, the researchers show that sustained transmission of Zika virus in Florida is unlikely, making future outbreaks dependent on re-introductions of the virus. Their study also highlights the success of localized mosquito control efforts in preventing further spread of the virus in Florida. More broadly, the research illustrates the importance of establishing a robust capability for rapidly responding to emerging disease threats -- not just Zika virus. "Essentially, the sequencing approach that we used for this study is the first step and one of the most critical pieces of that capability," said Gustavo Palacios, Ph.D., a co-senior author on the paper and director of the Center for Genome Sciences at USAMRIID. Palacios and his colleagues had previously used genome sequencing technology to track the movement of Ebola virus in near real-time during the 2013-2016 outbreak in Western Africa. Their findings helped to shape outbreak response and disease control efforts on the ground. When Zika virus, which is carried by mosquitoes and has been linked to severe birth defects, entered the United States last year, his team put the same tools to work in an effort to track the virus's spread. According to Palacios, the recent outbreaks of Ebola and Zika virus disease underscore the need for a rapid and cohesive strategy to interrupt epidemics. Traditional research and development approaches rely on an academic model, with timelines that do not lend themselves to a prompt response. In addition, an integrated approach that allows for sharing of resources across agencies is critically important. USAMRIID and its partners have proposed to develop a platform called Accelerated Defense against Emerging Pathogen Threats (ADEPT) to provide a logical and effective plan for rapidly developing medical countermeasures. "The ADEPT platform was designed with a clear goal -- to quickly generate the information and medical countermeasures needed to stop an epidemic," Palacios said. "It provides a strong foundation with multiple parallel research and development efforts under one organizational structure." In addition, he said, ADEPT is not based on a specific type of medical countermeasure, but rather on the generation of information that will result in the development of the most appropriate product for any emerging disease outbreak. At the same time, it is vital that the information collected and generated by ADEPT is immediately available to the entire scientific community involved in the outbreak response. Consequently, ADEPT is completely open access and data will be shared in real time with the World Health Organization (WHO), the Coalition for Epidemic Preparedness Innovations (CEPI), and the affected nations. An independent scientific panel convened by the WHO evaluated and selected ADEPT as a platform that could positively impact biological preparedness under the WHO Research and Development Blueprint. The panel's report is available at http://www. . The Nature study was a collaboration of more than 60 scientists from nearly 20 institutions, including study co-leaders at the Scripps Research Institute, the Florida Department of Health, Florida Gulf Coast University, the University of Oxford, the Fred Hutchinson Cancer Research Center, and the Broad Institute of MIT and Harvard. It also included authors from the University of Miami, the University of Birmingham, Colorado State University, St. Michael's Hospital (Toronto), the University of Toronto, the University of Washington, Tulane University, Miami-Dade County Mosquito Control, the University of Florida, the University of Edinburgh and the National Institutes of Health. USAMRIID's mission is to provide leading edge medical capabilities to deter and defend against current and emerging biological threat agents. Research conducted at USAMRIID leads to medical solutions-vaccines, drugs, diagnostics, and information-that benefit both military personnel and civilians. The Institute plays a key role as the lead military medical research laboratory for the Defense Threat Reduction Agency's Joint Science and Technology Office for Chemical and Biological Defense. USAMRIID is a subordinate laboratory of the U.S. Army Medical Research and Materiel Command. For more information, visit http://www. . Reference: Genomic epidemiology reveals multiple introductions of Zika virus into the United States. N.D. Grubaugh et al. DOI: 10.1038/nature22400. Funding: ZIKV sequencing at USAMRIID was supported by the Defense Advanced Research Projects Agency.


BOSTON, March 02, 2017 (GLOBE NEWSWIRE) -- Paratek Pharmaceuticals, Inc. (Nasdaq:PRTK), a biopharmaceutical company focused on the development and commercialization of innovative therapies based upon tetracycline chemistry, today reported financial results for the full year and quarter ended December 31, 2016. "We made excellent progress with the clinical development program of omadacycline in the fourth quarter and continued our work to prepare for a potential NDA submission in the first half of 2018,” said Michael Bigham, Chairman and Chief Executive Officer, Paratek. “With the enrollment of the pneumonia study now complete, we expect to release top-line data early in the second quarter. Our Phase 3 study of an oral-only dosing regimen in skin infections is progressing well.  We continue to expect top-line data as early as the second quarter of this year from this study.” Fourth Quarter and Full Year 2016 Financial Results For the fourth quarter of 2016, Paratek reported a net loss of $26.5 million, or $1.16 per share, compared to a net loss of $21.1 million, or $1.20 per share, for the same period in 2015.  For the year ended December 31, 2016, Paratek reported a net loss of $111.6 million, or $5.51 per share, compared to a net loss of $70.9 million, or $4.29 per share, for the same period in 2015. Research and development expenses were $19.7 million and $83.5 million for the quarter and year ended December 31, 2016, respectively, compared to $15.2 million and $50.8 million for the same periods in 2015. The increase in research and development expense for the year ended December 31, 2016 was primarily the result of ongoing development of omadacycline, including costs associated with clinical studies for the treatment of ABSSSI, CABP and UTI, production of omadacycline registration batches and manufacturing process validation work, other research and development activities, and employee compensation. General and administrative expenses were $6.5 million and $26.4 million for the quarter and year ended December 31, 2016, respectively, compared to $5.6 million and $20.0 million for the same periods in 2015.  The increase in general and administrative costs was primarily the result of employee compensation. As of December 31, 2016, Paratek had cash, cash equivalents, and marketable securities of $128.0 million. Based on current assumptions, Paratek’s cash, cash equivalents and marketable securities will enable the Company to fund operating expenses and capital expenditure requirements through the first half of 2018. Paratek initiated sales of shares under a Controlled Equity Offering Sales Agreement with Cantor Fitzgerald & Co. in March 2016, and sold an aggregate of 860,014 shares of common stock through December 31, 2016, resulting in net proceeds of $11.6 million.  As of February 24, 2017, an additional 870,078 shares were sold under the Sales Agreement subsequent to December 31, 2016, resulting in net proceeds of $13.1 million, which will be recognized during the first quarter of 2017. Conference Call and Webcast Paratek’s earnings conference call for the quarter ended December 31, 2016, will be broadcast at 8:30 a.m. EST on March 2, 2017. The live webcast can be accessed under "Events and Presentations" in the Investor Relations section of Paratek’s website at www.paratekpharma.com. Domestic investors wishing to participate in the call should dial 877-407-9039 and international investors should dial 201-689-8470. The conference ID is 13656270. Investors can also access the call at http://public.viavid.com/index.php?=123110. Replays of the call will be available through March 16, 2017. Domestic investors can access the replay by dialing 844-512-2921 and international investors can access the replay by dialing 412-317-6671. The PIN code to access the replay is 13656270. Website Information Paratek routinely posts important information for investors on the Investor Relations section of its website at www.paratekpharma.com. Paratek intends to use this website as a means of disclosing material, non-public information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor the Investor Relations section of Paratek’s website, in addition to following its press releases, SEC filings, public conference calls, presentations and webcasts. The information contained on, or that may be accessed through, Paratek’s website is not incorporated by reference into, and is not a part of, this document. About Paratek Pharmaceuticals, Inc. Paratek Pharmaceuticals, Inc. is a biopharmaceutical company focused on the development and commercialization of innovative therapies based upon its expertise in novel tetracycline chemistry. Paratek's lead product candidate, omadacycline, is the first in a new class of tetracyclines known as aminomethylcyclines, with broad-spectrum activity against Gram-positive, Gram-negative and atypical bacteria. In June 2016, Paratek announced positive efficacy data in a Phase 3 registration study in acute bacterial skin and skin structure infections (ABSSSI) demonstrating the efficacy and safety of intravenous (IV) to once-daily oral omadacycline compared to linezolid.  A Phase 3 registration study for community-acquired bacterial pneumonia (CABP) comparing IV-to-once-daily oral omadacycline to IV-to-oral moxifloxacin was initiated in November 2015 and completed enrollment in January 2017. Paratek will report top-line data from this study early in the second quarter of 2017. A Phase 3 registration study in ABSSSI comparing once-daily oral-only dosing of omadacycline to twice-daily oral-only dosing of linezolid was initiated in August 2016.  Top-line data from this study are expected as early as the second quarter of 2017.  A Phase 1B study in uncomplicated urinary tract infections (UTI) was initiated in May 2016 and positive top-line PK proof-of-principle data were reported in November 2016.  The company plans to begin enrolling patients in a proof-of-concept Phase 2 study in complicated UTI as early as the fourth quarter of 2017. Omadacycline has been granted Qualified Infectious Disease Product designation and Fast Track status by the U.S. Food and Drug Administration for several indications. In October 2016, Paratek announced a new cooperative research effort with the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) to study omadacycline against pathogenic agents causing infectious diseases of public health and biodefense importance. These studies are designed to confirm dosing regimens and assess efficacy of omadacycline against biodefense pathogens, including Yersinia pestis (plague) and Bacillus anthracis (anthrax). Omadacycline is a new once-daily oral and IV, well-tolerated broad spectrum antibiotic being developed for use as empiric monotherapy for patients suffering from serious community-acquired bacterial infections, such as acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, urinary tract infections and other community-acquired bacterial infections, particularly when antibiotic resistance is of concern to prescribing physicians. Paratek's second Phase 3 product candidate, sarecycline, is a well-tolerated, once-daily, oral, narrow spectrum tetracycline-derived antibiotic with potent anti-inflammatory properties for the potential treatment of acne and rosacea in the community setting.  Allergan owns the U.S. rights for the development and commercialization of sarecycline. Paratek retains all ex-U.S. rights.  Allergan initiated two identical Phase 3 registration studies in December 2014 for sarecycline for the treatment of moderate to severe acne vulgaris. Top-line Phase 3 data are expected in the first half of 2017. Forward Looking Statements This press release contains forward-looking statements including statements related to our overall strategy, product candidates, clinical studies, cash resources, prospects and expected results, including statements about the timing of advancing omadacycline and otherwise preparing for clinical studies, the potential for omadacycline to serve as an empiric monotherapy treatment option for patients suffering from ABSSSI, CABP, UTI, and other bacterial infections when resistance is of concern, the prospect of omadacycline providing broad-spectrum activity, and our having the resources to execute on our clinical studies. All statements, other than statements of historical facts, included in this press release are forward-looking statements, and are identified by words such as "advancing," "believe," "expect," "well positioned," "look forward," "anticipated," "continued," and other words and terms of similar meaning. These forward-looking statements are based upon our current expectations and involve substantial risks and uncertainties. We may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in our forward-looking statements and you should not place undue reliance on these forward-looking statements. Our actual results and the timing of events could differ materially from those included in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks related to (i) our need for substantial additional funding to complete the development and commercialization of our product candidates, (ii) our ability to raise the capital to do so, (iii) our ability to develop and manufacture our drug candidates for potential commercialization, (iv) the advancement of omadacycline Phase 3 studies for ABSSSI, (v) the potential for omadacycline to be successfully developed for use as an empiric monotherapy for patients suffering from serious community-acquired bacterial infections, (vi) the potential of omadacycline to become the primary antibiotic choice of physicians for the treatment of serious community-acquired bacterial infections, (vii) the potential use and effectiveness of sarecycline for the treatment of acne and rosacea in the community setting, and (viii) the timing of the Phase 3 program in moderate-severe acne for sarecycline, risks that data to date and trends may not be predictive of future results, risks related to the conduct of our clinical studies, and risks that our clinical studies and product candidates do not receive regulatory approval. These and other risk factors are discussed under "Risk Factors" and elsewhere in our Annual Report on Form 10-K for the year ended December 31, 2016, and our other filings with the Securities and Exchange Commission. We expressly disclaim any obligation or undertaking to update or revise any forward-looking statements contained herein.


PHILADELPHIA & ROCKVILLE, Md.--(BUSINESS WIRE)--Integral Molecular and Integrated BioTherapeutics have teamed up in the fight against the global health crises posed by Ebola and Zika viruses, signing a collaborative vaccine discovery agreement to help eradicate these threats. The two companies will leverage their complementary technologies to produce vaccine candidates that are specifically engineered to generate a maximally protective immune response in humans. The availability of such vaccines will prevent the recurrence of the deadly 2014-2016 Ebola epidemic that killed over 11,000 people in West Africa, and has the potential to curtail the spread of the ongoing Zika virus epidemic associated with severe fetal brain defects. Integral Molecular is an industry leader in the study of complex membrane proteins such as viral Envelope proteins. The company will use its proprietary Shotgun Mutagenesis protein engineering technology to generate and screen large panels of Envelope protein variants to identify an optimized protein that could serve as a highly immunogenic and protective vaccine, and will ultimately apply its high-resolution epitope mapping technologies to characterize the vaccine’s protective effects. Integrated BioTherapeutics, a leader in infectious disease research, will conduct preclinical studies to test the efficacy of vaccine candidates in disease models. “The vulnerability of human populations during the recent Ebola and Zika outbreaks highlighted the consequences of the lack of effective vaccines against these pathogens. The goal of our collaboration is to meet these concerns by creating efficacious vaccine candidates based on viral Envelope proteins,” said M. Javad Aman, President and CEO of Integrated BioTherapeutics. “We look forward to working with Integrated BioTherapeutics. Their experience in the development of a pipeline of antiviral products based on rationally designed and engineered viral proteins and antibodies will be a tremendous asset in our joint efforts towards producing Ebola and Zika vaccines,” continued Benjamin Doranz, President and CEO of Integral Molecular. Thus far, the two companies have engaged in highly successful collaborative research that has culminated in the pursuit of these vaccine candidates. This includes the development and characterization of the protective and cross-neutralizing pan-Ebola antibody FVM04, recently published in Cell Reports (Howell et al., 2016). Additional research resulting from this collaboration is expected to be published later this year. Integral Molecular is a research-driven biotechnology company creating innovative technologies and a pipeline of therapeutic antibodies against under-exploited membrane protein targets, including GPCRs, ion channels, transporters, and viral envelopes. This platform is built on the company’s Lipoparticle and Shotgun Mutagenesis technologies and over 15 years of experience optimizing membrane proteins. Integral Molecular discovers antibodies for partners in parallel with its own independent work developing antibodies for licensing. The company currently has therapeutic programs focused on pain, immunity, and infectious diseases. For more information, visit www.integralmolecular.com. IBT is a biotechnology company focused on the discovery of novel vaccines and therapeutics for emerging infectious diseases with a pipeline that includes promising product candidates for bacterial and viral infections including unique pan-filovirus monoclonal antibodies and vaccine candidates and a variety of other engineered product candidates for emerging viruses. IBT also operates a testing service business (www.ibtbioservices.com) focused on in vitro and in vivo models for viral agents such as Zika, dengue, yellow fever, influenza and RSV as wells as bacterial agents such as S. aureus, S. pneumoniae, E. Coli, and C. difficile. Located in Rockville, Maryland, IBT has a close working relationship with United States Government agencies including the National Institute of Allergy and Infectious Diseases (NIAID/NIH), National Cancer Institute (NCI), Department of Defense (DOD), United States Army Medical Research Institute of Infectious Diseases (USAMRIID) as well as many biotechnology and pharmaceutical companies and academic laboratories. For more information, visit www.integratedbiotherapeutics.com.


"Until now, multicomponent viruses were thought to infect only plants and fungi, as a result of relatively inefficient transmission," says first author Jason Ladner, a staff scientist from the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). "Our finding that these viruses are present in mosquitoes is going to challenge us to re-evaluate some of our assumptions about them." Multicomponent viruses use a method of transmission that's different from other viruses known to infect animals. Instead of being contained in a single viral particle, their genomes are segmented and encapsulated among multiple particles. A yellow fever virus, for example, has all its genetic material packaged into a single particle. Therefore, one particle is enough to infect a cell. But in order for a multicomponent virus to establish an infection, the cell has to get infected with at least one particle of each type. The research is part of a global effort to monitor and prepare for outbreaks of unknown viral diseases. Mosquitoes and other insects can act as vectors for viral diseases, carrying them from place to place and transmitting them to human hosts via bites. Although the new virus does not appear to be a human pathogen, or even a mammalian one, the investigators say this work is a good exercise to help hone the tools and expertise needed to characterize novel infectious agents. In the study, the USAMRIID researchers worked with several other teams, including groups from the University of Texas Medical Branch and the New York State Department of Health, to isolate mosquitoes from different regions around the world. The newly discovered virus is named Guaico Culex after the Guaico region of Trinidad in which the mosquitoes that contained it were found. Guaico Culex was isolated by growing material obtained from the mosquitoes in cell culture. "This method has been useful particularly in finding new arboviruses, which are transmitted by mosquitoes and other arthropods to mammals," Ladner says. To identify arboviruses, cultures of mammalian cells are used. "We were also interested in viruses that may be found within mosquitoes but don't necessarily grow on mammalian cells, so we used cultures of insect cells, enabling us to find this new virus." Deep sequencing indicated that Guaico Culex belongs to a group of segmented viruses called Jingmenviruses, which were first discovered in 2014. In collaboration with a group at the University of Wisconsin-Madison, the USAMRIID researchers also showed for the first time evidence of a Jingmenvirus in the blood of a non-human primate, in this case a Ugandan red colobus monkey. This finding is also published in the current Cell Host & Microbe paper. Experts believe that the most likely infectious viruses to make the jump to humans are those that are already circulating in other mammals, especially non-human primates. Phylogenetic analysis indicated that this monkey virus shared a segmented common ancestor with Guaico Culex. However, researchers don't yet know if all Jingmenviruses are multicomponent like the Guaico Culex virus. It is also not known whether the Jingmenvirus isolated from the monkey had a pathogenic effect. "One of the things we're focused on at USAMRIID is rapid identification of pathogens from both clinical and environmental samples as well as characterization of novel viruses," says Gustavo Palacios, Director of the Center for Genome Sciences at USAMRIID and the study's senior author. "We're trying to make sure that we're not blindsided when the next virus comes around. With all of the diversity seen in these emerging viruses, we never know what the next one will be to have an impact on human health." Explore further: 'Good' mozzie virus might hold key to fighting human disease More information: Cell Host & Microbe, Ladner et al: "A Multicomponent Animal Virus Isolated from Mosquitoes" http://www.cell.com/cell-host-microbe/fulltext/S1931-3128(16)30310-9 , DOI: 10.1016/j.chom.2016.07.011

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