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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 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


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. .


Ebola virus infection can be detected in rhesus monkeys that survive the disease and no longer show symptoms, according to research published by Army scientists in today's online edition of the journal Nature Microbiology. The study sheds light on how the virus persists in certain areas of the body, and holds promise for the development of medical products to counter the disease in humans. During the 2013-2016 outbreak of Ebola virus disease in Western Africa, Ebola virus persistence in certain "immune privileged" sites--such as the eye, brain, and testes--became a significant concern. Survivors reported long-term effects such as loss of vision, headaches and joint pain, even after symptoms resolved. The virus also was shown to persist in seminal fluid and to have been transmitted through sexual intercourse. But until now, little was known about the mechanisms by which the virus entered these sites and escaped detection. To begin to answer those questions, Xiankun Zeng, Ph.D. and colleagues at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) analyzed archived tissues from rhesus monkeys that had previously been infected with Ebola virus to test experimental vaccines and treatments. "In the animals that showed an acute, or shortened, course of disease, the virus primarily replicated in the blood vessels," Zeng explained. "In those with a longer disease progression, the virus spread to surrounding tissues in the immune privileged sites. And in the survivors, we could see that the virus had migrated out of the blood vessels and into specific locations within immune privileged sites." The USAMRIID team was able to demonstrate persistent Ebola virus replication in the eye, brain, and testes of animals that survived the disease and no longer had symptoms. The survivors consisted of two groups--those that had received medical countermeasures, and those that survived infection with only supportive care. In the eye, the virus was found in macrophages that contain the protein CD68 in their surface, which could be where the virus "hides," according to the authors. They also showed that Ebola virus persists in the brain by breaking down the blood-brain barrier and causing inflammation. "This study lays the foundation for developing animal models of persistent Ebola virus infection in humans," Zeng commented. "What we observed in primates is quite similar to what happened during the outbreak--there were survivors with latent infection, but the virus was not detectable in the blood. This makes it much more difficult to contain the spread of the virus." In addition, the authors said, the study shows that otherwise promising experimental therapeutics may not clear the virus completely--suggesting that a different approach may be needed to develop medical countermeasures to Ebola virus. According to Zeng, the next step is to further develop this animal model and to evaluate potential treatments, especially small-molecule therapeutics, to prevent Ebola virus persistence. 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 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.


Tasso, Inc. (Tasso), Ceres Nanosciences (Ceres), George Mason University (Mason), and the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) today announced the commencement of a $11.7 million program, funded by the Defense Threat Reduction Agency (DTRA), to develop a reliable, safe, and simple universal surveillance platform for infectious disease outbreaks. During this multi-year program, which will be initiated with $4.25 million in funding from DTRA, Ceres will integrate its Nanotrap® particle technology, which can capture, concentrate, and preserve pathogens and other biomolecules, into Tasso's HemoLink™ device for simple and painless collection of large-volume capillary blood samples in remote environments. Tasso and Ceres will work in close collaboration with infectious disease experts and advanced biodefense laboratories at Mason and USAMRIID to develop an effective disease surveillance platform that can be rapidly deployed in the field, operated by untrained users, and improve early response. The platform will combine the Nanotrap® and HemoLink™ technologies to safely and reproducibly collect, preserve, and transport blood-borne pathogens. "Infectious diseases remain one of the main causes of death worldwide and a significant threat to national security," said Dr. Kylene Kehn-Hall of Mason. "In just the last five years, for example, epidemics of Ebola, Chikungunya, and Zika viruses, usually restricted to tropical climates, have reached the United States." "When a new outbreak occurs, public health officials quickly need as much information as possible about the pathogen(s) causing the outbreak to determine how to control it," said Dr. Louis Altamura of USAMRIID. "Analyzing clinical samples from infected patients is one of the best ways to get that information, but existing blood sample collection and screening methods can expose healthcare workers and laboratory technicians to pathogens, presenting safety concerns for these workers and potentially contributing to the spread of the epidemic." "We have demonstrated already that Nanotrap® particles can be used to enrich pathogens like influenza from biological samples and stabilize them for improved downstream analysis," said Ben Lepene, CTO of Ceres Nanosciences. "We're very excited to work with Tasso, Mason, and USAMRIID to apply that same approach to enrich and stabilize from blood a wide range of host biomarkers along with viral and bacterial pathogens that represent a risk to the U.S. Department of Defense." "There is an urgent need for an easier way to reach people in rural or hard-to-reach environments to provide health experts with the information they need to make effective decisions in a timely manner. Integrating the Nanotrap® particle technology and the simple HemoLink™ blood collection technology will enable acquiring samples from populations in outbreak regions without putting phlebotomists or patients at risk or requiring burdensome logistical networks," said Dr. Erwin Berthier, VP of R&D at Tasso. "The integrated device will be rapidly and safely deployable in any environment and will collect a large volume of capillary blood that can be shipped over long distances while retaining its clinical relevance." Tasso is a Seattle, WA, based startup focusing on improving healthcare and the diagnostics process by developing more accessible and convenient blood collection and shipping methods that can reach people in any location or environment. Tasso originated from technology developed in the University of Wisconsin-Madison and assembles a highly qualified team of biomedical engineers, hematology researchers, human-factor designers, and clinical experts that have successfully developed the HemoLink. The HemoLink was developed with funding from the National Institute for Minority Health and Health Disparities (NIMHD) and the Defense Advanced Research Projects Agency (DARPA). Tasso is an open and collaborative company that focuses on working with leading technological and clinical partners to deliver reliable and disruptive diagnostic innovations. Lean more at http://www. Ceres Nanosciences is a privately held company, located in Prince William County, Virginia, focused on the development of research and diagnostic products using its unique and proprietary Nanotrap® particle technology. The Nanotrap® particle technology provides powerful biomarker capture and biofluid sample processing capabilities for a wide array of diagnostic applications and sample handling needs. The Nanotrap® particle technology was invented at George Mason University and developed under funding from the National Institutes of Health (NIH). With support from the NIH, the Defense Advanced Research Projects Agency (DARPA), the Bill and Melinda Gates Foundation, and the Commonwealth of Virginia, Ceres is focused on incorporating this technology into a range of innovative diagnostic products. Learn more at http://www. George Mason University is Virginia's largest public research university. Located near Washington, D.C., Mason enrolls more than 36,000 students from 130 countries and all 50 states. Mason has grown rapidly over the past half-century and is recognized for its innovation and entrepreneurship, remarkable diversity, and commitment to accessibility. Mason is also one of the best values in higher education, producing graduates who lead all Virginia schools with the highest annual salaries. George Mason University's National Center for Biodefense and Infectious Diseases is a $50 million, 52,000-square-foot, stand-alone, high-security facility located adjacent to GMU's Prince William Campus in Manassas, Virginia. The facility features more than 18,500 square feet of lab space comprising BSL-2 open-design laboratories with cell culture suites, preparation areas, and a microscopy room; ABSL-2 rooms, a surgery suite; BSL-3 laboratories; and ABSL-3 suites and a necropsy suite. The facility is fully approved and licensed for select agent work by the Center for Disease Control and Prevention (CDC) and the U.S. Department of Agriculture (USDA). 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. . [The information contained in this press release does not necessarily reflect the position or the policy of the Government and no official endorsement should be inferred.]

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