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News Article | February 21, 2017
Site: www.eurekalert.org

In less than one year, researchers have developed multiple vaccine platforms that provide robust protection against Zika virus challenge in animal models BOSTON - As public health officials warn that spring's warmer temperatures may herald another increase of Zika virus infections in the Caribbean and North and South America, researchers around the world are racing to develop safe and effective measures to prevent the disease. In a review paper published today in the journal Immunity, a group of leading vaccine scientists -- including Dan H. Barouch, MD, PhD, of Beth Israel Deaconess Medical Center (BIDMC) -- outline advances in the hunt for a Zika vaccine and the challenges that still lie ahead. "The pace of preclinical and early clinical development for Zika vaccines is unprecedented," said Barouch, corresponding author and director of the Center for Virology and Vaccine Research at BIDMC. "In less than a year, our group and others have demonstrated that multiple vaccine platforms can provide robust protection against Zika virus challenge in animal models. However, unique challenges will need to be addressed in the clinical development of a Zika vaccine. " The recent outbreak of the Zika virus in the Americas began in Brazil nearly two years ago. By February 2016, the World Health Organization had declared the epidemic a global public health emergency, based largely on the virus' newly-established link to microcephaly and other major birth defects in babies born to infected mothers. The virus has also been associated with the neurologic disorder Guillain-Barré syndrome in adults. In a previously published paper, Barouch and colleagues, including Colonel Nelson L. Michael, MD, PhD, director of the Military HIV Research Program at the Walter Reed Army Institute of Research (WRAIR) and Stephen Thomas, MD, Upstate Medical University, State University of New York, demonstrated that three different vaccine candidates provided robust protection against Zika virus in both mice and rhesus monkeys. Several human clinical trials began last fall at test sites including BIDMC, WRAIR, and National Institute of Allergy and Infectious Diseases affiliated clinical trial sites. "The rapid advancement of Zika vaccine candidates into clinical trials reflects the uniquely focused and effective collaboration among scientists in the field to address this important global problem," said Barouch. Despite the accelerated pace of research, much remains unknown about the virus, raising unique challenges in developing a vaccine. Safety considerations are especially critical, given that the target population for a Zika vaccine would likely include men and women of childbearing age. Zika is a member of the flavivirus family of viruses, which includes West Nile virus, yellow fever virus, and dengue viruses, for which successful vaccines have been developed. Studies suggest that Zika-induced antibody responses may also cross-react with other flaviviruses, particularly dengue virus. Whether or not this antibody cross-reactivity may have clinical consequences is another consideration for Zika vaccines and requires further study. Co-authors include: Stephen J. Thomas, MD, Upstate Medical University, State University of New York, Syracuse; and Colonel Nelson L. Michael, MD, PhD, director, Military HIV Research Program, at Walter Reed Army Institute of Research (WRAIR). The review's authors acknowledge support from the U.S. Military Research and Material Command and the U.S. Military HIV Research Program; the National Institutes of Health (AI095985, AI096040, AI100663, AI124377); and the Ragon Institute of MGH, MIT, and Harvard. Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www. .


News Article | November 10, 2016
Site: www.eurekalert.org

Silver Spring, Md. - Researchers have found that an investigational treatment combining a therapeutic vaccine and an immune stimulator improves virologic control and delays viral rebound following the discontinuation of antiretroviral therapy (ART) in non-human primates infected with SIV, the simian form of HIV. The proof-of-concept study examined the combined effects of therapeutic vaccination with an adenovirus serotype 26 vector vaccine and an MVA vector vaccine (Ad26/MVA) and TLR-7 agonist stimulation in ART-suppressed, SIV-infected monkeys. Findings were published online today in Nature. The study was a collaboration led by the Beth Israel Deaconess Medical Center (BIDMC) and the U.S. Military HIV Research Program (MHRP) of the Walter Reed Army Institute of Research (WRAIR), and includes scientists from Janssen Vaccines & Prevention B.V., one of the Janssen Pharmaceutical Companies of Johnson & Johnson, and Gilead Sciences, Inc. All rhesus monkeys were started on suppressive ART seven days after infection with SIV. After 24 weeks, groups of animals then either received a placebo treatment, Ad26/MVA, TLR7 agonist or a combination intervention of Ad26/MVA and TLR-7. TLR7 agonist. At 72 weeks, ART was discontinued to test the ability of the investigational therapies to affect continued virological control. "We found the combination of Ad26/MVA vaccination and TLR7 stimulation proved more effective than either component alone," said Col. Nelson Michael, Director of MHRP, who helped design the preclinical study. "This was especially striking for viral load set-point, which impacts future disease." In the combination group, the mean viral load set-point was reduced by 100 fold in all animals. Researchers saw a 2.5-fold delay of viral rebound as compared with the other groups. TLR-7Stimulation of TLR7 alone did not impact viral load or rebound. The vaccine alone reduced viral load set-point by 10 fold and only marginally delayed rebound. Though all monkeys eventually experienced viral rebound following ART interruption, three of the monkeys in the combination intervention group showed effective virologic control to undetectable viral loads following ART discontinuation. "Current antiretroviral drugs, although they're lifesaving, do not cure HIV. They merely hold it in check. We are trying to develop strategies to achieve ART-free, long-term viral suppression," said senior author Dan Barouch, MD, PhD, Director of the Center for Virology and Vaccine Research at BIDMC and Professor of Medicine at Harvard Medical School. "We reasoned that if we can activate the immune cells that might harbor the virus, then the vaccine-induced immune responses might perform better seeking them out and destroying them." A critical barrier to HIV cure is the viral reservoir that remains hidden and infects cells throughout the body, leading to viral rebound in the vast majority of HIV-infected individuals after they discontinue ART. According to Dr. Merlin Robb, Deputy Director for Clinical Research at MHRP, "the combination of Ad26/MVA vaccination and TLR7 stimulation resulted in decreased levels of viral DNA in both lymph nodes and peripheral blood. With further optimization this combination strategy may show promise to achieve a functional cure for HIV." Additionally, cellular immune breadth correlated inversely with set-point viral loads and correlated directly with time to viral rebound. According to Michael, "This gives us an immunologic correlate which can potentially be used to predict responses in humans, but this needs to be confirmed in human clinical studies." Ad26/MVA is a prime boost vaccine regimen. MHRP, in collaboration with Janssen, recently began evaluating this regimen as a therapeutic vaccine in HIV infected adults who initiated ART during acute HIV infection. That study is being conducted at the Thai Red Cross in Bangkok, and the protocol chair is Dr. Jintanat Ananworanich, MHRP's Associate Director for Therapeutics. The Ad26 vaccine was developed in partnership between the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), BIDMC and Janssen. MHRP developed the MVA vaccine in collaboration with the Laboratory of Viral Diseases at NIAID/NIH. The TLR7 agonist (GS-986) was developed by Gilead. Funding for the study was provided by the U.S. Army Medical Research and Materiel Command and the Military HIV Research Program, Walter Reed Army Institute of Research through its cooperative agreement with the Henry M. Jackson Foundation (W81XWH-11-2-0174); NIH (AI096040, AI124377, AI126603); the Ragon Institute of MGH, MIT, and Harvard. About the Walter Reed Army Institute of Research Headquartered in Silver Spring, Maryland, the Walter Reed Army Institute of Research (WRAIR) is the oldest and most diverse biomedical research laboratory in the Department of Defense. WRAIR provides unique research capabilities and innovative solutions to a range of force health and readiness challenges currently facing U.S. Service Members, along with threats anticipated during future operations. With comprehensive research units in Africa, Asia, and the Caucasus region, WRAIR is comprised of two Centers of Excellence, the Center for Infectious Disease Research and the Center for Military Psychiatry and Neuroscience.


News Article | November 10, 2016
Site: www.eurekalert.org

BOSTON - A study led by researchers at Beth Israel Deaconess Medical Center (BIDMC), in collaboration with scientists at Walter Reed Army Institute of Research (WRAIR), Janssen Vaccines & Prevention B.V., one of the Janssen Pharmaceutical Companies of Johnson & Johnson and Gilead Sciences, Inc., has demonstrated that combining an experimental vaccine with an innate immune stimulant may help lead to viral remission in people living with HIV. In animal trials, the combination decreased levels of viral DNA in peripheral blood and lymph nodes, and improved viral suppression and delayed viral rebound following discontinuation of anti-retroviral therapy (ART). The research team's findings appeared online today in the journal Nature. "The objective of our study was to identify a functional cure for HIV - not to eradicate the virus, but to control it without the need for ART," said lead author Dan Barouch, MD, PhD, Director of the Center for Virology and Vaccine Research at BIDMC. "Current antiretroviral drugs, although they're lifesaving, do not cure HIV. They merely hold it in check. We are trying to develop strategies to achieve ART-free, long-term viral suppression." Typically, vaccines "teach" the body to rid itself of viral invaders by provoking an immune response. However, HIV attacks cells of the immune system. The virus kills the majority of infected immune cells but goes dormant in others. This reservoir of dormant, infected cells, where researchers believe HIV remains hidden during antiretroviral therapy, is the primary reason HIV cannot currently be cured. Barouch and colleagues are working on strategies to draw the virus out of hiding with the goal of eradicating it from the body. "We reasoned that if we can activate the immune cells that might harbor the virus, then the vaccine-induced immune responses might perform better seeking them out and destroying them," said Barouch, who is also a Professor of Medicine at Harvard Medical School. "Indeed, we saw the best results when we combined the vaccine together with the innate immune stimulant." In the two-year long study, researchers monitored the viral loads of 36 rhesus monkeys infected with simian immunodeficiency virus (SIV), a virus similar to HIV that infects non-human primates. After taking suppressive ART drugs for six months, the monkeys were given either the experimental vaccines - an adenovirus serotype 26 vector vaccine and an MVA vector vaccine (Ad26/MVA) - alone, the immune stimulant (an experimental drug that works on a protein of the immune system called TLR-7) alone, or the Ad26/MVA and stimulant combination. A control group received no active treatment. "We found the combination of Ad26/MVA vaccination and TLR7 stimulation proved more effective than either component alone," said Col. Nelson Michael, director of MHRP, who helped design the preclinical study. "This was especially striking in viral load set-point, which impacts the future course of the disease." The experimental vaccine induced a robust immune response, both in magnitude (the number of immune cells generated) and breadth (the number of places on the virus the vaccine can targets). To evaluate the efficacy of the vaccine and the immune stimulant, the researchers discontinued ART in all animals and continued to monitor their viral loads. Animals that received only the vaccine demonstrated some reduction of viral load, but the animals that were given the vaccine/immune stimulant combination showed a reduction in plasma viral RNA levels as well as a 2.5-fold delay of viral rebound compared to controls. All nine animals showed decreased viral loads, and the virus was undetectable in a third of the animals. "If all the animals' viral loads had been undetectable, that would have been a home run," said Barouch. "But the fact that all animals showed a reduction in viral load and three out of nine were undetectable, that's a solid base hit. It's definitely something that we can work from." Study coauthors include Erica Borducchi, Crystal Cabral, Kathryn E. Stephenson, Jinyan Liu, Peter Abbink, David Ng'ang'a, Joseph P. Nkolola, Amanda L. Brinkman, Lauren Peter, Benjamin C. Lee, Jessica Jimenez, David Jetton, Jade Modesir, Shanell Mojta, Abishek Chandrashekar and Katherine Molloy all of BIDMC; Galit Alter of the Ragon Institute of MGH, MIT, and Harvard; Jeff M. Gerold and Alison L. Hill of the Program for Evolutionary Dynamics at Harvard University; Mark G. Lewis, of Bioqual; Maria G. Pau, Hanneke Schuitemaker of Janssen Infectious Diseases and Vaccines; Joseph Hesselgesser and Romas Geleziunas of Gilead Sciences; Jerome H. Kim, Merlin L. Robb and Nelson L. Michael of the U.S. Military HIV Reseach Program, Walter Reed Army Institute of Research. This work was supported by the U.S. Army Medical Research and Material Command and the Military HIV Research Program, Walter Reed Army Institute of Research through its cooperative agreement with the Henry M. Jackson Foundation (W81XWH-11-2-0174). Funding was also provided by the National Institutes of Health (AI096040, AI124377, AI1266030) and the Ragon Institute of MGH, MIT, and Harvard. Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www. .


News Article | November 7, 2016
Site: www.eurekalert.org

SILVER SPRING, Md. - The Walter Reed Army Institute of Research (WRAIR) began vaccinations today in a Phase 1 human clinical trial to test the safety and immunogenicity of the Zika purified inactivated virus (ZPIV) vaccine. Seventy-five healthy adults will be recruited to participate in the trial at WRAIR's Clinical Trial Center in Silver Spring, Md. Given the concerns for immune enhancement with other similar flaviviruses, like yellow fever and Japanese encephalitis, ZPIV will be tested in some volunteers who will first be vaccinated against one of these other flaviviruses. This is of particular military relevance, as service members are often vaccinated against these diseases and then deployed to areas where Zika is increasingly becoming endemic. WRAIR scientists developed the ZPIV vaccine candidate earlier this year. The inactivated flavivirus vaccine platform was the same technology the Institute used to create its Japanese encephalitis vaccine, which was licensed in 2009. An earlier preclinical study found that rhesus monkeys that were vaccinated with ZPIV developed a strong immune response and were protected against two strains of Zika virus. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), helped identify the viral strain used in the ZPIV vaccine, supported the preclinical safety testing, and is sponsoring the conduct of this trial. WRAIR, NIAID, and the Biomedical Advanced Research and Development Authority (BARDA) have established a joint research collaboration agreement to support the development of this vaccine. In addition to concerns about infection during deployment and travel, most military installations in the continental U.S. are concentrated in the southern states, where climate conditions and mosquito populations are favorable for Zika transmission. Col. Nelson Michael, director of WRAIR's Military HIV Research Program (MHRP) and Zika program co-lead noted that, "The Army has moved efficiently from recognizing Zika virus as a threat, producing ZPIV for use in animals and demonstrating its effectiveness in mice and monkeys, producing ZPIV for human testing, and now initiating clinical trials to establish its safety and build the case for subsequent efficacy trials. All of this was done in 10 months." This study is part of the U.S. Department of Defense response to the ongoing outbreak of Zika virus in North and South America and Southeast Asia. As of November 2, there were 149 confirmed cases of Zika virus within the military health system, including four pregnant service members and one pregnant family member. "Asymptomatic Zika infections can lead to severe birth defects and neurological complications. A safe and effective Zika vaccine that prevents infection in those at risk is a global public health priority," said Maj. Leyi Lin, principal investigator of the study. The Pilot Bioproduction Facility at WRAIR manufactured the ZPIV vaccine being used in Phase 1 clinical studies, and the Army recently signed a cooperative research and development agreement to transfer the ZPIV technology to Sanofi Pasteur to explore larger scale manufacturing and advanced development. BARDA recently awarded a six-year contract to Sanofi Pasteur to further develop this vaccine to licensure. "The Army was able to move so quickly in developing, manufacturing and testing a Zika vaccine because of its extensive experience with this vaccine platform and long standing investments in the understanding and mitigation of flaviviruses, like yellow fever, dating back to the founding of WRAIR," said Dr. Kayvon Modjarrad, Zika program co-lead and associate director for Emerging Infectious Disease Threats at WRAIR's MHRP. WRAIR's ZPIV candidate will also be included as a part of a NIH trial that began in August. That study will test ZPIV in a group of people who first receive the DNA vaccine and then are boosted with the ZPIV vaccine. Three additional Phase 1 trials using ZPIV are scheduled to begin this year: The WRAIR trial that began today is sponsored by NIAID and funded by the Departments of the Army and Defense. About the Walter Reed Army Institute of Research Headquartered in Silver Spring, Maryland, the Walter Reed Army Institute of Research (WRAIR) is the oldest and most mission diverse biomedical research laboratory in the Department of Defense. WRAIR provides unique research capabilities and innovative solutions to a range of force health and readiness challenges currently facing U.S. Service Members, along with threats anticipated during future operations. With comprehensive research units in Africa, Asia, and the Caucasus region, WRAIR is comprised of two Centers of Excellence, the Center for Infectious Disease Research and the Center for Military Psychiatry and Neuroscience.


News Article | November 9, 2016
Site: www.biosciencetechnology.com

On Monday scientists began a Phase 1 human clinical trial to test safety and immunogenicity, or the ability to provoke an immune response, of the Zika purified inactivated virus (ZPIV) vaccine. The study, supported by the National Institutes of Health’s National Institute of Allergy and Infectious Disease will vaccinate 75 healthy adults. Zika is a flavivirus that is transmitted primarily by the Ades mosquitos and causes rashes and mild fevers in adults.  It has also been linked to birth defects such as microcephaly. Scientists from the Walter Reed Army Institute of Research will first vaccinate some volunteers against other similar flaviviruses, such as yellow fever, before administering the ZPIV vaccine. Preclinical studies showed that ZPIV was successful in protecting rhesus monkeys against two strains of the Zika virus. “The Army has moved efficiently from recognizing Zika virus as a threat, producing ZPIV for use in animals and demonstrating its effectiveness in mice and monkeys, producing ZPIV for human testing, and now initiating clinical trials to establish its safety and built the case for subsequent efficacy trials,” Col. Nelson Michael, director of WRAIR’s Military HIV Research Program and Zika program co-lead said in a prepared statement. “All of this was done in 10 months.” The new vaccine candidate was established at the beginning of 2016 using the same technology used to develop the Japanese encephalitis vaccine. Sanofi Pasteur recently entered into a cooperative research and development agreement with the Army to obtain the ZPIV technology so that it can invest in larger scale manufacturing and to further develop the vaccine. The Army is invested in this research not only because troops are deployed to areas where Zika virus is a cause for concern, but also because many members of the military are concentrated in U.S. southern states where Zika transmission is more common. According to a news release, since the beginning of November there were 149 confirmed Zika virus cases in the military health system. Principal investigator of the study, Maj. Leyi Lin said that Zika infections can lead to severe birth defects and neurological issues and that a proven Zika vaccine is a global public health priority. In addition to the current study, three other Phase 1 trials will test ZPIV this year.  Scientists from St. Louis University will investigate ideal dosing to be used in further studies, while researchers from Harvard Medical School and Beth Israel Deaconess Medical Center will examine the immune response and safety of a compressed vaccine schedule. There will also be a trial to test ZPIV’s immunogenicity and safety in patients who have already been infected with the Zika virus.


News Article | November 7, 2016
Site: www.eurekalert.org

The first of five early stage clinical trials to test the safety and ability of an investigational Zika vaccine candidate called the Zika Purified Inactivated Virus (ZPIV) vaccine to generate an immune system response has begun at the Walter Reed Army Institute of Research (WRAIR) Clinical Trial Center in Silver Spring, Maryland. Scientists with WRAIR, part of the U.S. Department of Defense (DoD), developed the vaccine. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), is co-funding the Phase 1 clinical trial with WRAIR, serving as the regulatory sponsor and providing other support. The experimental ZPIV vaccine is based on the same technology WRAIR used in 2009 to successfully develop a vaccine for another flavivirus called Japanese encephalitis. The ZPIV vaccine contains whole Zika virus particles that have been inactivated, meaning that the virus cannot replicate and cause disease in humans. However, the protein shell of the inactivated virus remains intact so it can be recognized by the immune system and evoke an immune response. NIAID partially supported the preclinical development of the ZPIV vaccine candidate, including safety testing and non-human primate studies that found that the vaccine induced antibodies that neutralized the virus and protected the animals from disease when they were challenged with Zika virus. WRAIR, NIAID and the Biomedical Advanced Research and Development Authority (BARDA) part of the HHS Office of the Assistant Secretary for Preparedness and Response (ASPR) have established a joint Research Collaboration Agreement to support the development of this vaccine. "We urgently need a safe and effective vaccine to protect people from Zika virus infection as the virus continues to spread and cause serious public health consequences, particularly for pregnant women and their babies," said NIAID Director Anthony S. Fauci, M.D. "We are pleased to be part of the collaborative effort to advance this promising candidate vaccine into clinical trials." Led by WRAIR principal investigator Maj. Leyi Lin, M.D., the new study aims to enroll 75 people ages 18 to 49 years with no prior flavivirus infection. Flaviviruses include Zika virus, yellow fever virus, dengue virus, Japanese encephalitis virus and West Nile virus. Participants will be randomly divided into three groups: the first group (25 participants) will receive two intramuscular injections of the ZPIV test vaccine or a placebo (saline) 28 days apart; the other two groups (25 participants each) will receive a two-dose regimen of a Japanese encephalitis virus vaccine or one dose of a yellow fever vaccine before beginning the two-dose ZPIV vaccine regimen. Investigators chose to administer additional flavivirus vaccines because U.S. service members are often vaccinated against these diseases before deploying to Zika-endemic areas. Additionally, a subgroup of 30 of the participants who receive the two-dose ZPIV regimen will receive a third dose one year later. All participants in the trial will receive the same ZPIV dose at each injection (5 micrograms). A DoD Research Monitor, an independent physician not associated with the protocol, will monitor the conduct of the trial and report any safety issues to the WRAIR Institutional Review Board. Another independent group, the Safety Monitoring Committee, will also monitor participant safety, review data and report any issues to NIAID. As the regulatory sponsor, NIAID ensures the trial follows the study protocol and informs the FDA of any significant adverse events or risks. NIAID also maintains the Investigational New Drug (IND) application for the candidate vaccine. The WRAIR study is expected to be completed by fall 2018. Four additional Phase 1 studies to evaluate the ZPIV investigational vaccine are expected to launch in the coming months. These include BARDA is funding the advanced development of the ZPIV vaccine candidate through a six-year contract with Sanofi Pasteur, which established a collaborative research and development agreement with WRAIR to accelerate further development of the vaccine. NIAID conducts and supports research--at NIH, throughout the United States, and worldwide--to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website. About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www. .


SANTA MONICA, Calif., Oct. 28, 2016 (GLOBE NEWSWIRE) -- Opiant Pharmaceuticals, Inc. (“Opiant”) (OTCQB:OPNT), a specialty pharmaceutical company developing pharmacological treatments for substance use, addictive and eating disorders, announced that it has obtained exclusive development and commercialization rights to the heroin vaccine invented by scientists at the Walter Reed Army Institute of Research (WRAIR) and the National Institute on Drug Abuse (NIDA), a division of the National Institutes of Health (NIH).   “Aggressively addressing heroin addiction is part of Opiant’s mission,” said Roger Crystal, M.D., Chief Executive Officer of Opiant. “In our view, this vaccine fits our plan to develop innovative treatments for this condition. The vaccine has promising preclinical data.” Scientists at NIDA in Rockville, Maryland, and at WRAIR in Silver Spring, Maryland, developed a vaccine candidate that induces antibodies that then bind to heroin in the bloodstream, thereby preventing the drug from crossing the blood-brain barrier and blocking the euphoria and addictive effects. Because heroin is too small a molecule to induce antibodies on its own, the researchers worked closely with organic chemists to join the heroin analog to a carrier protein to improve its immune-inducing effect. The preclinical research was funded by NIDA. WRAIR also leveraged its expertise in novel adjuvants research to increase the immune response of the vaccine. If further pre-clinical testing is successful, Opiant plans to work with researchers at the U.S. Military HIV Research Program at WRAIR to eventually combine the heroin vaccine with their HIV vaccine candidate. “This innovative dual-vaccine model would concurrently address the entwined epidemics of heroin abuse and HIV, and could provide considerable public health benefit,” said Gary Matyas, Ph.D., the WRAIR principal investigator. “With the heroin epidemic reaching astonishing levels, we are driven at Opiant to develop new treatments for this addiction,” said Dr. Crystal. “We look forward to completing the preclinical work conducted by WRAIR and advancing into the clinic. Whilst our development of NARCAN® Nasal Spray to reverse opioid overdose has been a significant effort to address the unfortunate consequences of heroin addiction, we see the vaccine as having potential in addressing the disease itself.” Opiant Pharmaceuticals, Inc., is a specialty pharmaceutical company developing pharmacological treatments for substance use, addictive and eating disorders. Over 45 million people in the U.S. have one of these disorders. The National Institute on Drug Abuse (NIDA), a division of the National Institutes of Health (NIH), describes these disorders as chronic relapsing brain diseases which burden society at both the individual and community levels. With its innovative opioid antagonist nasal delivery technology, Opiant is positioned to become a leader in these treatment markets. Its first product, NARCAN® Nasal Spray, is marketed in the U.S. by the company’s partner, Adapt Pharma Limited. Currently, Opiant is developing opioid antagonists for the treatment of substance use, addictive and eating disorders, with a near term focus on eating disorders and cocaine use disorder. For more information please visit: www.opiant.com. This press release contains forward-looking statements. These statements relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our or our industry’s actual results, levels of activity, performance or achievements to be materially different from any future results, levels of activity, performance or achievements expressed, implied or inferred by these forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “may,” “will,” “should,” “could,” “would,” “expects,” “plans,” “intends,” “anticipates,” “believes,” “estimates,” “predicts,” “projects,” “potential,” or “continue” or the negative of such terms and other comparable terminology. These statements are only predictions based on our current expectations and projections about future events. You should not place undue reliance on these statements. Actual events or results may differ materially. In evaluating these statements, you should specifically consider various factors. These and other factors may cause our actual results to differ materially from any forward-looking statement. We undertake no obligation to update any of the forward-looking statements after the date of this press release to conform those statements to reflect the occurrence of unanticipated events, except as required by applicable law.


News Article | November 10, 2016
Site: www.sciencedaily.com

A study led by researchers at Beth Israel Deaconess Medical Center (BIDMC), in collaboration with scientists at Walter Reed Army Institute of Research (WRAIR), Janssen Vaccines & Prevention B.V., one of the Janssen Pharmaceutical Companies of Johnson & Johnson and Gilead Sciences, Inc., has demonstrated that combining an experimental vaccine with an innate immune stimulant may help lead to viral remission in people living with HIV. In animal trials, the combination decreased levels of viral DNA in peripheral blood and lymph nodes, and improved viral suppression and delayed viral rebound following discontinuation of anti-retroviral therapy (ART). The research team's findings appeared online today in the journal Nature. "The objective of our study was to identify a functional cure for HIV -- not to eradicate the virus, but to control it without the need for ART," said lead author Dan Barouch, MD, PhD, Director of the Center for Virology and Vaccine Research at BIDMC. "Current antiretroviral drugs, although they're lifesaving, do not cure HIV. They merely hold it in check. We are trying to develop strategies to achieve ART-free, long-term viral suppression." Typically, vaccines "teach" the body to rid itself of viral invaders by provoking an immune response. However, HIV attacks cells of the immune system. The virus kills the majority of infected immune cells but goes dormant in others. This reservoir of dormant, infected cells, where researchers believe HIV remains hidden during antiretroviral therapy, is the primary reason HIV cannot currently be cured. Barouch and colleagues are working on strategies to draw the virus out of hiding with the goal of eradicating it from the body. "We reasoned that if we can activate the immune cells that might harbor the virus, then the vaccine-induced immune responses might perform better seeking them out and destroying them," said Barouch, who is also a Professor of Medicine at Harvard Medical School. "Indeed, we saw the best results when we combined the vaccine together with the innate immune stimulant." In the two-year long study, researchers monitored the viral loads of 36 rhesus monkeys infected with simian immunodeficiency virus (SIV), a virus similar to HIV that infects non-human primates. After taking suppressive ART drugs for six months, the monkeys were given either the experimental vaccines -- an adenovirus serotype 26 vector vaccine and an MVA vector vaccine (Ad26/MVA) -- alone, the immune stimulant (an experimental drug that works on a protein of the immune system called TLR-7) alone, or the Ad26/MVA and stimulant combination. A control group received no active treatment. "We found the combination of Ad26/MVA vaccination and TLR7 stimulation proved more effective than either component alone," said Col. Nelson Michael, director of MHRP, who helped design the preclinical study. "This was especially striking in viral load set-point, which impacts the future course of the disease." The experimental vaccine induced a robust immune response, both in magnitude (the number of immune cells generated) and breadth (the number of places on the virus the vaccine can targets). To evaluate the efficacy of the vaccine and the immune stimulant, the researchers discontinued ART in all animals and continued to monitor their viral loads. Animals that received only the vaccine demonstrated some reduction of viral load, but the animals that were given the vaccine/immune stimulant combination showed a reduction in plasma viral RNA levels as well as a 2.5-fold delay of viral rebound compared to controls. All nine animals showed decreased viral loads, and the virus was undetectable in a third of the animals. "If all the animals' viral loads had been undetectable, that would have been a home run," said Barouch. "But the fact that all animals showed a reduction in viral load and three out of nine were undetectable, that's a solid base hit. It's definitely something that we can work from."


Stoddard M.B.,WRAIR | Stoddard M.B.,University of Alabama at Birmingham | Pinto V.,WRAIR | Keiser P.B.,WRAIR | Zollinger W.,WRAIR
Clinical and Vaccine Immunology | Year: 2010

Bacterial endotoxin interacts with the human immune system via complex immunological pathways. The evaluation of endotoxicity is important in the development of safe vaccines and immunomodulatory therapeutics. The Limulus amebocyte lysate (LAL) assay is generally accepted by the FDA for use for the quantification of lipopolysaccharide (LPS), while the rabbit pyrogen test (RPT) is used to estimate pyrogenicity during early development and production. Other in vitro assays, such as cytokine release assays with human whole blood (WB) or peripheral blood mononuclear cells (PBMCs), have also been used and may better estimate the human immunological response to products containing novel LPS molecules. In this study, WB and PBMC interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) release assays were used to estimate the endotoxic activities of purified LPS and native outer membrane vesicle (NOMV) vaccines derived from wild-type (hexa-acylated lipid A) and genetically detoxified (penta- and tetra-acylated lipid A) group B Neisseria meningitidis. A method for quantification of the differences in endotoxicity observed in the WB and PBMC assays is elucidated. The LAL assay was shown to be relatively insensitive to lipid A variations, and the RPT was less sensitive than the cytokine release assay with WB. The IL-6 and TNF-α assays with WB but not the assays with PBMCs distinguished between vaccines containing LPS from penta- and tetra-acylated strains. The high degree of sensitivity of the WB system to LPS variations and the presumed relevance of the use of human tissues to predict toxicity in humans suggest that this assay may be particularly well suited for the safety evaluation of vaccines and therapeutics containing acylation variants of LPS. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Paranavitana C.,WRAIR | Zelazowska E.,WRAIR | Dasilva L.,U.S. Army | Pittman P.R.,U.S. Army | Nikolich M.,WRAIR
Journal of Interferon and Cytokine Research | Year: 2010

To determine whether cytokines and T-cell subsets other than Th1 cells contribute to secondary immune responses against Francisella species, we investigated production of Th17-associated cytokines IL-17 and IL-22 in a recall response to Francisella tularensis. Peripheral blood mononuclear cells (PBMCs) from volunteers previously immunized with the F. tularensis live vaccine strain (LVS) were stimulated in vitro with bacterial lysates of LVS or a nonpathogenic type A B38 strain. Gene expression analysis by real-time PCR showed that IL-17 and IL-22 transcripts were induced in immune PBMCs at a significantly higher level than in cells from nonvaccinated volunteers stimulated with LVS or B38 antigens at 24?h. In addition, we detected both cell-associated and secreted IL-22 at 24?h after stimulation and IL-17 at 72?h post-stimulation. Intracellular IL-22 and IL-17 were observed in memory CD4+ cells and less in memory CD8+ cells. These findings suggest that Th17 responses in addition to the Th1 response may play an important role in adaptive immunity against Francisella. © Mary Ann Liebert, Inc.

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