NIH launches early-stage yellow fever vaccine trial
NIH launches early-stage yellow fever vaccine trial Article taken from: https://www.nih.gov/news-events/nih-launches-early-stage-yellow-fever-vaccine-trial Image source: http://wwwnc.cdc.gov/travel/diseases/yellow-fever The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, has begun an early-stage clinical trial of an investigational vaccine designed to protect against yellow fever virus. The Phase 1 study is evaluating whether an experimental vaccine developed by the Danish biopharmaceutical company Bavarian Nordic is safe, tolerable and has the potential to prevent yellow fever virus infection. Yellow fever virus is found in tropical and subtropical areas in South America and Africa. It caused an estimated 84,000 to 170,000 severe cases of disease and 29,000 to 60,000 deaths in 2013, according to the World Health Organization (WHO). The virus is transmitted to people primarily through the bite of infected female Aedes aegypti mosquitoes. Mild cases of infection can cause fever, back pain, headache, nausea, vomiting, fatigue and weakness. Most people recover, but approximately 15 percent of those infected develop severe disease manifested as yellow eyes and skin (jaundice), hemorrhage and shock, resulting in potentially fatal kidney, liver or heart conditions. “Yellow fever has recently re-emerged as a major public health threat in parts of Africa. Although a vaccine exists to prevent this serious disease, it is currently in short supply, and it is not recommended for certain populations, such as pregnant women and people older than 60 years,” said NIAID Director Anthony S. Fauci, M.D. “We must develop new options for preventing this terrible disease.” As of July 21, 2016, the WHO has reported a total of 3,682 suspected yellow fever cases with 361 deaths in the African country of Angola. Meanwhile, another 1,798 suspected cases have been reported in the Democratic Republic of The Congo (DRC), including 85 deaths. Cases with links to Angola have also been reported in Kenya and China. More than 105 million people in Africa have been vaccinated against yellow fever in mass campaigns since 2006, according to the WHO. Despite this success, vaccine supplies are limited. In addition, in very rare cases, the current yellow fever vaccine can produce severe adverse complications, such as neurologic side effects, multiple organ system dysfunction and death. For this reason, the vaccine should not be given to infants, the elderly, pregnant women and those with compromised immune systems. Bavarian Nordic’s experimental yellow fever vaccine, dubbed MVA-BN-YF, is based on the company’s proprietary MVA-BN platform, which uses an attenuated (weakened) version of the Modified Vaccinia Ankara (MVA) virus as a vaccine vector to carry yellow fever virus genes into the body. According to Bavarian Nordic, more than 7,600 people, including 1,000 individuals who are immunocompromised, have been safely vaccinated with MVA-BN-based vaccines. The placebo-controlled, double-blinded clinical trial will enroll 90 healthy men and women ages 18 to 45 who have never been infected with a flavivirus, the family of viruses that includes yellow fever virus, West Nile virus, dengue and Zika virus, among others. Participants will be divided into six groups: One will receive the currently licensed yellow fever vaccine (15 participants) and five groups (15 participants each) will receive the investigational Bavarian Nordic vaccine, either with or without an adjuvant, a substance that is added to a vaccine to increase the body’s immune response to the vaccine. The investigational vaccine will be administered intramuscularly while the licensed yellow fever vaccine will be administered subcutaneously. Trial participants will receive one or two doses of vaccine or placebo, separated by a month. Previous laboratory and animal studies have suggested that combining MVA-BN with ISA 720, an experimental immune-boosting adjuvant that has been used in prior clinical trials, induces a strong immune response after a single dose of vaccine. One goal of the study will be to assess whether two doses of unadjuvanted vaccine or a single dose of ISA 720 adjuvanted vaccine could provide protection against yellow fever. The multi-site clinical trial will be conducted by NIAID-funded Vaccine and Treatment Evaluation Units (VTEUs) at the University of Iowa in Iowa City and Saint Louis University in Missouri. Emory Vaccine Center in Decatur, Georgia will assist in evaluating data. Source: https://www.nih.gov/news-events/nih-launches-early-stage-yellow-fever-vaccine-trial Date: July 27th. 2016
Best-selling Lipid for Skin and Hair Also Holds Promise for Alzheimer’s
Best-selling Lipid for Skin and Hair Also Holds Promise for Alzheimer’s Article taken from: http://www.biosciencetechnology.com/news/2016/07/best-selling-lipid-skin-and-hair-also-holds-promise-alzheimers Image source: http://www.biosciencetechnology.com/news/2016/07/best-selling-lipid-skin-and-hair-also-holds-promise-alzheimers The best-selling lipid in the world, often prominently featured on skin cream and shampoo labels, appears to also hold promise for Alzheimer’s treatment, scientists say. A long version of waxy, fat-like ceramide appears critical to helping brain cells called astrocytes stay focused on supporting neurons rather than contributing to their demise. Two new grants totaling about $4 million from the National Institutes of Health are helping scientists at the Medical College of Georgia at Augusta University learn more about how this good ceramide is made as opposed to a shorter version that ultimately enables the hallmark, destructive plaque of Alzheimer’s. “We want to help people avoid or a least reduce the neurodegeneration that comes with this disease,” said Dr. Erhard Bieberich, neuroscientist in the MCG Department of Neuroscience and Regenerative Medicine and principal investigator on the new grants. In this complex process, it’s actually comparatively easy for Bieberich at least to see that something is amiss, because when it is, astrocytes will lower their antenna, a solitary protrusion called a cilia, that’s centrally located on all healthy mature brain cells like a periscope on a submarine. “If you looked at a developing brain or the brain of a patient with Alzheimer’s or even cancer, the cilia would be missing because cell division is going on,” he said. “In a healthy, mature brain, you need to have sensory organelles like cilia turning growth factors off and instead finding the best position around the neuron to be nurturing,” he said. That’s how cilia also become like a flag that’s flown when the astrocyte is being helpful and lowered when it’s causing problems. “Bad astrocytes don’t have cilia; the good ones do,” he said, which brings him back to ceramide. His lab found about six years ago that cilia are, in fact, coated with the much-publicized lipid, which interacts with still unidentified proteins to mediate cilium growth. His team has since uncovered mounting evidence that bad ceramide translates to bad astrocytes because shorter ceramide cannot support the cilia. While still uncertain what determines which ceramide gets made, right now he wants to better understand just how the lipid regulates cilia on brain cells and how dysregulation leads to problems such as chronic inflammation and eventually diseases such as Alzheimer’s. He also wants to identify what he believes are the different sets of proteins long and short ceramide bind to. The ultimate goals of Bieberich and his research team include restoring production of healthy ceramide and cilia in the face of these diseases. In the healthy brain, cilia sense growth factors that keep astrocytes “quiescent,” so they don’t divide, rather do some selective traveling to tend to whatever neurons are most active at the moment. Their support is vital to healthy neurons, which don’t have a direct blood supply. So, astrocytes function like a mobile gas station that pulls up to active neurons, ensuring they get blood, glucose and other essentials. When the cilia go down, the astrocyte instead focuses on itself and dividing. “If an astrocyte is dividing, you can imagine it uses all the fuel up for itself,” Bieberich points out. In fact, astrocytes can’t divide and nourish simultaneously because the same molecular machinery necessary to make a cilium also is needed to enable cell division. “When you have a cilium, you have no division,” he said. And when you have division, these now reactive rather than quiescent astrocytes also become inflammatory, which has Bieberich wanting to know whether cilia also are important in controlling inflammation. He already knows that without their iconic antenna, these cells shed cytokines, immune cells that promote inflammation, as well as growth factors that do the same. He also already has some evidence that when inflammation is present, cilia are not. “We think by manipulating ceramide metabolism, creating the right ceramide so to speak, we can reinstall ciliogenesis,” Bieberich said. “We can convince the cell to return to the quiescent state.” The new grants will help further explore how to achieve that, including learning more about how good ceramide is made so they can figure out how to turn it on in disease states like Alzheimer’s. He already has evidence that there is plenty of bad ceramide in this disease. But all the blame doesn’t fall on misguided astrocytes. Healthy neurons don’t make much amyloid, but when they become mutated or experience metabolism problems, they can start secreting more of these essentially misfolded proteins that no longer perform their usual function and instead can hurt astrocytes and other cells. Bieberich’s team has shown that in response, astrocytes form fluid-filled vesicles to trap the amyloid, much like an efficient garbage collection system. “Healthy astrocytes don’t make vesicles. You have to dump amyloid on them, put cytokines on them, and then they make exosomes,” he said referencing the amyloid-engulfing vesicles astrocytes make to protect themselves. In fact, vesicle formation also is one of the first reactions to accompanying inflammation. Still it’s a good system that can actually protect the brain as natural garbage consumers, like macrophages, then come along to eliminate the accumulating debris. But the system also can become overwhelmed, which is how the hallmark plaque of Alzheimer’s begins to accumulate and ultimately damage and destroy neurons. Bieberich equates the scenario to an over-full landfill that simply cannot handle more waste. If he can one day enable production of more good ceramide, it should improve the now-destructive cycle so vesicles and excessive plaques don’t get made but cilia do. Source: http://www.biosciencetechnology.com/news/2016/07/best-selling-lipid-skin-and-hair-also-holds-promise-alzheimers Date: July 26th. 2016
Forms of HIV Can Cross from Chimps to Humans
Forms of HIV Can Cross from Chimps to Humans Article taken from: http://www.dddmag.com/news/2016/07/forms-hiv-can-cross-chimps-humans Image source: http://www.dddmag.com/news/2016/07/forms-hiv-can-cross-chimps-humans No one knows exactly how it happened. It may have entered through a cut or bite wound, the blood of a chimpanzee seeping into an exposed fingertip or forearm or foot. But in the early 1900s, probably near a West African rainforest, it’s thought that a hunter or vendor of bush meat – wild game that can include primates – acquired the first strain of a simian immunodeficiency virus that virologists consider the ancestor of HIV. A new study led by the University of Nebraska-Lincoln has supported this hypothesis by reporting the first in vivo evidence that strains of chimpanzee-carried SIVs can infect human cells. They include the SIV ancestor of HIV-1 M – the strain responsible for the global HIV pandemic – and another ancestral strain of HIV found only among residents of Cameroon. Yet the researchers further discovered that the SIV ancestors of two HIV strains not identified in humans also managed to invade human cells after multiple exposures in the lab. “The question was whether SIV strains that have not been found in humans have the potential to cause another HIV-like infection,” said senior author Qingsheng Li, associate professor of biological sciences and member of the Nebraska Center for Virology. “The answer is that, actually, they do. They get replicated at a very high level. It’s surprising.” Li and his colleagues came to the conclusions after inoculating mice that were implanted with human tissues and stem cells, which stimulated the growth of other cells essential to the human immune system. To explore why humans have acquired certain HIV strains while avoiding others, the team injected low doses of the four SIV strains into separate groups of the mice. The authors found that the inferred SIV forerunners of HIV-1 M and the Cameroon-specific strain required fewer opportunities to infect the mice than did the two SIV strains whose HIV descendants have not been found in humans. According to Li, this may stem from the fact that the genetic makeup of the latter two strains differs more from HIV-1 M than does the Cameroon strain, which shares more genes with its pandemic cousin. “Based on our experiments, we clearly see some differences between the strains,” said Li, whose team collaborated with the Frederick National Laboratory for Cancer Research. “That implies that there might be differences in the likelihood of cross-species transmission when a person is exposed to one strain versus another.”The team also found evidence for the long-suspected notion that SIV strains mutate upon entering cells to overcome human-specific barriers to infection. Within 14 weeks, the same viral gene in two different SIV strains – including the ancestor of HIV-1 M – regularly underwent mutations at two key positions on that gene. Li and lead author Zhe Yuan, a doctoral student in biological sciences, said the recent outbreak of the Zika virus – which remained relatively quiet for decades following its 1947 discovery in a monkey – underscores the value of pre-emptively identifying viruses that can jump from animals to humans. “The emergence and re-emergence of infectious diseases has become a constant threat to global health, social stability, safety and economic systems,” Li said. “Bill Gates recently said that nuclear war is no longer the (biggest) threat to our safety; emerging infectious diseases are. That’s probably true.” The experimental approach employed by the team could help assess the threat posed by additional SIVs and numerous other animal-carried viruses, Yuan said. This could prove especially vital given the dynamic nature of HIV and other zoonotic diseases, he said, many of which have caused new epidemics or even pandemics. “I think this analysis of the disease is very important for public health,” said Yuan, noting that a new group of HIV strains was discovered in 2009. “We want to explore this platform for evaluating new, emerging infectious diseases.” Source: http://www.dddmag.com/news/2016/07/forms-hiv-can-cross-chimps-humans Date: July 22nd. 2016
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