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May 20th, 2020

INOVIO's COVID-19 DNA Vaccine INO-4800 Demonstrates Robust Neutralizing Antibody and T Cell Immune Responses in Preclinical Models; Article Published in Nature Communications

On May 20, 2020, INOVIO (NASDAQ:INO) announced the publication of the preclinical study data for IN0-4800, its COVID-19 DNA vaccine, demonstrating robust neutralizing antibody and T cell immune responses against coronavirus SARS-CoV-2. The open-access study was published in the peer-reviewed journal Nature Communications and is titled, "Immunogenicity of a DNA Vaccine Candidate for COVID-19" and authored by INOVIO scientists and collaborators from The Wistar Institute, the University of Texas, Public Health England, Fudan University, and Advaccine. Kate Broderick (photo), PhD, INOVIO's Senior Vice President of R&D and the Team Lead for COVID-19 vaccine development, said, "These positive preclinical results from our COVID-19 DNA vaccine (INO-4800) not only highlight the potency of our DNA medicines platform, but also build on our previously reported positive Phase 1/2a data from our vaccine against the coronavirus that causes MERS, which demonstrated near-100% seroconversion and neutralization from a similarly designed vaccine INO-4700. The potent neutralizing antibody and T cell immune responses generated in multiple animal models are supportive of our currently on-going INO-4800 clinical trials." INO-4800 targets the major surface antigen Spike protein of SARS-CoV-2 virus, which causes COVID-19 disease. The studies demonstrated that vaccination with INO-4800 generated robust binding and neutralizing antibodies, as well as T cell responses in mice and guinea pigs.

Eavesdropping Crickets Drop from Sky to Evade Capture by Bats

Researchers have uncovered the highly efficient strategy used by a group of crickets to distinguish the calls of predatory bats from the incessant noises of the nocturnal jungle. The research, led by scientists at the University of Bristol (UK) and the University of Graz (Austria), and published online on May 18, 2020 in Philosophical Transactions of the Royal Society B, revealed that the crickets eavesdrop on the vocalizations of bats to help them escape their grasp when hunted. The open-access article is titled “Decision Making in the Face of a Deadly Predator: High-Amplitude Behavioural Thresholds Can Be Adaptive for Rainforest Crickets Under High Background Noise Levels.” Sword-tailed crickets (photo) of Barro Colorado Island, Panama, are quite unlike many of their nocturnal, flying-insect neighbors. Instead of employing a variety of responses to bat calls of varying amplitudes, these crickets simply stop in mid-air, effectively dive-bombing out of harm's way. The higher the bat call amplitude, the longer the crickets cease flight and farther they fall. Biologists from Bristol's School of Biological Sciences and Graz's Institute of Zoology discovered why these crickets evolved significantly higher response thresholds than other eared insects. Within the plethora of jungle sounds, it is important to distinguish possible threats. This is complicated by the cacophony of katydid (bush-cricket) calls, which are acoustically similar to bat calls and form 98 per cent of high-frequency background noise in a nocturnal rainforest. Consequently, sword-tailed crickets need to employ a reliable method to distinguish between calls of predatory bats and harmless katydids. Responding only to ultrasonic calls above a high-amplitude threshold is their solution to this evolutionary challenge.

Researchers Reveal Origins of Quarternary Hemoglobin Complex by Resurrecting Ancient Proteins; Surprisingly, Complexity Can Evolve Quickly on Evolutionary Scale

Most biological processes are carried out by complexes of multiple proteins that work together to carry out some function. How these complicated structures could have evolved is one of modern biology's great puzzles, because the proteins generally stick together using elaborate molecular interfaces, and the intermediate forms through which they came into being have been lost without a trace. Now, an international team of researchers led by University of Chicago Professor Joseph Thornton, PhD, and graduate student Arvind Pillai has revealed that complexity can evolve through surprisingly simple mechanisms. The group identified the evolutionary "missing link" through which hemoglobin--the essential four-part protein complex that transports oxygen in the blood of virtually all vertebrate animals--evolved from simple precursors. And they found that it took just two mutations more than 400 million years ago to trigger the emergence of modern hemoglobin's structure and function. The study, titled "Origin of Complexity in Haemoglobin Evolution," was published online in Nature on May 20, 2020. The research team also includes scientists at Texas A&M University, the University of Nebraska-Lincoln, and Oxford University (UK). Each hemoglobin molecule is a four-part protein complex made up of two copies each of two different proteins, but the proteins to which they are most closely related do not form complexes at all. The team's strategy, pioneered in Dr. Thornton's lab over the last two decades, was a kind of molecular time travel: use statistical and biochemical methods to reconstruct and experimentally characterize ancient proteins before, during, and after the evolution of the earliest forms of hemoglobin.

Antibody (S309) from 2003 SARS Survivor Neutralizes SARS-CoV-1 and SARS-CoV-2 by Blocking Attachment of Viral Spike Protein to Human Host Cell Receptor

An antibody first identified in a blood sample from a patient who recovered from Severe Acute Respiratory Syndrome (SARS) in 2003 inhibits related coronaviruses, including SARS-CoV-2, the cause of COVID-19, according to a new report in Nature. The antibody, called S309, is now on a fast-track development and testing path at Vir Biotechnology (https://www.vir.bio/) in the next step toward possible clinical trials. Laboratory research findings on the S309 antibody were reported online on May 18, 2020, in Nature. The article is titled: "Cross-Neutralization of SARS-CoV-2 by a Human Monoclonal SARS-CoV Antibody” (https://www.nature.com/articles/s41586-020-2349-y). The senior authors on the paper are David Veesler, PhD, Assistant Professor of Biochemistry at the University of Washington School of Medicine, and Davide Corti, PhD, Chief Scientific Officer, Humabs Biomed SA, a subsidiary of Vir Biotechnology. The lead authors are Dora Pinto and Martina Beltramello of Humabs, as well as Young-Jun Park and Lexi Walls, research scientists in the Veesler lab, which for several years has been studying the structure and function of the infection mechanisms of a variety of coronaviruses. "We still need to show that this antibody is protective in living systems, which has not yet been done," Dr. Veesler said. "Right now, there are no approved tools or licensed therapeutics proven to fight against the coronavirus that causes COVID-19," he added. If the S309 antibody is shown to work against the novel coronavirus in people, it could become part of the pandemic armamentarium. Dr. Veesler said that his lab is not the only one seeking neutralizing antibodies for COVID 19 treatment.

Using 3D-Printed Synthetic Human Lymph Nodes, Prellis Biologics Generates 300 Human Antibodies That Bind SARS-CoV-2 Virus; Company Pursuing Development of Treatment and Preventative Therapy for COVID-19 Infection

On May 19, 2020, Prellis Biologics, Inc., announced that it has generated 300 human IgG antibodies that bind to either the S1 or S2 spike protein of the SARS-CoV-2-Wuhan strain of the novel coronavirus. Using the Prellis Externalized Human Immune System™ technology, the team produced 960 synthetic human lymph nodes that were challenged with a SARS-CoV-2 vaccine-like cocktail, leading to virus-specific antibody generation. “Three hundred virus-specific IgG antibodies is a tremendous number to have at this stage. Our pipeline for class-switched antibodies has produced an order of magnitude larger pool than the typical antibody development program,” said Erin Stephens, PhD, Director of Tissue Engineering at Prellis. Prellis Biologics first built bioactive synthetic human lymph nodes in 2017, demonstrating their potential by producing human antibodies against the Zika virus. Notably, the process does not require an infected donor, extensive screening, or generation of antibodies in animals, dramatically reducing the time to produce a targeted library of candidate antibodies to less than one month. Prellis Bio recently closed a $4.3 million investment round led by Future Ventures, Khosla Ventures, and IndieBio to support the development of human anti-SARS-CoV-2 antibodies. “We funded the formation of an army of synthetic human lymph nodes to identify antibody therapies for SARS-CoV-2 and potentially all new pandemic diseases, both viral and bacterial,” said Steve Jurvetson, co-founder of Future Ventures. “It’s like having a surrogate human immune system from hundreds of people without needing to sample from infected patients, offering a rapid response procedure for any pathogen.”

May 19th

Inactivated SARS-CoV-2 Virus Effective in Immunizing Mice, Rats, and Non-Human Primates; Effective Neutralizing Antibodies Produced, Scientists from Sinovac & Other China-Based Institutions Report in Science; Immunized Macaques Resist Virus Challenge

In an article published online on May 6, 2020 in Science, researchers from Sinovac Biotech in Beijing, China, together with colleagues from other institutions in China, including the Peking Union Medical College, report the successful vaccination of mice, rats, and non-human primates (macques) with a purified, chemically-inactivated form of the SARS-CoV-2 virus (PiCoVacc). The animals all produced SARS-CoV-2-specific neutralizing antibodies. The scientists said that these antibodies neutralized ten representative SARS-CoV-2 strains. The researchers added that three immunizations, using two different doses (3 μg or 6 μg per dose), provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. The researchers stated that “these data support clinical development of SARS-CoV-2 vaccines for humans.” In conclusion, the authors wrote the following: “Although it’s still too early to define the best animal model for studying SARS-CoV-2 infections, rhesus macaques that mimic COVID-19-like symptoms after SARS-CoV-2 infection appear promising animal models for studying the disease. We provide evidences for the safety of PiCoVacc in macaques; and did not observe infection enhancement or immunopathological exacerbation in our studies. Our data also demonstrate a complete protection against SARS-CoV-2 challenge with a 6 μg per dose of PiCoVacc in macaques. Collectively, these results suggest a path forward for clinical development of SARS-CoV-2 vaccines for use in humans.

Nebraska Researchers Study Effects of Milk Exosomes on Human Gut Microbiome

Milk does a body good, as the saying goes, and Nebraska scientists are exploring how to make it even healthier by enhancing its infection-fighting properties. “We know that different parts of a person’s diet can have potential impacts on his/her microbiome, and this may influence susceptibility to infections with different gastrointestinal pathogens,” said Jennifer Auchtung (https://foodsci.unl.edu/auchtung), PhD, one of the main investigators on a new research project led by the Nebraska Center for the Prevention of Obesity-Related Diseases (NPOD) (https://cehs.unl.edu/npod/), in an April 22, 2020 news release from the University of Nebraska-Lincoln. “One of the questions we asked was whether the molecules that are found in dairy products, especially milk, can change the microbiome and influence this susceptibility to infections.” Dr. Auchtung, Assistant Professor of Food Science and Technology, is working with lead investigator Janos Zempleni (photo), PhD, Professor of Nutrition and Health Sciences, on a four-year research project, funded by a $500,000 grant from the U.S. Department of Agriculture’s National Institute of Food and Agriculture, to study how milk enhances or diminishes pathogenic bacteria. The new research builds on work Dr. Zempleni’s lab has been pursuing since 2013 to study how nutritional nanoparticles affect the human gut. “No matter what you do diet-wise, you’re always going to change the gut microbiome,” said Dr. Zempleni, NPOD’s Director and Willa Cather Professor of Molecular Nutrition. Through natural nanoparticles known as exosomes, milk delivers bioactive compounds to humans. Exosomes facilitate cell-to-cell communication through the transfer of regulatory “cargos” from donor to recipient cells.

Immune Globulin Therapy, Steroids Had Positive Outcomes in Children with Kawasaki-Like, COVID-Related Multi-System Inflammatory Syndrome in Small Study Reported in AHA’s Circulation

Treatment with antibodies purified from donated blood--immune globulin therapy--and steroids restored heart function in the majority of children with COVID-related multi-system inflammatory syndrome, according to new research published online on May 17, 2020 in an open-access article in Circulation, the flagship journal of the American Heart Association. Physicians around the world have recently noted that a small number of children exposed to COVID-19 have an emerging condition with features overlapping toxic shock syndrome and similar to a heart condition known as Kawasaki disease (https://www.heart.org/en/health-topics/kawasaki-disease), together with cardiac inflammation. The symptoms most commonly observed are high-spiking fever, unusual lethargy over several days (asthenia), digestive signs including severe abdominal pain, vomiting or diarrhea, swollen lymph nodes (adenopathy), and skin rash. In this small study, titled “Acute Heart Failure in Multisystem Inflammatory Syndrome In Children (MIS0-C) in the Context of Global SARS-CoV-2 Pandemic” (https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.048360) researchers in France and Switzerland retrospectively collected and analyzed clinical, biological, therapeutic, and early outcome data for children admitted to the pediatric intensive care unit from March 22, 2020 to April 30, 2020, with fever, cardiogenic shock, or acute left ventricular dysfunction with inflammatory state. This analysis included 35 children (ages 2 to 16; median age of 10 years). Thirty-one (88.5%) children tested positive for SARS-CoV-2 infection, and none of the children had underlying cardiovascular disease. Secondary conditions were limited, and 17% of patients were overweight (n=6).

CytoDyn and Mexico National Institutes of Health Will Participate in Collaborative Study of Leronlimab for Treatment of Severe/Critical COVID-19 Population; Study Anticipated to Consist of Approximately 30 Patients

On May 19, 2020, CytoDyn Inc. (OTC.QB: CYDY), a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced it will be coordinating with the NIH of Mexico and providing leronlimab for a trial for the severe/critical COVID-19 population in Mexico with the potential to collaborate on further CytoDyn COVID-19 trials. CytoDyn is currently enrolling a Phase 2b/3 clinical trial for 390 patients, which is a randomized, placebo-controlled with 2:1 ratio (active drug to placebo ratio). CytoDyn is also enrolling a Phase 2 randomized clinical trial with 75 patients in the mild-to-moderate COVID-19 population. CytoDyn has been granted more than 60 emergency Investigational New Drug (eIND) authorizations by the U.S. Food and Drug Administration (FDA) and plans to provide clinical updates for this patient population later in the week. “We look forward to evaluating leronlimab as a treatment option for patients of COVID-19. We have seen the devastation of this disease on the citizens of Mexico and are looking forward to providing effective treatment options to mitigate the devastation of COVID-19,” said Gustavo Reyes Terán, MD, MPH, Head of the Coordinating Commission of National Institutes of Health and High Specialty Hospitals of Mexico, an organization that coordinates the main institutions of medical care and public research in the country. Dr. Terán had earlier spent two years in San Francisco, CA, USA, completing a postdoctoral fellowship in the “Pathogenesis of HIV Disease” at the Cancer Research Institute of the University of California San Francisco (UCSF). “The NIH of Mexico is committed to help alleviate human suffering and mortality of Mexican citizens.

May 18th

Scientists ID Three FDA-Approved Drugs That Can Curb COVID-19 Virus Replication; Drugs Inhibit Key Viral Protease; One (Atovaquone) Is “Uniquely Promising,” With Reported Anti-Viral Activity Against Other RNA Viruses & Positive Effect on Lung Disease

Three drugs that are already approved by the Food and Drug Administration (FDA) or other international agencies can block the production of the novel coronavirus that causes COVID-19 in human cells, according to computational and pharmaceutical studies performed by University of Texas (UT) Southwestern scientists. These findings, published on a preprint server known as ChemRxiv (https://chemrxiv.org/articles/Identification_of_FDA_Approved_Drugs_Targe...) on May 14, 2020 prior to peer review, build on other recent research by the same UTSW team to quickly find promising agents against this often serious respiratory condition. COVID-19, caused by the SARS-CoV-2 virus, has now infected more than 4 million people and killed more than 300,000 worldwide since it emerged in December 2019. Scientists around the globe have focused their efforts on discovering potential vaccines and therapeutics to prevent and treat this disease. For example, recent studies have suggested that the anti-viral drug remdesivir shows some promise at reducing disease severity in COVID-19 patients. However, thus far, researchers have found no treatment or prophylaxis with clear evidence of clinical benefit across large populations. Developing new pharmaceuticals could take months, even with rapid approval, according to study leaders Hesham Sadek, MD, PhD, (https://profiles.utsouthwestern.edu/profile/78098/hesham-sadek.html), a Professor of Internal Medicine, Molecular Biology, and Biophysics; John W. Schoggins, PhD, (https://profiles.utsouthwestern.edu/profile/134362/john-schoggins.html), an Associate Professor of Microbiology; and Mahmoud Ahmed, PhD, (https://profiles.utsouthwestern.edu/profile/173512/mahmoud-ahmed.html), an Instructor of Internal Medicine.