Syndicate content

Archive

May 19th, 2020

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.

Doubts Raised Over Oxford University mRNA Vaccine for COVID-19; Expert William Haseltine Says Recent Macaque Monkey Results Do Not Support Oxford’s Protection Claim

According to William Haseltine (photo), PhD, former Professor, Harvard Medical School and Harvard School of Public Health, and Founder of Human Genome Sciences, writing on May 16, 2020 in Forbes Magazine (https://www.forbes.com/sites/williamhaseltine/2020/05/16/did-the-oxford-...) “the day after data appeared from the vaccine maker Sinovac Biotech (http://www.sinovac.com/), a Beijing, China-based company, showed complete protection of rhesus macaque monkeys by their vaccine candidate (whole inactivated SARS-CoV-2 virus particles) (https://www.sciencemag.org/news/2020/04/covid-19-vaccine-protects-monkey...) (https://science.sciencemag.org/content/early/2020/05/06/science.abc1932), scientists from the Jenner Institute in Oxford issued a press release (date) announcing that their vaccine (an adenovirus vector based vaccine that carried mRNA for the SARS-CoV-2 spike protein) worked to protect rhesus monkeys and that they were moving forward with large scale human safety trials (https://www.nih.gov/news-events/news-releases/investigational-chadox1-nc...). At the time, the substantiating data was not available. Now it is, in the form of a May 13, 2020 BioRxiv preprint (https://www.biorxiv.org/content/10.1101/2020.05.13.093195v1.full.pdf) “Does the data support the claim?” Dr. Haseltine asked rhetorically in his Forbes report and his answer was “Not really.” He went on to explain, “All of the vaccinated monkeys treated with the Oxford vaccine became infected when challenged, as judged by recovery of virus genomic RNA from nasal secretions.

CytoDyn Preparing Phase 3 Protocol to Submit to FDA for Three-Arm Comparative & Combination Trial of Leronlimab and Gilead's Remdesivir

On Monday, May 18, 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 submitting a protocol to the U.S. Food and Drug Administration (FDA) for a factorial design trial to compare the effectiveness of leronlimab versus remdesivir and in combination with remdesivir for the treatment of COVID-19. Leronlimab has been administered to more than sixty patients with COVID-19 under emergency Investigational New Drug (eINDs) authorizations granted by the FDA. Preliminary results from this patient population led to CytoDyn’s Phase 2b/3 clinical trial for 390 patients, which is a randomized, placebo-controlled trial with 2:1 ratio (active drug to placebo ratio) for severe and critically ill COVID-19 population in several hospitals throughout the country. CytoDyn has also been granted a Phase 2 randomized clinical trial study in the U.S. for a Phase 2 randomized clinical trial for mild-to-moderate COVID-19 population in the U.S. CytoDyn plans to update the public regarding current eIND results later this week. “We believe the randomized head-to-head comparison of leronlimab to remdesivir, and in combination, will provide answers to the lingering question regarding effective treatment options for patients suffering from COVID-19. We look forward to working both in the United States and with potential international sites to help provide effective treatment options for COVID-19,” said Jacob Lalezari, MD, Chief Science Officer of CytoDyn. “Unfortunately, COVID-19 remains a global public health challenge, and its economic impact continues to devastate the world economy.

Moderna Announces Positive Interim Phase 1 Data for its mRNA Vaccine (mRNA-1273) Against COVID-19 Spike Protein; Phase 2 Trial in Preparation Now & Pivotal Phase 3 Trial Anticipated for July 2020

On May 18, 2020, Moderna, Inc., (Nasdaq: MRNA) (https://www.modernatx.com/) a clinical-stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, announced positive interim clinical data of mRNA-1273, its vaccine candidate against novel coronavirus (SARS-CoV-2), from the Phase 1 study led by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). Immunogenicity data are currently available for the 25-µg and 100-µg dose level (ages 18-55) after two doses (day 43) and at the 250-µg level (ages 18-55) after one dose (day 29). Dose-dependent increases in immunogenicity were seen across the three dose levels, and between prime and boost within the 25-µg and 100-µg dose levels. All participants ages 18-55 (n=15 per cohort) across all three dose levels sero-converted by day 15 after a single dose. At day 43, two weeks following the second dose, at the 25-µg dose level (n=15), levels of binding antibodies were at the levels seen in convalescent sera (blood samples from people who have recovered from COVID-19) tested in the same assay. At day 43, at the 100-µg dose level (n=10), levels of binding antibodies significantly exceeded the levels seen in convalescent sera. Samples are not yet available for remaining participants. At this time, neutralizing antibody data are available only for the first four participants in each of the 25-µg and 100-µg dose level cohorts. Consistent with the binding antibody data, mRNA-1273 vaccination elicited neutralizing antibodies in all eight of these participants, as measured by plaque reduction neutralization (PRNT) assays against live SARS-CoV-2.

May 17th

“Epigentic Memory” in Plants; Plants Are Able to “Forget” Memory of Earlier Winter So As to Still Flower at Correct Time in Following Year

A study published online on May 11, 2020 in Nature Cell Biology reveals more information on the capacity of plants, identified as “epigenetic memory,” which allows recording important information to, for example, remember prolonged cold in the winter to ensure they flower at the right time during the spring. As soon as they produce seeds, this information is "erased" from memory so they don't bloom too early the following winter. Although they do it differently than humans, plants also have memories. This so-called "epigenetic memory" occurs by modifying specialized proteins called histones, which are important for packaging and indexing DNA in the cell. One such histone modification, called H3K27me3, tends to mark genes that are turned off. In the case of flowering, cold conditions cause H3K27me3 to accumulate at genes that control flowering. The Nature Cell Biology article is titled “Targeted Reprogramming of H3k27me3 Resets Epigenetic Memory in Plant Paternal Chromatin.” Previous work, from the laboratory of Jörg Becker (https://gulbenkian.pt/ciencia/research/research-groups/plant-genomics/), PhD, Principal Investigator at the Instituto Gulbenkian de Ciência in Portugal, has shown how H3K27me3 is faithfully transmitted from cell to cell so that in the spring, plants will remember that it was cold and that winter is over, allowing them to flower at the right time. But just as importantly, once they've flowered and made seeds, the seeds need to forget this “memory” of the cold so that they do not flower too soon once winter comes around again. Because H3K27me3 is faithfully copied from cell to cell, how do plants go about forgetting this memory in seeds?

New Technology (RADICL-Seq) Reveals How RNAs, Particularly Long-Noncoding RNAs (lncRNAs), Regulate Gene Activity; RIKEN-Developed RADICL-Seq Will Allow “Deeper Understanding of the Fine Regulatory Network Governing Gene Expression”

The discovery of a huge number of long non-protein-coding RNAs (lncRNAs) in the mammalian genome was a major surprise of the recent large-scale genomics projects. An international team, led by scientists at Japan’s RIKEN Center for Integrative Medical Sciences, and including a bioinformatician from the Research Center of Biotechnology of the Russian Academy of Sciences, and the Moscow Institute of Physics and Technology (MIPT), has developed a reliable method for assessing the role of such RNAs. The new technique and the data obtained with it allow the generation of important hypotheses on how chromatin is composed and regulated, as well as identifying the specific functions of lncRNAs. Presented in an article published on February 24, 2020 in Nature Communications, the technology is called RADICL-seq and enables comprehensive mapping of each RNA, captured while interacting with all the genomic regions that it targets, where many RNAs are likely to be important for genome regulation and structure maintenance. The open-access article is titled “RADICL-Seq Identifies General and Cell Type–Specific Principles of Genome-Wide RNA-Chromatin Interactions.” It was previously believed that RNA functions mostly as an intermediary in building proteins based on a DNA template, with very rare exceptions such as ribosomal RNAs. However, with the development of genomic analysis, it turned out that not all DNA regions encode RNA, and not all transcribed RNA encodes proteins. Although the number of noncoding RNAs and those that encode proteins is about the same, the function of most noncoding RNA is still not entirely clear.