Monthly Archives: January 2021

Half of Israel’s Population Will Be Vaccinated by the End of the Month

Israel‘s Health Minister Edelstein provided ministry data showing that 2,272,000 people have so far had the first of the two-shot Pfizer-BioNTech vaccine, including 550,000 who have also had their second dose. The number represents close to a quarter of Israel’s 9.3 million citizens and maintains its position as the country with the highest per capita vaccination rate in the world, according to monitoring groups.

Edelstein on Wednesday presented figures showing that over 210,000 vaccination shots were administered the day before, a new record for the country’s mass inoculation program.

Israelis recieve a Covid-19 vaccine, at a vaccination center operated by the Tel Aviv Municipality

Urging continued adherence to Health Ministry lockdown guidelines, which on Tuesday were extended until January 31, Edelstein wrote “a little more and this will be behind us.

His figures were more optimistic than numbers released by the ministry during the morning, which showed that 56,008 people had their first dose on Tuesday and another 114,769 had the second shot for a total of 170,777. It was not clear why there was a discrepancy in the numbers.

The ministry said 8,511 new cases were confirmed Tuesday, a drop of some 1,500 from the record-shattering 10,058 cases detected on Monday. The figure for Tuesday was the lowest weekday daily caseload in over a week. The positive test rate also dropped to 9.2%, having reached 10.2% on Monday.

Source: https://www.timesofisrael.com/

How Does an mRNA Vaccine Work?

The COVID-19 pandemic has brought unusual attention to everything from handwashing to polymerase chain reaction (PCR) tests. As we move into the later stages of this pandemic, though, a different scientific concept has dominated the national conversation: vaccines. The study of the human immune system and how vaccines influence it is complex and sometimes counterintuitive, and the deployment of a new method for immunization based on mRNA has made it all the more confusing.

The two vaccines that have received Emergency Use Authorizations (EUAs) from the Food and Drug Administration are both mRNA vaccines. And since they’re our only hope for ending this pandemic, it’s crucial to understand how they work—and why you should get one.

Vaccines come in a few main forms, but they share the same central goal: equip our immune systems with the tools to handily defeat a pathogen we might encounter in the future. Think of it like a practice round before your body sees the real thing.

The exact way our bodies develop this preemptive immunity depends on the kind of vaccine we’re given. Live-attenuated vaccines provide our cells with a weakened version of a pathogen; protein subunit vaccines give just one part of a bad guy, so immune cells know how to recognize that part of a virus or bacterium. But mRNA (short for messenger RNA) vaccines actually provide our cells with the instructions for making a protein from the pathogen, in essence creating their own practice dummy. Our own cells produce the viral protein specific to, say, SARS-CoV-2, and then our immune system learns to recognize the proteins.

Source: https://www.popsci.com/

Base Editing Could Cure a Host of Genetic Diseases

Picture the familiar double helix of human DNA — a long, twisted ladder with 3 billion rungs on it, each made of a pair of genetic bases (A, T, C, and G). A mistake in just one base along that ladderan A where there should be a G — can be enough to cause a disease. In fact, researchers have linked over 31,000 different mistakes, known as “point mutations,” to human diseases. Now, an advanced form of gene therapy — called base editing — could make it possible to safely correct them.

Base editing is a type of gene editing technology, just like CRISPR. However, while CRISPR cuts through both strands of the DNA ladder to swap in different genes, a base editor makes precise changes to individual letters along the genome — a much less invasive kind of DNA surgery.

It’s like your spell-checker,” neuroscientist Jeffrey Holt said. “If you type the wrong letter, spell checker fixes it for you.” Base editing was first developed by Broad Institute researcher David Liu in 2016, and it’s not perfect — the best base editors still make off-target edits and aren’t 100%  efficient. However, the technique is more efficient than CRISPR and causes fewer errors, which has made it the focus of considerable research into correcting disease-causing point mutations.

Base editing is like your spell-checker. If you type the wrong letter, it fixes it for you,” explained Jeffrey Holt. Holt was part of a team that used base editing to partially restore the hearing of mice with a point mutation that causes deafness in people. Earlier in 2020, University of Illinois researchers used base editing to slow the progression of ALS in mice. More recently, Liu was part of a group that used base editing to correct the point mutation that causes progeria, a premature-aging syndrome, in mice. By changing a T to a C in a single gene, they were able to more than double the lifespan of mice with the disease.

There’s no guarantee that a therapy that works in mice will translate to humans (although gene editing is conceptually much simpler than drugs that rely on complex chemistry). To find out whether base editing can live up to its promise as a disease-curing technology, we need human studies — and now, one is just on the horizon.

On January 12, Massachusetts-based biotech company Verve Therapeutics announced the promising results of a study testing a base editing treatment for heterozygous familial hypercholesterolemia (HeFH), a genetic heart diseaseHeFH is fairly common, affecting about one in 500 people, and it causes consistently high levels of “badcholesterol (LDL-C) — that makes people with the disease susceptible to heart attacks or strokes at a relatively young age. In primates with HeFH, Verve used base editing to change an A to a G in a single gene. Within two weeks, the animals’ blood LDL-C levels had dropped by 59%. Six months later, they were still just as low.The treatment, dubbed “VERVE-101,” was well-tolerated, with no adverse effects reported.

When we started, we had no idea this would work,” Verve CEO Sekar Kathiresan said in a press release, adding, “It works, and we expect this to be durable for the lifetime of the animals.” Now, Verve wants to find out if VERVE-101 works in humans.

Source: https://www.freethink.com/

Norway Raises Concern Over Vaccine Jabs for the Elderly

Norway expressed increasing concern about the safety of the Pfizer Inc. vaccine on elderly people with serious underlying health conditions after raising an estimate of the number who died after receiving inoculations to 29. The latest figure adds six to the number of known fatalities in Norway, and lowers the age group thought to be affected to 75 from 80. While it’s unclear exactly when the deaths occurred, Norway has given at least one dose to about 42,000 people and focused on those considered most at risk if they contract the virus, including the elderly.

There are 13 deaths that have been assessed, and we are aware of another 16 deaths that are currently being assessed,” the agency said. All the reported deaths related to “elderly people with serious basic disorders,” it said. “Most people have experienced the expected side effects of the vaccine, such as nausea and vomiting, fever, local reactions at the injection site, and worsening of their underlying condition.”

Official reports of allergic reactions have been rare as governments rush to roll out vaccines to try to contain the global pandemic. U.S. authorities reported 21 cases of severe allergic reactions from Dec. 14-23 after administration of about 1.9 million initial doses of the Pfizer vaccine. The first Europe-wide safety report on the Pfizer-BioNTech vaccine is due to be published at the end of JanuaryUntil Friday, the vaccine produced by Pfizer and BioNTech SE was the only one available in Norway, and “all deaths are thus linked to this vaccine,” the Norwegian Medicines Agency said in a written response to Bloomberg on Saturday.

Source: https://www.bloomberg.com/

Nanomicelles Are Perfect Carrier To Destroy Cancerous Cells

With the advance in nanotechnology, researchers across the globe have been exploring how to use nanoparticles for efficient drug delivery. Similar to nanoshells and nanovesicles, nanomicelles are extremely small structures and have been noted as an emerging platform in targeted therapy. Nanomicelles are globe-like structures with a hydrophilic outer shell and a hydrophobic interior. This dual property makes them a perfect carrier for delivering drug molecules.

Now a multi-disciplinary, multi-institutional team has created a nanomicelle that can be used to deliver a drug named docetaxel, which is commonly used to treat various cancers including breast, colon and lung cancer.

Modus operandi: Once injected intravenously, these nanomicelles can easily escape the circulation and enter the solid tumours.

The ideal goal for cancer therapy is destroying the cancer cells without harming healthy cells of the body, and chemotherapeutics approved for treatment of cancer are highly toxic. The currently used docetaxel is a highly hydrophobic drug, and is dissolved in a chemical mixture (polysorbate-80 and alcohol). This aggravates its toxic effects on liver, blood cells, and lungs. So, there was an urgent and unmet need to develop effective drug delivery vehicles for docetaxel without these side effects,” explains Avinash Bajaj, from the Laboratory of Nanotechnology and Chemical Biology at the Regional Centre for Biotechnology, Faridabad. He is one of the corresponding authors of the paper recently published in Angewandte Chemie.

The nanomicelles are less than 100nm in size and are stable at room temperature. Once injected intravenously these nanomicelles can easily escape the circulation and enter the solid tumours where the blood vessels are found to be leaky. These leaky blood vessels are absent in the healthy organs. “Chemical conjugation would render the phospholipid-docetaxel prodrug to be silent in the circulation and healthy organs. But once it enters the cancer cells, the enzymes will cleave the bond to activate the drug, and kill the cancer cells,” adds Dr. Bajaj.

The team tested the effectiveness of the nanomicelles in a mice breast tumour model and was found to help in tumour regression. Its toxicity was compared with the currently used FDA approved formulation and found to be less toxic. Similar promising results were seen when tested in higher model organisms including rats, rabbits and rhesus monkeys.

https://www.thehindu.com/

Immune System Killer Cells Controlled By Circadian Rhythms

An analysis of an exhaustive dataset on cells essential to the mammalian immune system shows that our ability to fight disease may rely more heavily on daily circadian cycles than previously assumed.

Malfunctions in , the process that keeps our bodies in tune with the day/night cycles, are increasingly associated with diabetes, cancer, Alzheimer’s, and many other diseases. An investigation published today in Genome Research shows that the activity of macrophagescells within us that seek and destroy intruders like bacteria—may time daily changes in their responses to pathogens and stress through the circadian control of metabolism. In this study, Jennifer Hurley, the Richard Baruch M.D. Career Development Assistant Professor of Biological Sciences at Rensselaer Polytechnic Institute and senior author on this study, and her team investigated how the levels of RNA and proteins in macrophages change over two days.

We have shown there is an incredible amount of circadian timing of macrophage behavior, but the clock is timing macrophages in unexpected ways” said Hurley.

The circadian system is comprised of a set of core clock proteins that anticipate the day/night cycle by causing daily oscillations in levels of enzymes and hormones, and ultimately affecting physiological parameters such as body temperature and the immune response. This molecular clock marks time through a self-regulating cycle of  production and decay. The “positive” element proteins of the clock trigger production of the “negative” element proteins, which in turn block production of positive element proteins until the negative element proteins decay, thus creating a negative feedback cycle that occurs once every 24 hours.

Positive element proteins also regulate fluctuations in a substantial number of gene products, known as messenger RNA or mRNA. Genetic instructions are transcribed from DNA to mRNA, which are then used as a recipe for assembling proteins, the functional building blocks of the cell. It has long been assumed that the levels of each subsequent step could be predicted from the previous. If that were the case, oscillating mRNA would correspond with oscillating levels of cellular proteins, and therefore, if one could track mRNA, they would know what proteins the circadian clock controlled in the cell.

However, this investigation showed that this paradigm may not always be true. The analysis of the macrophage dataset revealed that there was a substantial mismatch between the proteins and mRNAs that are controlled by the circadian clock. This data paralleled research published in Cell Systems in 2018 by the Hurley lab, showing that about 40% of oscillating proteins in the fungus and circadian model system, Neurospora crassa, had no corresponding oscillating mRNA.

But the scale of the difference in macrophages really surprised us,” Hurley said. “Eighty percent of the proteins that oscillate don’t have associated oscillating mRNA in macrophages. That means we were really missing how the clock was timing immunity.”

Source: https://medicalxpress.com/

New Drug Reduces Risk Of Death By 24% For Critically Ill COVID Patients

Patients across the UK who are admitted to intensive care units due to COVID-19 are set to receive new life-saving treatments which can reduce the time spent in hospital by up to 10 days, the government has announced today (Thursday 7 January).

Results from the government-funded REMAP-CAP clinical trial published today showed tocilizumab and sarilumab reduced the relative risk of death by 24%, when administered to patients within 24 hours of entering intensive care.

Most of the data came from when the drugs were administered in addition to a corticosteroid, such as dexamethasone – also discovered through government-backed research through the RECOVERY clinical trial – which is already provided as standard of care to the NHS.

Patients receiving these drugs, typically used to treat rheumatoid arthritis, left intensive care between 7 to 10 days earlier on average. The rollout of these treatments could therefore contribute significantly towards reducing pressures on hospitals over the coming weeks and months.

Source: https://www.gov.uk/

From Tobacco Plant To 100% Efficient COVID Vaccine

Under a winter’s snow cover on the outskirts of Quebec City in Canada, a high-tech greenhouse, set at a balmy 23 C, is growing row after row of a weed that could help end the coronavirus pandemicIt’s called Nicotiana benthamiana, a relative of the tobacco plant, native to Australia, and it is a key to biopharmaceutical company Medicago’s COVID-19 vaccineMedicago is the leading Canadian-based contender to produce a vaccine, with an agreement to provide the federal government with 76 million doses if approved for use.

Medicago’s vaulting onto the mainstage could provide a breakthrough for vaccine science. It involves a new technology that’s rapid and nimble, and a vaccine that can be stored at normal fridge temperatures, of 2 C to 8 C, unlike the two other vaccines currently in circulation, which each require frozen or ultra-cold frozen storage. While it’s possible the company may emerge as the new wunderkind of the Canadian biotech sector, it wasn’t without adversity. For years, Medicago warned that Canada needed to prepare itself for a pandemic and lobbied government officials for funding to build a domestic manufacturing site for a vaccine. But Medicago didn’t get what it needed from the federal government until after the COVID-19 crisis struck. On top of that, in the middle of a pandemic, Medicago is restructuring. In July, it announced plans to distance itself from a significant shareholder, Philip Morris International, which owns about one-third of the company — a controversial association with Big Tobacco that has been the source of roadblocks and criticism. Then in December, the company replaced its president and CEO. But despite this, Medicago hasn’t lost sight of its goal: a vaccine.

In phase one of its clinical trials, 100 per cent of people who received its COVID-19 vaccine developed significant antibody responses with no severe adverse effectsPhase two clinical trials are currently wrapping up and phase three is expected to begin later this month. It will involve 30,000 people in 11 countries — including Canada — and will ultimately determine if the vaccine protects people from COVID-19. The vaccine requires two doses, 21 days apart, and if approved by Health Canada, could be in the arms of Canadians by the second half of this year.

Source: https://globalnews.ca/

Alzheimer’s Is Actually 3 Distinct Disease Subtypes

Alzheimer’s Disease (AD) is probably more diverse than our traditional models suggest. Postmortem, RNA sequencing has revealed three major molecular subtypes of the disease, each of which presents differently in the brain and which holds a unique genetic risk.  Such knowledge could help us predict who is most vulnerable to each subtype, how their disease might progress and what treatments might suit them best, potentially leading to better outcomes. It could also help explain why effective treatments for AD have proved so challenging to find thus far.

The mouse models we currently have for pharmaceutical research match a particular subset of AD,  but not all subtypes simultaneouslyThis may partially explain why a vast majority of drugs that succeeded in specific mouse models do not align with generalised human trials across all AD subtypes,”  say the authors. “Therefore,” the authors conclude, “subtyping patients with AD is a critical step toward precision medicine for this devastating disease.

Traditionally, AD is thought to be marked by clumps of amyloid-beta plaques (), as well as tangles of tau proteins (NFTs) found in postmortem biopsies of the brain. Both of these markers have become synonymous with the disease, but in recent years our leading hypotheses about what they actually do to our brains have come under question. Typically, accumulations of and NFT are thought to drive neuronal and synaptic loss, predominantly within the cerebral cortex and hippocampus. Further degeneration then follows, including inflammation and degeneration of nerve cells‘ protective coating, which causes signals in our brains to slow down.

Strangely enough, however, recent evidence has shown up to a third of patients with a confirmed, clinical diagnosis have no Aβ plaques in postmortem biopsies. What’s more, many of those found with plaques at death did not show cognitive impairment in life. Instead of being an early trigger of AD, setting off neurodegeneration and driving memory loss and confusion, in some people, Aβ plaques appear to be latecomers. On the other hand, recent evidence suggests tau proteins are there from the very earliest stages.

In light of all this research, it’s highly likely there are specific subtypes of AD that we simply haven’t teased apart yet. The new research has helped unbraid three major strands. To do this, researchers analysed 1,543 transcriptomes – the genetic processes being express in the cellacross five brain regions, which were collected post mortem from two AD cohorts.

Source: https://advances.sciencemag.org/

Single Dose Nanoparticle Vaccine Efficient To Produce Covid Antibodies

Across the world, health care workers and high-risk groups are beginning to receive COVID-19 vaccines, offering hope for a return to normalcy amidst the pandemic. However, the vaccines authorized for emergency use in the U.S. require two doses to be effective, which can create problems with logistics and compliance. Now, researchers reporting in ACS Central Science have developed a nanoparticle vaccine that elicits a virus-neutralizing antibody response in mice after only a single dose.

The primary target for COVID-19 vaccines is the spike protein, which is necessary for SARS-CoV-2’s entry into cells. Both of the vaccines currently authorized in the U.S. are mRNA vaccines that cause human cells to temporarily produce the spike protein, triggering an immune response and antibody production.

Peter Kim and colleagues wanted to try a different approach: a vaccine consisting of multiple copies of the spike protein displayed on ferritin nanoparticles. Ferritin is an iron storage protein found in many organisms that self-assembles into a larger nanoparticle. Other proteins, such as viral antigens, can be fused to ferritin so that each nanoparticle displays several copies of the protein, which might cause a stronger immune response than a single copy.

The researchers spliced spike protein and ferritin DNA together and then expressed the hybrid protein in cultured mammalian cells. The ferritin self-assembled into nanoparticles, each bearing eight copies of the spike protein trimer. The team purified the spike/ferritin particles and injected them into mice. After a single immunization, mice produced neutralizing antibody titers that were at least two times higher than those in convalescent plasma from COVID-19 patients, and significantly higher than those in mice immunized with the spike protein alone. A second immunization 21 days later produced even higher antibody levels. Although these results must be confirmed in human clinical trials, they suggest that the spike/ferritin nanoparticles may be a viable strategy for single-dose vaccination against COVID-19, the researchers say.

Source: https://www.acs.org/