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Study of coronavirus variants predicts virus evolving to escape current vaccines

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Study of coronavirus variants predicts virus evolving to escape current vaccines

A new study of the U.K. and South Africa variants of SARS-CoV-2 predicts that current vaccines and certain monoclonal antibodies may be less effective at neutralizing these variants and that the new variants raise the specter that reinfections could be more likely.

The study was published in Nature on March 8, 2021. A preprint of the study was first posted to BioRxiv on January 26, 2021.The study’s predictions are now being borne out with the first reported results of the Novavax vaccine, says the study’s lead author David Ho, MD. The company reported on Jan. 28 that the vaccine was nearly 90% effective in the company’s U.K. trial, but only 49.4% effective in its South Africa trial, where most cases of COVID-19 are caused by the B.1.351 variant.”Our study and the new clinical trial data show that the virus is traveling in a direction that is causing it to escape from our current vaccines and therapies that are directed against the viral spike,” says Ho, the director of the Aaron Diamond AIDS Research Center and the Clyde’56 and Helen Wu Professor of Medicine at Columbia University Vagelos College of Physicians and Surgeons.””If the rampant spread of the virus continues and more critical mutations accumulate, then we may be condemned to chasing after the evolving SARS-CoV-2 continually, as we have long done for influenza virus,” Ho says. “Such considerations require that we stop virus transmission as quickly as is feasible, by redoubling our mitigation measures and by expediting vaccine rollout.”

After vaccination, the immune system responds and makes antibodies that can neutralize the virus.Ho and his team found that antibodies in blood samples taken from people inoculated with the Moderna or Pfizer vaccine were less effective at neutralizing the two variants, B.1.1.7, which emerged last September in England, and B.1.351, which emerged from South Africa in late 2020. Against the U.K. variant, neutralization dropped by roughly 2-fold, but against the South Africa variant, neutralization dropped by 6.5- to 8.5-fold.

“The approximately 2-fold loss of neutralizing activity against the U.K. variant is unlikely to have an adverse impact due to the large ‘cushion’ of residual neutralizing antibody activity,” Ho says, “and we see that reflected in the Novavax results where the vaccine was 85.6% effective against the U.K. variant.”

Data from Ho’s study about the loss in neutralizing activity against the South Africa variant are more worrisome.

“”The drop in neutralizing activity against the South Africa variant is appreciable, and we’re now seeing, based on the Novavax results, that this is causing a reduction in protective efficacy,” Ho says.

The new study did not examine the more recent variant found in Brazil (B.1.1.28) but given the similar spike mutations between the Brazil and South Africa variants, Ho says the Brazil variant should behave similarly to the South Africa variant.


“We have to stop the virus from replicating and that means rolling out vaccine faster and sticking to our mitigation measures like masking and physical distancing. Stopping the spread of the virus will stop the development of further mutations,” Ho says.

The study also found that certain monoclonal antibodies used now to treat COVID patients may not work against the South Africa variant. And based on results with plasma from COVID patients who were infected earlier in the pandemic, the B.1.351 variant from South Africa has the potential to cause reinfection.

New study contains comprehensive analysis of variants

The new study conducted an extensive analysis of mutations in the two SARS-CoV-2 variants compared to other recent studies, which have reported similar findings.

The new study examined all mutations in the spike protein of the two variants. (Vaccines and monoclonal antibody treatments work by recognizing the SARS-CoV-2 spike protein.)

The researchers created SARS-CoV-2 pseudoviruses (viruses that produce the coronavirus spike protein but cannot cause infection) with the eight mutations found in the U.K. variant and the nine mutations found in the South African variant.

They then measured the sensitivity of these pseudoviruses to monoclonal antibodies developed to treat COVID patients, convalescent serum from patients who were infected earlier in the pandemic, and serum from patients who have been vaccinated with the Moderna or Pfizer vaccine.

Implications for monoclonal antibody treatments

The study measured the neutralizing activity of 18 different monoclonal antibodies — including the antibodies in two products authorized for use in the United States.

Against the U.K. variant, most antibodies were still potent, although the neutralizing activity of two antibodies in development was modestly impaired.

Against the South Africa variant, however, the neutralizing activity of four antibodies was completely or markedly abolished. Those antibodies include bamlanivimab (LY-CoV555, approved for use in the United States) that was completely inactive against the South Africa variant, and casirivimab, one of the two antibodies in an approved antibody cocktail (REGN-COV) that was 58-fold less effective at neutralizing the South Africa variant compared to the original virus. The second antibody in the cocktail, imdevimab, retained its neutralizing ability, as did the complete cocktail.

“Decisions of the use of these treatments will depend heavily on the local prevalence of the South Africa and Brazil variants,” Ho says, “highlighting the importance of viral genomic surveillance and proactive development of next-generation antibody therapeutics.”

Reinfection implications

Serum from most patients who had recovered from COVID earlier in the pandemic had 11-fold less neutralizing activity against the South Africa variant and 4-fold less neutralizing activity against the U.K. variant.

“The concern here is that reinfection might be more likely if one is confronted with these variants, particularly the South Africa one,” Ho says.

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Researchers create artificial cells that act like living cells

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Study of coronavirus variants predicts virus evolving to escape current vaccines


In a new study published in Nature Chemistry, UNC-Chapel Hill researcher Ronit Freeman and her colleagues describe the steps they took to manipulate DNA and proteins — essential building blocks of life — to create cells that look and act like cells from the body. This accomplishment, a first in the field, has implications for efforts in regenerative medicine, drug delivery systems, and diagnostic tools.

“With this discovery, we can think of engineering fabrics or tissues that can be sensitive to changes in their environment and behave in dynamic ways,” says Freeman, whose lab is in the Applied Physical Sciences Department of the UNC College of Arts and Sciences.

Cells and tissues are made of proteins that come together to perform tasks and make structures. Proteins are essential for forming the framework of a cell, called the cytoskeleton. Without it, cells wouldn’t be able to function. The cytoskeleton allows cells to be flexible, both in shape and in response to their environment.

Without using natural proteins, the Freeman Lab built cells with functional cytoskeletons that can change shape and react to their surroundings. To do this, they used a new programmable peptide-DNA technology that directs peptides, the building blocks of proteins, and repurposed genetic material to work together to form a cytoskeleton.

“DNA does not normally appear in a cytoskeleton,” Freeman says. “We reprogrammed sequences of DNA so that it acts as an architectural material, binding the peptides together. Once this programmed material was placed in a droplet of water, the structures took shape.”

The ability to program DNA in this way means scientists can create cells to serve specific functions and even fine-tune a cell’s response to external stressors. While living cells are more complex than the synthetic ones created by the Freeman Lab, they are also more unpredictable and more susceptible to hostile environments, like severe temperatures.

“The synthetic cells were stable even at 122 degrees Fahrenheit, opening up the possibility of manufacturing cells with extraordinary capabilities in environments normally unsuitable to human life,” Freeman says.

Instead of creating materials that are made to last, Freeman says their materials are made to task — perform a specific function and then modify themselves to serve a new function. Their application can be customized by adding different peptide or DNA designs to program cells in materials like fabrics or tissues. These new materials can integrate with other synthetic cell technologies, all with potential applications that could revolutionize fields like biotechnology and medicine.

“This research helps us understand what makes life,” Freeman says. “This synthetic cell technology will not just enable us to reproduce what nature does, but also make materials that surpass biology.”



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This alloy is kinky

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Study of coronavirus variants predicts virus evolving to escape current vaccines


Researchers have uncovered a remarkable metal alloy that won’t crack at extreme temperatures due to kinking, or bending, of crystals in the alloy at the atomic level.  A metal alloy composed of niobium, tantalum, titanium, and hafnium has shocked materials scientists with its impressive strength and toughness at both extremely hot and cold temperatures, a combination of properties that seemed so far to be nearly impossible to achieve. In this context, strength is defined as how much force a material can withstand before it is permanently deformed from its original shape, and toughness is its resistance to fracturing (cracking). The alloy’s resilience to bending and fracture across an enormous range of conditions could open the door for a novel class of materials for next-generation engines that can operate at higher efficiencies.

The team, led by Robert Ritchie at Lawrence Berkeley National Laboratory (Berkeley Lab) and UC Berkeley, in collaboration with the groups led by professors Diran Apelian at UC Irvine and Enrique Lavernia at Texas A&M University, discovered the alloy’s surprising properties and then figured out how they arise from interactions in the atomic structure. Their work is described in a study that was published April 11, 2024 in Science.

“The efficiency of converting heat to electricity or thrust is determined by the temperature at which fuel is burned — the hotter, the better. However, the operating temperature is limited by the structural materials which must withstand it,” said first author David Cook, a Ph.D. student in Ritchie’s lab. “We have exhausted the ability to further optimize the materials we currently use at high temperatures, and there’s a big need for novel metallic materials. That’s what this alloy shows promise in.”

The alloy in this study is from a new class of metals known as refractory high or medium entropy alloys (RHEAs/RMEAs). Most of the metals we see in commercial or industrial applications are alloys made of one main metal mixed with small quantities of other elements, but RHEAs and RMEAs are made by mixing near-equal quantities of metallic elements with very high melting temperatures, which gives them unique properties that scientists are still unraveling. Ritchie’s group has been investigating these alloys for several years because of their potential for high-temperature applications.

“Our team has done previous work on RHEAs and RMEAs and we have found that these materials are very strong, but generally possess extremely low fracture toughness, which is why we were shocked when this alloy displayed exceptionally high toughness,” said co-corresponding author Punit Kumar, a postdoctoral researcher in the group.

According to Cook, most RMEAs have a fracture toughness less than 10 MPa√m, which makes them some of the most brittle metals on record. The best cryogenic steels, specially engineered to resist fracture, are about 20 times tougher than these materials. Yet the niobium, tantalum, titanium, and hafnium (Nb45Ta25Ti15Hf15) RMEA alloy was able to beat even the cryogenic steel, clocking in at over 25 times tougher than typical RMEAs at room temperature.

But engines don’t operate at room temperature. The scientists evaluated strength and toughness at five temperatures total: -196°C (the temperature of liquid nitrogen), 25°C (room temperature), 800°C, 950°C, and 1200°C. The last temperature is about 1/5 the surface temperature of the sun.

The team found that the alloy had the highest strength in the cold and became slightly weaker as the temperature rose, but still boasted impressive figures throughout the wide range. The fracture toughness, which is calculated from how much force it takes to propagate an existing crack in a material, was high at all temperatures.

Unraveling the atomic arrangements

Almost all metallic alloys are crystalline, meaning that the atoms inside the material are arranged in repeating units. However, no crystal is perfect, they all contain defects. The most prominent defect that moves is called the dislocation, which is an unfinished plane of atoms in the crystal. When force is applied to a metal it causes many dislocations to move to accommodate the shape change. For example, when you bend a paper clip which is made of aluminum, the movement of dislocations inside the paper clip accommodates the shape change. However, the movement of dislocations becomes more difficult at lower temperatures and as a result many materials become brittle at low temperatures because dislocations cannot move. This is why the steel hull of the Titanic fractured when it hit an iceberg. Elements with high melting temperatures and their alloys take this to the extreme, with many remaining brittle up to even 800°C. However, this RMEA bucks the trend, withstanding snapping even at temperatures as low as liquid nitrogen (-196°C).

To understand what was happening inside the remarkable metal, co-investigator Andrew Minor and his team analyzed the stressed samples, alongside unbent and uncracked control samples, using four-dimensional scanning transmission electron microscopy (4D-STEM) and scanning transmission electron microscopy (STEM) at the National Center for Electron Microscopy, part of Berkeley Lab’s Molecular Foundry.

The electron microscopy data revealed that the alloy’s unusual toughness comes from an unexpected side effect of a rare defect called a kink band. Kink bands form in a crystal when an applied force causes strips of the crystal to collapse on themselves and abruptly bend. The direction in which the crystal bends in these strips increases the force that dislocations feel, causing them to move more easily. On the bulk level, this phenomenon causes the material to soften (meaning that less force has to be applied to the material as it is deformed). The team knew from past research that kink bands formed easily in RMEAs, but assumed that the softening effect would make the material less tough by making it easier for a crack to spread through the lattice. But in reality, this is not the case.

“We show, for the first time, that in the presence of a sharp crack between atoms, kink bands actually resist the propagation of a crack by distributing damage away from it, preventing fracture and leading to extraordinarily high fracture toughness,” said Cook.

The Nb45Ta25Ti15Hf15 alloy will need to undergo a lot more fundamental research and engineering testing before anything like a jet plane turbine or SpaceX rocket nozzle is made from it, said Ritchie, because mechanical engineers rightfully require a deep understanding of how their materials perform before they use them in the real world. However, this study indicates that the metal has potential to build the engines of the future.

This research was conducted by David H. Cook, Punit Kumar, Madelyn I. Payne, Calvin H. Belcher, Pedro Borges, Wenqing Wang, Flynn Walsh, Zehao Li, Arun Devaraj, Mingwei Zhang, Mark Asta, Andrew M. Minor, Enrique J. Lavernia, Diran Apelian, and Robert O. Ritchie, scientists at Berkeley Lab, UC Berkeley, Pacific Northwest National Laboratory, and UC Irvine, with funding from the Department of Energy (DOE) Office of Science. Experimental and computational analysis was conducted at the Molecular Foundry and the National Energy Research Scientific Computing Center — both are DOE Office of Science user facilities.



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Giant galactic explosion exposes galaxy pollution in action

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A team of international researchers studied galaxy NGC 4383, in the nearby Virgo cluster, revealing a gas outflow so large that it would take 20,000 years for light to travel from one side to the other.

The discovery was published today in the journal Monthly Notices of the Royal Astronomical Society.

Lead author Dr Adam Watts, from The University of Western Australia node at the International Centre for Radio Astronomy Research (ICRAR), said the outflow was the result of powerful stellar explosions in the central regions of the galaxy that could eject enormous amounts of hydrogen and heavier elements.

The mass of gas ejected is equivalent to more than 50 million Suns.

“Very little is known about the physics of outflows and their properties because outflows are very hard to detect,” Dr Watts said.

“The ejected gas is quite rich in heavy elements giving us a unique view of the complex process of mixing between hydrogen and metals in the outflowing gas.

“In this particular case, we detected oxygen, nitrogen, sulphur and many other chemical elements.”

Gas outflows are crucial to regulate how fast and for how long galaxies can keep forming stars. The gas ejected by these explosions pollutes the space between stars within a galaxy, and even between galaxies, and can float in the intergalactic medium forever.

The high-resolution map was produced with data from the MAUVE survey, co-led by ICRAR researchers Professors Barbara Catinella and Luca Cortese, who were also co-authors of the study.

The survey used the MUSE Integral Field Spectrograph on the European Southern Observatory’s Very Large Telescope, located in northern Chile.

“We designed MAUVE to investigate how physical processes such as gas outflows help stop star formation in galaxies,” Professor Catinella said.

“NGC 4383 was our first target, as we suspected something very interesting was happening, but the data exceeded all our expectations.

“We hope that in the future, MAUVE observations reveal the importance of gas outflows in the local Universe with exquisite detail.”



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