Category: Covid-19 Vaccine

Every week there are numerous scientific studies published. Heres a look at some of the more interesting ones.

Another COVID-19 Vaccine Looks Promising

According to the World Health Organization, there are 70 vaccines being developed worldwide for COVID-19, with three already in human clinical trials. The furthest along is one by CanSino Biologics and the Beijing Institute of Biotechnology, which is in Phase II. The others are by U.S. companies, Inovio Pharmaceuticals and Moderna. Another institution, the University of Pittsburgh, also announced that in laboratory tests their COVID-19 vaccine, delivered via a fingertip-sized patch, showed positive results in laboratory mice, producing antibodies specific to SARS-CoV-2 at enough amounts to neutralize the virus. The research was published in EBioMedicine, published by The Lancet.

We had previous experience on SARS-CoV in 2003 and MERS-COV in 2014, said co-senior author Andrea Gambotta, associate professor of surgery at the Pitt School of Medicine. These two viruses, which are closely related to SARS-CoV-2, teach us that a particular protein, called a spike protein, is important for inducing immunity against the virus. We know exactly where to fight this new virus. Thats why its important to fund vaccine research. You never know where the next pandemic will come from.

It uses a more traditional process than the mRNA one being used by Moderna. The virus is being called PittCOVacc, and uses laboratory-manufactured pieces of viral protein to build immunity. Its a process similar to that used in seasonal flu shots. They also leveraged a new technique to deliver the drug, called a microneedle array, to increase the potency of the vaccine. The fingertip-sized patch has 400 tiny needles that deliver the spike protein pieces into the skin. It goes on like a Band-Aid. The needles are built from sugars and the antigens, and they just dissolve.

We developed this to build on the original scratch method used to deliver the smallpox vaccine to the skin, but as a high-tech version that is more efficient and reproducible patient to patient, said Louis Falo, co-senior author and professor and chair of dermatology at Pitts School of Medicine and UPMC. And its actually pretty painlessit feels kind of like Velcro.

They are currently submitting an Investigational New Drug (IND) with the U.S. Food and Drug Administration (FDA) and hope to begin Phase I human clinical trials in the next few months.

Genetic Mechanisms of Inflammatory Bowel Disease

Researchers at Children's Hospital of Philadelphia identified a genetic variant that causes the development of inflammatory bowel disease (IBD). The pathway is linked to other immune disorders. More than 240 genetic regions are already associated with IBD, but each region has multiple markers and not all are causative. The researchers focused on the single nucleotide polymorphism (SNP) rs1887428, located on the promoter region of the JAK2 gene. The protein coded by the gene controls the production of blood cells. The team found that two transcription factors, RBPJ and CUX1, recognize the DNA sequence altered by the rs1887428 SNP, and while it only has mild influence on JAK2 expression, it was amplified by other proteins in the JAK2 pathway.

Possible Mechanism of Link Between Obesity and Breast Cancer

Breast cancer (and other cancers) and obesity are associated, but the reason for that link isnt well understood. Researchers from the University of Louisville published research suggesting that the fatty acid binding protein family, especially FABP4, plays a critical role. Fat tissue produces FABP4 within fat cells, which processes and distributes water-insoluble long-chain fatty acids. Normally, some FABP4 enters the bloodstream, but the higher fat volume, the more FABP4 is secreted. They believe two mechanisms are in play. Within cells, FABP4 increases in certain tumor-associated macrophages, which accumulate in tumors and promote cancer growth. And second, when elevated levels of FABP4 circulate outside the fat cells, it promotes breast cancer by directly interacting with breast cancer cells.

Using Cellular Machinery Without the Cells to Develop Drugs

Northwestern University and ShanghaiTech University leveraged cell-free synthetic biology to produce a drug that kills SARS-CoV-2 in cell cultures. They indicate they could create the new drug by taking the molecular machinery out of cells and using that machinery to make a product in a safe, cheap and quick way. The molecule is called valinomycin. By using this method, they were able to increase production yields more than 5,000 times in only a few quick design cycles.

Glucose Metabolism Linked to Alzheimers Disease

Researchers with the National Institutes of Healths National Institute on Aging conducted the largest study so far on proteins related to Alzheimers and identified proteins and biological processes that regulate glucose metabolism that are associated with Alzheimers. The study was published in the journal Nature Medicine.

The study was part of the Accelerating Medicines Partnership for Alzheimers Disease (AMP-AD). The investigators assayed the levels and analyzed the expression patterns of more than 3,000 proteins in brain and cerebrospinal fluid samples collected at centers across the U.S.

This is an example of how the collaborative, open science platform of AMP-AD is creating a pipeline of discovery for new approaches to diagnosis, treatment and prevention of Alzheimers disease, said Richard J. Hodes, NIA director. This study exemplifies how research can be accelerated when multiple research groups share their biological samples and data resources.

The study involved analyzing protein expression patterns in more than 2,000 human brain and almost 400 cerebrospinal fluid samples taken from both healthy individuals and Alzheimers patients. They analyzed how the protein modules relate to Alzheimers and other neurodegenerative diseases. They observed changes in proteins related to glucose metabolism and an anti-inflammatory response in glial cells in brain tissues from both Alzheimers patients and people with documented brain pathology who were cognitively normal. This also would seem to support increasing evidence that brain inflammation is involved in the disease as well.

In Alzheimers patients, they found that how cells extract energy from glucose is increased in both the brains and spinal fluid of Alzheimers patients. The proteins observed were also elevated in preclinical Alzheimers patients, which is to say, people with brain pathology of the disease who had not shown cognitive decline.

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Research Roundup: Another Promising COVID-19 Vaccine and More - BioSpace

I certainly dont trust the government, but neither am I credulous (see above). And its not just me. Last year, in 2019, a Pew poll found that only seventeen percent of Americans state they can trust the government just about always or most of the time, being three percent and fourteen percent, respectively. Eighty-three percent of Americans are not anti-vaccine, and to conflate government mistrust with it, thereby smearing what can be fairly termed as almost all Americans, is partisanship parading as scientific objectivity.

Originally posted here:

How the Anti-Vaccine Community Is Responding to Covid-19 - Undark Magazine

Antibodies from recovered patients and biotech companies could help

Editors note: The Economist is making some of its most important coverage of the covid-19 pandemic freely available to readers of The Economist Today, our daily newsletter. To receive it, register here. For our coronavirus tracker and more coverage, see our hub

DURING THE flu pandemic of 1918-19 doctors at an American naval hospital developed a treatment which, according to the American Journal of Public Health, had a decided influence in shortening the course of the disease and in lowering the mortality. It involved clotting and then centrifuging blood from people who had got over the disease so as to separate out the antibodies it contained, then giving those antibodies to patients in dire need.

Since then antibody-rich convalescent plasma (CP) has been used as a treatment for various diseases, including SARS and the pandemic strains of H1N1 and H5N1 influenza. Now covid-19 has joined the list. A recent study in Wuhan found that severely ill covid-19 patients treated with CP did significantly better than patients matched with them by age, gender and severity of infection had done earlier in the epidemic.

Michael Joyner of the Mayo Clinic, which leads a CP research effort in America, expects randomised control trials to begin in a few weeks. They will not just look at CPs potential as a treatment, but also as a prophylactic. If that worked, it would be a sort of halfway house on the road to a vaccine.

Even though CP donors get the other components of their bloodcells, platelets and the likereturned to them after the antibodies have been removed, the process is still something of a palaver, requiring a lot of medical attention. Despite the fact that various companies are trying to make a go of it, it is hard to see it scaling up all that far. But there is an alternative. Antibodies are proteins, and that means a bit of genetic engineering will allow cell lines at biotechnology and pharma companies to mass produce them. The resulting product should be less prone to contamination, more consistent, and easier to scale up than CP.

This approach has already been successful against Ebola. Regeneron, an American biotech company, developed a cocktail of three antibodies which recognised different parts of the proteins coat. Trials in the Democratic Republic of Congo showed this therapy to be better than remdesivir, a drug designed to block the Ebola vaccines reproduction which is now, as it happens, being tested as a medicine for covid-19.

Regeneron is now making a pair of antibodies that target the SARS-CoV-2 spike protein. It hopes to have produced enough to start trials soon. As with CP, it is possible that such antibodies may temporarily confer immunity on the uninfected, as well as helping the infected fight the disease.

Dig deeper:For our latest coverage of the covid-19 pandemic, register for The Economist Today, our daily newsletter, or visit our coronavirus tracker and story hub

This article appeared in the Briefing section of the print edition under the headline "Survivors as saviours"

Excerpt from:

Some benefits of a covid vaccine could come early - The Economist

Scientists around the world are racing to find ways out of the new coronavirus pandemic. Some are working to develop new drugs and vaccines, while others are looking to see whether therapies we already have may help against COVID-19.

In the latter category, researchers have dusted off one intriguing compound in our collective medicine cabinet a century-old vaccine to fight tuberculosis, a bacterial disease that affects the lungs. A couple of early analyses, which have yet to be peer-reviewed, have found that countries that require this vaccine, called Bacillus CalmetteGurin (BCG), seemed to have been hit less severely, in terms of both number and severity, by the coronavirus that causes the disease COVID-19.

Could this vaccine be protecting people from COVID-19? The short answer is: We don't know. But several clinical trials around the world are now examining whether this vaccine could protect against this new foe.

Related: 13 coronavirus myths busted by science

"I was originally quite skeptical" that the studies could tease apart all of the other factors that could be causing some countries to be hit harder with COVID-19 than others, said Paula Cannon, a distinguished professor of molecular microbiology and immunology at the University of Southern California's Keck School of Medicine, who is not a part of any of these studies. Among those factors are the quality of the healthcare system, measures put in place to fight the disease and testing capacity. Still, it is a "provocative idea" and the "data is tantalizing," Cannon said.

Dozens of countries, including Japan and China, require children typically newborns to receive the BCG vaccine as protection against tuberculosis, an infection that is typically more common in lower-income countries. Other countries, such as Spain, France and Switzerland, used to require the vaccine but stopped because the risk of catching the disease in those countries lessened, according to one of the preprint studies published in medRxiv on March 28. Other countries, such as the U.S., Italy and the Netherlands never had such a universal vaccine policy for the BCG vaccine.

But scientists have long known that "almost by lucky accident," the BCG vaccine doesn't just protect against tuberculosis, it also helps fight other viruses, respiratory infections in particular, Cannon said. The vaccine, "in some sort of unexpected and magical way, is like a broad immune booster," she said.

For example, one study conducted in Guinea-Bissau in West Africa found that children who were vaccinated with BCG had about a 50% reduction in overall mortality, largely because the vaccine reduced respiratory infections and sepsis, or blood poisoning, according to the medRxiv study. Other studies, mostly conducted in animals, have found similar broad-spectrum protections from the BCG vaccine.

The BCG vaccine is made up of weakened forms of live Mycobacterium bovis, closely related to the bacteria that causes tuberculosis. It was first developed in the 1920s in Paris and later shipped all over the world.

Now, countries from Japan to Denmark have their own BCG vaccines, made using different formulations of live bacteria and each one has varying degrees of immune boosting ability, said Dr. Ofer Levy, the director of the precision vaccines program at Boston Children's hospital and a professor at Harvard Medical School.

Typically, live vaccines provide a "strong and long-lasting immune response" and sometimes even "lifelong protection" against the germ, whereas inactivated forms of vaccines, such as those in flu shots don't provide immunity that's "as strong," according to the U.S. Department of Health and Human Services.

While most vaccines prompt one arm of the immune system the adaptive immune system to create antibodies that target very specific pathogens, the BCG vaccine taps into the other arm, the innate immune system. This system doesn't discriminate against pathogens and releases immune cells rather quickly to fight any foreign substance. The BCG vaccine thus boosts the body's production of non-specific immune cells.

The medRxiv study and another preliminary study recently published in Research Gate came to similar conclusions: there seemed to be a correlation between countries that require BCG vaccines and a reduced spread and severity of COVID-19 cases. For example, Portugal which has required BCG vaccines for infants has over 16,000 cases of COVID-19 but only 535 deaths whereas neighboring Spain has over 169,000 cases and over 17,000 deaths.

Similarly, Ireland, with 9,655 cases and only 334 deaths, requires the BCG vaccination, whereas the U.K. with 89,554 cases and 11,346 deaths no longer does. Based on these numbers, Ireland has a fatality rate 3.5% whereas the U.K. has a fatality rate of 12.7%. Of course, there are big population number differences across these countries, along with other variables that could affect death and infection rates.

These preliminary studies are "very flawed," because many factors such as differences in wealth and testing ability, can affect the outcomes Levy told Live Science. But the authors are "doing the best they can in a very difficult situation." While there's no direct evidence that BCG vaccines will reduce people's risk of developing COVID-19, "I'm enthusiastic about the hypotheses," Levy said.

It's difficult to draw firm conclusions, but there's enough scientific evidence to prompt clinical trials, and his team is looking into starting one in the U.S, he said. Clinical trials analyzing the protective effects of the vaccine against COVID-19 are already underway in other countries, including Australia and the Netherlands.

"I'm kind of puzzled," by the implication that the BCG vaccine might be able to protect for such a long period of time once someone has received it as a baby, Cannon said. Indeed, it's not clear how long the BCG vaccine effects can last.

The second study, which also has not been peer-reviewed, analyzed how countries with re-vaccination policies or booster shots fared in the COVID-19 pandemic. That study found that countries without re-vaccination policies had a 5.2% case fatality rate, versus a0.6% case fatality rate in countries that required re-vaccination.

"The big kind of asterisk, if you like, against all of these studies, is that they are really dealing with massively incomplete information," Cannon said. "We're all guessing what the true infection rates and the case fatality rates are because there isn't widespread uniform testing in every country."

Still, "I applaud the authors for at least, you know, doing what they could with the available data and providing some very provocative hypotheses," she said. "The good news is they're very testable."

In another world, we would be doing animal experiments to test this hypothesis. In this world, amid the coronavirus pandemic, we don't have time for that, she said. But the BCG vaccine has a "very safe track record," and likely can be tried in those who aren't old and who don't have weakened immune systems (since this is a live vaccine, it can potentially cause more side effects for older people or those with weakened immune systems), she added.

The human immune system is like an orchestra, "it's massively interconnected and what the BCG vaccine seems to do is maybe it gives like a little bit of extra control to the conductor," Cannon said. "So in the symphony of immune attack against respiratory viruses, the orchestra is able to go full blast, straightaway, all together, in sync, rather than kind of playing catch up."

Originally published on Live Science.

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Could a 100-year-old vaccine protect against COVID-19? - Livescience.com

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In GlobalDatas Coronavirus Disease (Covid-19): Pipeline and Clinical Trial Analysis April 2020 thematic report, 1,561 visitors of GlobalDatas Pharmaceutical Technology website responded to the question How confident are you that Pharma/Biotech Companies will be able to develop an effective vaccine for Covid-19 within the next 12 months? A strong majority (80%) were optimistic about the development of a vaccine, with 52% being very confident, 28% somewhat confident, and only 20% who expressed no confidence at all. However, considering that vaccines typically take years to develop, expectations surrounding the potential availability of a Covid-19 vaccine should be tempered.

Covid-19 therapeutics could be available within a matter of months, as off-the-shelf solutions may already be available and ready for clinical trials. Assuming rapid trial initiation, these trials could produce readouts in a matter of weeks. Data are already available for multiple candidate therapies, including chloroquine/hydroxychloroquine, ritonavir + lopinavir, remdesivir, and favipiravir, among others. Notably, these data have been produced less than five months after the discovery of the virus, demonstrating that short studies for Covid-19 treatments can indeed be completed quite rapidly, although the data are less clear than desired. However, it is unrealistic to expect vaccines to follow a similar timeframe for multiple reasons.

Vaccines work by training the immune system to respond to components of pathogens, and accordingly must be highly specific to the pathogen of interest. As the virus responsible for Covid-19 is new, its components are poorly understood, making it difficult to decide which parts might be more immunogenic and thus more likely to lead to a successful vaccine. While several vaccines have entered clinical trials, such as Modernas messenger ribonucleic acid (mRNA) vaccine mRNA-1273, the amount of time dedicated to the R&D of these candidates has been substantially shorter than other vaccines that have entered clinical trials. Part of the reason these vaccines were able to enter Phase I studies so quickly is because they rely on new vaccine technologies, such as DNA, mRNA, or adenoviral vector-driven vaccines, which can be developed rapidly relative to older technologies. However, no vaccine using these technologies has ever been commercialised, and data supporting their efficacy is thin. As such, enthusiasm surrounding their likelihood of success may be met with disappointment.

Prophylactic vaccines confer active immunity against a potentially disease-causing pathogen. Even if a vaccine is effective, the protection it confers must be measured against time because exposure to the pathogen could take weeks, months, or even years. This means that the endpoint for the time after immunisation needs to be longer rather than shorter in order to ensure that the pathogen is likely to have been encountered. If a trial is too short, an immunised patient might not be exposed to the disease, which could either make it difficult to differentiate the treatment from placebo or could confer a false sense of efficacy, as the rate of disease in the vaccinated group would be lower.

Even if a vaccine were to rapidly demonstrate efficacy in both Phase I and II trials, there would need to be significant manufacturing efforts initiated prior to proof of efficacy. Waiting for trial results could significantly delay the delivery of the vaccine to the public. However, increasing production prior to the release of the trial results is risky due to the possibility of failure to meet endpoints, so most developers usually avoid this option. The availability of a vaccine will likely depend heavily on the geography where it is developed and who is recommended to receive it upon licensure. For example, a Covid-19 vaccine developed in the US might initially be recommended for older patients in the US who are at increased of disease, while younger patients and those in other regions might have to wait for later releases of the vaccine.

While it is technically possible for a Covid-19 vaccine to be available in 12 months, there are multiple factors that suggest this to be closer to wishful thinking than anything remotely certain.

Figure 1: Industry Perspective on Vaccine Development. Credit: GlobalData

GlobalData is this websites parent business intelligence company.

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Covid-19 vaccine will be developed within 12 months, poll participants said - Pharmaceutical Technology

YELLOWSTONE NATIONAL PARK Before Covid-19 ever existed and long before we started using the phrases, Stay at Home and Shelter in Place in daily conversation, Yellowstone National Park had already contributed to the battle over the deadly virus.

It all started in Yellowstones famous, colorful and numerous hot springs.

Yellowstone has the largest concentration of hydrothermal features in the world, said Annie Carlson, Yellowstone National Park Research Coordinator.

Its in those hot spots where unique heat loving bacteria called thermophiles and extremophiles, have evolved. Anyone can see many of those springs just by touring the parks thermal features on designated boardwalks.

Back in the mid 1960s researcher Thomas Brock was taking a hot spring walk just like many people do every year. But he was intrigued by the organisms living in the extremely hot and acidic springs. Shortly afterward he identified a unique bacteria.

The bacterial species that they identified is called Thermus Aquaticus. Said Carlson.

And thats where the connection to the pandemic comes in. In 1985, scientists took an enzyme from that bacteria to invent a new laboratory process.

The enzymes solved a problem in DNA labs. Up until then, the enzymes used to map DNA were all destroyed by the heat the process generated. The Yellowstone enzyme was different because it thrives in such hot environments.

This gave researchers a way to quickly replicate small DNA strands in a process called PCR or a polymerase chain reaction.

So, one key molecule from a Yellowstone hot spring led to the DNA mapping we now take for granted in crime study, genealogy, and medicine, including vaccines, like the one being developed for Covid-19.

Carlson said, Medically its a very important technique.

That breakthrough, though decades old, still has a lot of potential. Carlson said, You can imagine that with any infectious disease in the future that could be used.

Yellowstones unique heat loving bacteria are so promising that a quarter of all the annual research permits in the park are issued to scientists looking for new and valuable bacteria.

Carlson said those scientists, Are really pushing the envelope with extremophile and thermophile research.

That research goes way beyond medicine. Some scientists are searching for the origins of life on earth and others are even looking for clues to life that may exist on other planets. The next time you visit Yellowstone, you may see some of those scientists, who have received special permits to carefully tiptoe between thermal areas sampling the unique life that lives there.

DIGITAL EXTRA: Extended interview with YNP Research Coordinator Annie Carlson

EXTENDED INTERVIEW with Annie Carlson, YNP Research Coordinator

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Local News Yellowstone enzyme may be key tool in creation of Covid-19 vaccine John Sherer - KBZK Bozeman News

As companies race against time to bring to market a vaccine for the new coronavirus SARS-CoV-2 that causes COVID-19, three contenders have emerged asfrontrunners, having advanced their candidates into the clinics.

Moderna Inc (NASDAQ: MRNA), Inovio Pharmaceuticals Inc (NASDAQ: INO) and CanSino Biological Inc./Beijing Institute of Biotechnology are those that have moved out of the crowd, even as the rest are either testing vaccines in labs,in vitro, or in animals in the preclinical stage.

Here's brief on the vaccine programs:

Moderna

Name of the vaccine candidate: mRNA-1273

Type: messenger RNA vaccine

Status: enrollment ongoing inPhase 1 study

Moderna is working on mRNA-1273 in collaboration with the NIH's National Institute of Allergy and Infectious Diseases. The vaccine encodes a prefusion-stabilized form of the SARS-CoV-2 spike protein.

The company said it took just 25 days to gofrom sequence selection to manufacturing of the vaccine, and 63 days from sequence selection to start of the Phase 1 trial.

Benzinga is covering every angle of how the coronavirus affects the financial world.For daily updates,sign up for our coronavirus newsletter.

Source: Moderna

Study participants will receive two doses of the vaccine via intramuscular injection in the upper arm about 28 days apart, with dosages of 25 mcg, or 100 mcg or 250 mcg.

The company's timeline suggests a commercial launch timeline of 12-18 months. Under emergency use, the vaccine could be available to some people and health care workers in the fall of 2020.

See also: Gilead Analysts Break Down Remdesivir Data Readout From Compassionate Use

Inovio

Name of the vaccine candidate: INO-4800

Type: DNA vaccine

Status: enrollment and dosing ongoing in Phase 1 study

Inovio said it designed the vaccine within three hours of the release of the virus genomeusing its P2 MERS candidate. The program is in part funded by Coalition For Epidemic Preparedness Innovations and the Bill and Melinda Gates foundation.

Inovio said April 6 the FDA accepted its IND for INO-4800, signaling the regulatory agency's nod for undertaking clinical trials.

The company plans to enroll 40 healthy volunteers in Philadelphia and Kansas City. To assessinitial immune responses and safety, each participant is to receive two doses of the vaccine candidate four weeks apart.

Inovio also said it has manufactured thousands of doses to support the ongoing Phase 1 study as well as aplanned Phase 2 study. The company said is also working to scale up manufacturing so that it has about 1 million doses of INO-4800 available by year's end for additional trials and emergency use.

CanSino Biological Inc./Beijing Institute of Biotechnology

Name of the vaccine candidate: Ad5-nCoV

Type: Adenovirus Type 5 Vector (non-replicating vector type)

Status: Phase 1/2 studies

The vaccine candidate is based on the viral vector vaccine technology platform previously used to develop an Ebola vaccine.

Pfizer Inc. (NYSE: PFE) and Arcturus Therapeutics Ltd (NASDAQ: ARCT) shared atimeline for their jointly developed mRNA vaccine last week. The companies are targeting an end-of-April schedule for starting human trials.

Related Link: GlaxoSmithKline, Sanofi Collaborate On COVID-19 Vaccine Development: What You Should Know

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3 Frontrunners In COVID-19 Vaccine Development: What You Need To Know - Yahoo Finance

So far, Australia has been doing pretty well in the fight against COVID-19. Using a combination of social distancing, tight travel restrictions and contact tracing, the country has kept its death toll under 100 people and seems to be leveling off its new cases. Its even managed to avoid closing schools. But despite the relatively minor impact the novel coronavirus has had on life in Australia, medical workers are still running low on masks, gloves and gowns.

Suddenly it feels like a house of cards, said Simon Quilty, senior staff specialist at Alice Springs Hospital in Australias Northern Territory. We havent quite [run out of personal protective equipment], but weve come very close to it. We dont even have the pandemic. If we do get a pandemic, were fucked.

All around the world, whether hard-hit by the virus or not, countries are running low on crucial supplies. And while shortages are largely confined to disposable medical items for now personal protective equipment (PPE), swabs, chemicals used for COVID-19 testing experts say other shortages are likely. The spread of SARS-CoV-2 (the virus that causes COVID-19) is affecting the way we manufacture all sorts of products, and the way we get those products to where theyre needed. People who study these supply chains have seen problems coming for years. Now theyre scrambling to get ahead of the pandemic, before it ends up affecting even our ability to produce the vaccines we hope will stop the disease in its tracks.

Up until a few weeks ago, I knew very little about the supply chain, said Megan Ranney, a professor of emergency medicine at Brown University. It always just worked. But Ive learned a bunch, and its more fragile than we ever thought possible. COVID-19 has forced her and lots of other hospitalists around the country to become supply chain experts on the fly.

A supply chain is a fancy term to describe how products get made and moved all around the globe. Its a simple concept, but not a simple process. Supply chains arent a conveyor belt theyre a ballet. And there are many, many ways this spectacular show can fall flat on its face. The production of a single item often involves multiple factories in several different countries and depends on speedy, reliable international shipping to get each piece to the right place at the right time and then to the buyers exactly when they need it.

In fact, experts in both manufacturing and medicine have spent years warning of the risks a pandemic or another major disaster could cause to supply chains. In 2011, for instance, Quilty documented that the hospital where he worked at the time had less than a 30 days supply of penicillin and many other crucial pharmaceutical drugs. A 2017 paper by scientists with the Centers for Disease Control and Prevention pointed out that PPE supplies had run into problems during the 2009 H1N1 influenza pandemic and the 2014 Ebola virus epidemic, and warned that the system wasnt prepared to handle a sudden increase in demand. Multiple reports have been published on how avian flu pandemics could disrupt everything from computer manufacturing to the global food supply.

PPE is the canary in the coal mine, Ranney said. She, and other experts, told me that right now, thats the main place were seeing supply chains break down. But those same issues apply to damn near everything else we make and sell. The longer the pandemic goes on, the more products will be affected.

There are three big problems with the global supply chains, experts told me. First, the push toward lowest-cost production means a lot of cheap goods and cheap components of more valuable goods are made in places with low-cost labor. When those countries experience a pandemic outbreak or when a pandemic interrupts transport from those countries it creates a bottleneck.

Around half the worlds face masks came from China before the novel coronavirus pandemic began. The virus interrupted manufacturing there early on, Ranney said. Now, China can make masks again, but demand has jumped all over the world, and there are shipping delays. Several companies have told her to expect deliveries to take three or four weeks. In the meantime, shes been left to sort through sketchy, back-alley PPE dealers, some of whom produce low-quality masks that either fall apart or dont filter properly on testing. Other would-be suppliers have turned out to be basically the high-stakes equivalent of one of those youve inherited $3,000,000! email scams.

American manufacturing companies are starting to switch over production lines to make masks and other protective equipment here but thats not a quick process and presents its own complications. For example, the nonwoven textiles that N95 respirator masks use to filter out viruses have to be made on special machines. There are only a few of those machines in the whole world, said Julie Swann, professor of industrial and systems engineering at North Carolina State University. And you cant just go buy a new one off the shelf. Her university is producing some of this material now. But not at the volume youd make at a large manufacturer, she said.

The second problem is that a global pandemic causes sudden spikes in demand for certain products. Production is designed for steady demand with predictable increases and decreases. A big, unforeseen event, like a pandemic, throws everything out of whack, said Adegoke Oke, professor of supply chain management at Arizona State Universitys school of business. Take our toilet paper woes. That supply chain didnt account for sudden, nationwide increases in having to pee at home. It also didnt anticipate every office in the nation suddenly holding it, indefinitely. You might think that the demand in one sector could be met by the excess from the other, but it doesnt work that way. The type of toilet paper you use in the office the big rolls are totally different from what you use at home, Oke said. They require different supply chains and different manufacturing lines.

And when manufacturing capacity cant keep up with a sudden surge in demand, there are no emergency backup supply closets to raid. Thats because of a popular and widespread business practice called just in time supply. Essentially, it means that businesses from hospitals to grocery stores keep only a small amount of supplies on hand at any given time enough to get through a couple of weeks or a month. Just-in-time saves money on warehouse storage, energy and staffing, but it works only if the supplies can be produced and delivered when you need them. Its been very successful, Oke said. But at a time like this, the last thing you want is just-in-time.

Finally, supply chains are also getting disrupted in some truly surprising ways ripple effects that spread from one industry to another. Take the transportation of goods. Turns out, its pretty dependent on European tourism 80 percent of the air cargo capacity across the Atlantic comes aboard passenger flights. When those all but stopped, it created a transportation bottleneck for manufacturing, said James Robinson, an independent consultant who spent 30 years working in vaccine manufacturing for companies like Merck. Airlines are turning their empty passenger jets into cargo flights, but that takes retrofitting and time and money and its going to increase the cost of shipping, Robinson said.

Then theres all the food being trashed in response to a pandemic thats cleared grocery shelves nationwide. The same parallel but separate home and business supply chains that affect the toilet paper supply also affect food. What people eat in a restaurant or at school and how much of it they eat isnt the same as what they eat at home. And the farmers who have typically supplied commercial kitchens dont have the sales, marketing, packaging and transport networks in place to get their food where its needed. Fresh vegetables and milk have simply been thrown out. And thats not to mention facilities closing when food industry workers are taken out by illness or migrant farm workers not being able to cross borders at future harvest times things that researchers have long predicted could cause food shortages in the U.S. during a time of pandemic. The food supply could be vulnerable, Swann said. As much as I dont want to scare people.

These supply chain issues can also create a weird sort of feedback loop: The virus increases demand for certain products, which jumbles supply chains for those products, which in turn hampers efforts to use those products to keep the virus in check. And that gives the virus time to beat up the economy even more.

Which is all to say that problems with the PPE supply could be only the beginning. As people like Robinson try to coordinate what will become an international effort to manufacture a COVID-19 vaccine in the months ahead, for example, theyre looking at whats going on with products like PPE knowing that the same things could happen to vaccines.

A vaccine manufacturer like Sanofi might source several thousand ingredients to make a vaccine, Robinson told me. But each material is coming from factories with hundreds of sources, and those sources have sources. Like the connection between holiday travel and international shipping, supply chains for vaccines can end in unexpected places like a Chilean tree farm.

Robinson is vice chair of the scientific advisory committee for the Coalition for Epidemic Preparedness Innovations, an international organization that helps coordinate funding and research for vaccines against emerging infectious diseases. CEPI is involved in the development of 10 different coronavirus vaccines, and Robinson expects at least three of those will eventually make it to widespread use. One of these vaccines, though, uses an adjuvant a substance to help strengthen the bodys immune response to a vaccine that contains an oil extracted from the Quillaja saponaria Molina tree, common to Peru, Chile and Bolivia. The bark is harvested only between November and January each year, so this years harvest didnt take the new coronavirus into account. Theres only so much of that adjuvant available until next year, Robinson said.

Other expected supply chain issues with vaccines are shaped by years of international trade patterns. For example, doses of vaccines are delivered in glass vials, and theres been a global shortage of glass stretching back to at least 2015. The medical glass industry was just beginning to catch up with increased demand, Robinson said, and now, novel coronavirus vaccines will create additional pressure. Even if the vaccine is loaded into 10-dose vials, thats still hundreds of millions of vials that will be needed, he told me. Janssen, a division of Johnson & Johnson, is developing a novel coronavirus vaccine that Robinson regards as one of the most promising. [Janssen has] already preordered 250 million vials, and that might be all thats out there, he told me. Were trying to procure another 200 million.

What it boils down to is that even the vaccine industry isnt prepared for a sudden increase in demand on this scale which would likely far outpace even the spikes associated with a bad flu season. In 2009, H1N1 rapidly increased manufacturing and got up to 400 million doses in a year. But for a pandemic, we might need billions, Robinson said.

The biggest thing experts are taking away from all this is the weakness of that just-in-time supply chain. In lean terminology, inventory is waste because its supply you arent using, Robinson said. But now, when demand is sharply rising, that inventory would be helpful and so many industries are tied together that when one runs out of supply it affects the ability of other industries to keep functioning.

Production can be ramped up, and it is. But it takes time and investment and its important to remember that those investments are a risk. We might need American-made masks now, but will we keep buying them after the threat of COVID-19 has passed? Or will we revert to just-in-time supply from cheaper factories overseas? History suggests the latter. During previous epidemics of influenza, Texas-based company Prestige Ameritech saw demand soar, Swann told me. But it proved to be a boom and bust. The company invested in new machines to meet demand during the 2009 H1N1 pandemic, Swann said. And then they almost went out of business later because [the Texas companys product] was a little more expensive than the ones from China, she said. We need to be willing to pay a little more during times of peace without crisis so we have supply available during crisis.

Continued here:

How COVID-19 Is Wreaking Havoc On Our Ability To Make Things Including Vaccines - FiveThirtyEight

Oxford Universityscientistsare to begin human trialsof a potentialcoronavirusvaccine next week.

Researchers said the jab could be ready to be rolled out for emergency use by the autumn followingsignificant progress in the early stages of development.

The Oxford team has tested the vaccine successfully on several animal species.

Sharing the full story, not just the headlines

TheWorld HealthOrganisation(WHO) has reported that more than 70 vaccines are being developed globally for Covid-19, which has infected morethantwo million people and killed128,886 across the world.

However, experts have cautioned it could take at least18 months to fully develop a jab that can be made available to millions people.

The Oxford teamjoin three other groups of researchers two in the United States and one in China in beginningtrialson humans.

Their projecthasrecruited 510 people, ranging from18 to 55 years old, to take part in the trials, said lead researcherProfessor Adrian Hill.

We are going into human trials next week. We have tested the vaccine in several different animal species, he added.

We have taken a fairly cautious approach, but a rapid one to assess the vaccine that we are developing.

Professor Sarah Gilbert, a vaccinologistat Oxford, has said she is80 per cent confident it will be a success.

There is now hope that thejab, developed by the clinical teams at the Jenner Institute and Oxford Vaccine Group, couldbe ready from as early asSeptember.

No hype, just the advice and analysis you need

However, Professor Hill saidthe team must continue to increase fundraising in order toaccelerate development.

Were a university, we have a very small in house manufacturing facility that can do dozens of doses. Thats not good enough to supply the world, obviously, he told the BBC World Service.

We are working with manufacturing organisations and paying them to start the process now.

So by the time July, August, September comes whenever this is looking good we should have the vaccine to start deploying under emergency use recommendations.

Thats a different approval process to commercial supply, which often takes many more years.

There is no point in making a vaccine that you cant scale up and may only get 100,000 doses for after a huge amount of investment.

You need a technology that allows you to make not millions but ideally billions of doses over a year.

The UKs chief scientific adviser Sir PatrickVallancehas saidit would be very lucky if acoronavirus vaccine was widely available within a year.

Sir Patrick told ITV:A vaccine that can be used generally wed be very lucky to get one within a year.

Original post:

Coronavirus: Oxford University set to begin human trials of Covid-19 vaccine - The Independent

The Research Brief is a short take about interesting academic work.

We are both biotechnology researchers and are currently seeking to repurpose an existing medical manufacturing platform to quickly develop a vaccine candidate for COVID-19.

This process is used for the treatment of blood products such as plasma, platelets and whole blood to prevent disease transmission when people receive transfused blood. It utilizes a common food ingredient, vitamin B2, or riboflavin, which is a light-sensitive chemical. When used in combination with ultraviolet light of specific wavelengths, B2 can alter genetic material, whether RNA or DNA, of infectious pathogens in the blood, making them unable to transmit disease.

Those genetic changes prevent pathogens, such as viral, bacterial and parasitic contaminants, in blood from replicating. By stopping the replication process, the method protects people from disease they could acquire through a blood transfusion.

Heres how we believe this technology can be applied to COVID-19 virus: When creating a vaccine candidate, the goal is to destroy the replication potential of the virus while preserving its proteins and antigens, the substances in the virus that prompt the body to produce antibodies. The presence of those proteins and antigens allows the body to recognize the virus as foreign and mount an immune response against it.

When this method is applied to a pure virus grown in cell culture, the B2 damages the viruss genetic material and thus blocks it from replicating. But the B2 treatment leaves the rest of the virus notably the viral proteins undamaged. That is important because the vaccine needs to contain proteins that appear on an infecting virus in order for a person to produce effective antibodies and protect against the disease.

Vaccines require an inactive form of a virus that cannot cause disease to stimulate the immune system. In 2009, during the H1N1 influenza outbreak, the U.S. experienced shortages in the manufacturing of needed vaccines, as the need to grow the virus was in high demand and the manufacturing plants that required the use of eggs to grow the virus were insufficient.

This resulted in the expansion of new ways to manufacture vaccines, some of which are now in use. Yet, there is still a lag time in the production of needed vaccines for the current coronavirus outbreak.

Most methods that are used today to prepare inactivated viruses employ chemicals that are both toxic and in some cases even pose explosion risk, meaning that facilities have to be constructed and operated in ways that protect workers and the public from their use and exposure.

Riboflavin is a compound that is generally recognized as safe because of its low toxicity in humans and animals and its presence in common products people routinely ingest. Using this approach can make this step in virus production much easier and applicable for use in appropriate biological containment facilities.

Over the last decade, there have been advances in manufacturing and in strategies to rapidly produce a vaccine.

Our work has been made possible by the investments made in the U.S. research infrastructure through the National Institute of Allergy and Infectious Diseases in order to expand research and manufacturing capacity and to address concerns over the potential threat of bioterrorism. It led to the construction of a manufacturing plant and research labs which are currently used by industry, government and academic partners pursuing manufacturing and process development for vaccines, therapeutics and diagnostic reagents.

Although the threat from bioterrorism never materialized to the extent that was initially envisioned, there is a need for rapid vaccine development to address emerging pathogens that threaten human health on a global basis, such as Zika.

Our vaccine construct, which we call SolaVAX, is undergoing animal testing and further laboratory characterization, such as studying the nature of the damage to the viral RNA that this process induces and its immunological effect when given to animals. We began our initial vaccine challenge studies earlier this month. These tests will determine if we can protect animals that are vaccinated with SolaVAX from developing the disease when they are later exposed to the live virus. This work is a first step on the path to human clinical evaluation. We also possess the nonprofit BioMARC manufacturing operation at Colorado State University, where testing and development of this inactivation method for vaccine production can be piloted.

If initial results in animal testing and pilot production of the vaccine are positive, the next steps into human clinical testing and evaluation and ultimate regulatory approvals represent the next major hurdle.

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Researchers seek to repurpose an existing manufacturing platform to produce a COVID-19 vaccine - The Conversation US