Moderna test COVID vaccine induces immune response, researchers say – Nikkei Asian Review

CHICAGO (Reuters) — Moderna Inc’s experimental vaccine for COVID-19 showed it was safe and provoked immune responses in all 45 healthy volunteers in an ongoing early-stage study, U.S. researchers reported on Tuesday.

Volunteers who got two doses of the vaccine had high levels of virus-killing antibodies that exceeded the average levels seen in people who had recovered from COVID-19, the team reported in the New England Journal of Medicine.

No study volunteers experienced a serious side effect, but more than half reported mild or moderate reactions such as fatigue, headache, chills, muscle aches or pain at the injection site. These were more likely to occur after the second dose and in people who got the highest dose.

Experts say a vaccine is needed to put an end to the coronavirus pandemic that has sickened millions and caused nearly 575,000 deaths worldwide.

Moderna was the first to start human testing of a vaccine for the novel coronavirus on March 16, 66 days after the genetic sequence of the virus was released.

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, whose researchers developed Moderna’s vaccine candidate, called the results “good news,” noting that the study found no serious adverse events and the vaccine produced “reasonably high” levels of virus-killing or neutralizing antibodies.

“If your vaccine can induce a response comparable with natural infection, that’s a winner,” Fauci said in a telephone interview. “That’s why we’re very pleased by the results.”

Moderna shares jumped more than 15% in after-hours trading on Tuesday.

The U.S. government is supporting Moderna’s vaccine with nearly half a billion dollars and has chosen it as one of the first to enter large-scale human trials. A successful vaccine could be a turning point for Cambridge, Massachusetts-based Moderna, which has never had a licensed product.

Moderna’s shot, mRNA-1273, uses ribonucleic acid (RNA) – a chemical messenger that contains instructions for making proteins. When injected into people, the vaccine instructs cells to make proteins that mimic the outer surface of the coronavirus, which the body recognizes as a foreign invader, and mounts an immune response against.

The results released Tuesday involved three doses of the vaccine, tested in groups of 15 volunteers aged 18-55 who got two shots, 28 days apart. The groups tested 25, 100 or 250 micrograms of the vaccine.

Adverse events after the second dose occurred in seven of the 13 volunteers who got the 25-microgram dose, all 15 participants who received the 100 microgram dose and all 14 who got the 250 microgram dose. In the highest-dose group, three patients had severe reactions such as fever, chills, headache or nausea. One of these had a fever of 103.28 Fahrenheit (39.6 C).

“We didn’t see any events that are characterized as serious adverse events,” said lead author Dr Lisa Jackson of Kaiser Permanente Washington Health Research Institute in Seattle, referring to reactions that require hospitalization or result in death.

In June, Moderna said it selected the 100-microgram dose for its late-stage study to minimize adverse reactions.

At that dose, Moderna said the company is on track to deliver about 500 million doses per year, and possibly up to 1 billion doses per year, starting in 2021, from the company’s internal U.S. manufacturing site and strategic collaboration with Swiss drugmaker Lonza.

“It’s a good first step,” said Dr William Schaffner, a vaccine expert at Vanderbilt University Medical Center who was not involved in the study.

“There’s nothing here that would inhibit one from going ahead to the Phase 2/Phase 3 trials,” he said.

In April, Moderna expanded the Phase 1 trial to include adults over 55, who are more at risk of serious disease, with the aim of enrolling 120 volunteers. Moderna said it will follow study volunteers for a year to look for side effects and check how long immunity lasts.

Moderna started its phase 2 trial in May and expects to start a phase 3 trial on July 27.

Phase 1 trials aim to ensure a treatment is safe and help determine an effective dose. Phase 2 trials test a treatment in a larger group and get an early read on effectiveness. Phase 3 trials are conducted in a large group of individuals to confirm efficacy and identify rare side effects. Moderna’s Phase 3 trial will be conducted in 30,000 volunteers.

New Study Finds This Is Essential For Managing Blood Sugar Levels – mindbodygreen.com

Because of the influence of cortisol levels on managing blood sugar, finding effective ways to relieve stress can help manage blood sugar levels, especially for those with type 2 diabetes.

“Whether it’s a yoga class, taking a walk or reading a book, finding ways to lower your stress levels is important to everyone’s overall health,” says Joseph, who also serves as an assistant professor in the College of Medicine, “especially for those with type 2 diabetes.”

Based on the results of this recent study, Joseph and his team are planning more research: “We have begun a new trial to examine if mindfulness practices can lower blood sugar in those with type 2 diabetes,” he explains.

And while mindfulness practices can be an important part of managing stress, he points out that those aforementioned strategies are always good too. “[Mindfulness] isn’t the only effective form of stress relief. It’s important to find something you enjoy and make it a part of your everyday routine.”

Some of our favorite stress management tools? Using favorite essential oils, following along with short meditations, and developing a breathwork practice (which you can learn with us!) are simple things that can make a big difference for stress levels.

Moderna Sets Date for Start of Coronavirus Vaccine Phase 3 Trial – Motley Fool

Moderna (NASDAQ:MRNA) has a start date — at least an approximate one — for the phase 3 clinical trial of its mRNA-1273 coronavirus vaccine candidate. The highly anticipated trial’s estimated launch is Monday, July 27, according to an entry on the government’s tracking web site ClinicalTrials.gov.

All told, around 30,000 adults of both sexes will be recruited for the study, which should run for approximately three months. Participants will receive one intramuscular injection of either 100 micrograms of mRNA-1273 or a placebo on day 1 and on day 29. The trial will be conducted across 87 locations throughout the U.S.

Gloved hands filling a syringe from a vial.

Image source: Getty Images.

If the trial launches on time, it would fulfill a promise made by Moderna of a July start. Earlier this month, there was speculation that the phase 3 trial would be delayed due to the company’s modifications of the testing protocol. There were also reports that Moderna and government health officials were at odds over various aspects of the trials, although both sides maintain this isn’t the case.

The company, which is relatively new compared to larger peers who are also developing coronavirus vaccine candidates, has never conducted a clinical trial of this size. And unlike many of those rivals, it has never had a single product approved.

Yet the results it has released from earlier testing on mRNA-1273 are very encouraging, and the vaccine candidate is moving rather quickly through the clinical trials process. As a result, numerous healthcare experts and industry observers believe Moderna has a strong chance of being the first to market with a coronavirus vaccine.

Investors seem to be cheered by this latest piece of news. In mid-afternoon trading on Tuesday, Moderna shares were up by 4%, considerably outpacing the gains of the broader stock market.

 

Experimental COVID-19 vaccine safe, generates immune response: NIAID-sponsored Phase 1 trial tested mRNA vaccine – Science Daily

An investigational vaccine, mRNA-1273, designed to protect against SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), was generally well tolerated and prompted neutralizing antibody activity in healthy adults, according to interim results published online today in the New England Journal of Medicine.

The ongoing Phase 1 trial is supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The experimental vaccine is being co-developed by researchers at NIAID and at Moderna, Inc. of Cambridge, Massachusetts. Manufactured by Moderna, mRNA-1273 is designed to induce neutralizing antibodies directed at a portion of the coronavirus “spike” protein, which the virus uses to bind to and enter human cells.

The trial was led by Lisa A. Jackson, M.D., MPH, of Kaiser Permanente Washington Health Research Institute in Seattle, where the first participant received the candidate vaccine on March 16. This interim report details the initial findings from the first 45 participants ages 18 to 55 years enrolled at the study sites in Seattle and at Emory University in Atlanta. Three groups of 15 participants received two intramuscular injections, 28 days apart, of either 25, 100 or 250 micrograms (mcg) of the investigational vaccine. All the participants received one injection; 42 received both scheduled injections.

In April, the trial was expanded to enroll adults older than age 55 years; it now has 120 participants. However, the newly published results cover the 18 to 55-year age group only.

Regarding safety, no serious adverse events were reported. More than half of the participants reported fatigue, headache, chills, myalgia or pain at the injection site. Systemic adverse events were more common following the second vaccination and in those who received the highest vaccine dose. Data on side effects and immune responses at various vaccine dosages informed the doses used or planned for use in the Phase 2 and 3 clinical trials of the investigational vaccine.

The interim analysis includes results of tests measuring levels of vaccine-induced neutralizing activity through day 43 after the second injection. Two doses of vaccine prompted high levels of neutralizing antibody activity that were above the average values seen in convalescent sera obtained from persons with confirmed COVID-19 disease.

A Phase 2 clinical trial of mRNA-1273, sponsored by Moderna, began enrollment in late May. Plans are underway to launch a Phase 3 efficacy trial in July 2020.

Additional information about the Phase 1 clinical trial design is available at ClinicalTrials.gov using the identifier NCT04283461. This trial was supported in part by the NIAID grants UM1AI148373 (Kaiser Permanente Washington), UM1AI148576 (Emory University) and UM1AI148684 (Infectious Diseases Clinical Research Consortium). Funding for the manufacture of mRNA-1273 Phase 1 material was provided by the Coalition for Epidemic Preparedness Innovations (CEPI).

Story Source:

Materials provided by NIH/National Institute of Allergy and Infectious Diseases. Note: Content may be edited for style and length.

The pandemic virus is slowly mutating. But is it getting more dangerous? – Science Magazine

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Data from Dutch mink farms hit by the coronavirus may shed more light on a mutation that has spread widely.

FABIAN BIMMER/REUTERS/Newscom

Science‘s COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.

It’s only a tiny change. At some point early in the pandemic, one of the 30,000 letters in the genome of SARS-CoV-2 changed from an A to a G. Today, that mutation, at position 23,403, has spread around the world. It is found in the vast majority of newly sequenced viruses and has become the center of a burning scientific question: Has the mutation become so common because it helps the virus spread faster? Or is it just coincidence?

More than 6 months into the pandemic, the virus’ potential to evolve in a nastier direction—or, if we’re lucky, become more benign—is unclear. In part that’s because it changes more slowly than most other viruses, giving virologists fewer mutations to study. But some virologists also raise an intriguing possibility: that SARS-CoV-2 was already well adapted to humans when it burst onto the world stage at the end of 2019, having quietly honed its ability to infect people beforehand.

On average, the coronavirus accumulates about two changes per month in its genome. Sequencing SARS-CoV-2 genomes helps researchers follow how the virus spreads. Most of the changes don’t affect how the virus behaves, but a few may change the disease’s transmissibility or severity.

One of the earliest candidates was the wholesale deletion of 382 base pairs in a gene called ORF8, whose function is unknown. First reported by Linfa Wang and others at the Duke-NUS Medical School in Singapore in a March preprint, the deletion has since been reported from Taiwan as well. A deletion in the same gene occurred early in the 2003 severe acute respiratory syndrome (SARS) outbreak, caused by a closely related coronavirus; lab experiments later showed that variant replicates less efficiently than its parent, suggesting the mutation may have slowed the SARS epidemic. Cell culture experiments suggest the mutation does not have the same benign effect in SARS-CoV-2, Wang says, “but there are indications that it may cause milder disease in patients.”

Weak evidence of a moderate effect

The mutation at position 23,403 has drawn the most attention—in part because it changed the virus’ spike, the protein on its surface that attaches to human cells. The mutation changed the amino acid at position 614 of the spike from an aspartic acid (abbreviated D) to a glycine (G), which is why it’s called G614.

In a Cell paper this month, Bette Korber and colleagues at Los Alamos National Laboratory showed that G614 has become more common in almost every nation and region they looked at, whereas D614 is virtually gone (see graphic, below). That might be a sign that it’s outcompeted by G614, but it could also be a coincidence. “Any one mutation may rise to very high frequency across the world, just because of random chance,” says Kristian Andersen, a computational biologist at Scripps Research. “This happens all the time.”

Comparing the spread of different viral variants carrying the two mutations could reveal a difference. The United Kingdom’s COVID-19 Genomics Consortium has sequenced 30,000 SARS-CoV-2 genomes, allowing scientists to compare how fast 43 lineages carrying the G614 mutation and 20 with D614 spread. They estimated that the former grew 1.22 times faster than the latter—but the statistical significance was low.  “Evidence for a difference is weak and if it does exist, the estimated effect is moderate,” says evolutionary biologist Andrew Rambaut of the University of Edinburgh.

Researchers have also turned to cell culture experiments. When Korber’s group engineered so-called viruslike particles to carry one spike protein or the other, the G614 variant appeared to be more efficient at entering cells. Jeremy Luban of the University of Massachusetts Medical School, who has found the same thing, explains that G614 causes a slight change in the shape of the spike,  apparently making it easier for the protein to undergo the structural changes that cause the membranes of the virus and the cell to fuse. “Our data looks like it’s somewhere between three and 10 times more infectious,” Luban says. “That’s a pretty enormous effect.”

That does not mean the mutation has an effect in the real world, says virologist Emma Hodcroft of the University of Basel. In the past, she notes, “We have cases where we really thought that we had evidence for a mutation that was changing viral behavior and as more evidence came, it didn’t seem to be the case.” An increased ability to infect a laboratory cell line may not translate to the billions of diverse cells in a human body, adds Angela Rasmussen, a virologist at Columbia University: “Humans aren’t Vero cells.”

A change for the worse?

A one-letter mutation, rare in February but found in almost every newly sequenced genome today, may make SARS-CoV-2 more transmissible.

60804020011 Jan.Feb.Mar.Apr.May6 Jun.D614G614100%

Korber et al., Cell, DOI: 10.1016/j.cell.2020.06.043, Adapted by N. Desai/Science

Animal experiments are another way to probe the effects of G614. One option, virologist Marion Koopmans of Erasmus Medical Center (EMC) says, would be to infect ferrets with it and D614 and look for differences in how much virus they shed. But infections in ferrets only last about 1 week, Koopmans notes. “The effect would have to be very big to show up in an experiment like that.”

Another idea is to expose uninfected ferrets to animals carrying either of the two variants and see how well they transmit. An uncontrolled transmission experiment has already taken place on Dutch mink farms, where the new coronavirus jumped from humans to minks at least five separate times. Twice it was the D614 variant, and three times G614, Koopmans says. She hopes data from the outbreaks could show whether either one spread faster and wider than the other. But the experiment doesn’t have the rigor of a lab study, she concedes. “We have a natural experiment here. The study design is not optimal.”

Whether G614 is more transmissible or not, it has become the dominant strain and the world is living with it, Rambaut says. Most recent estimates of the virus reproduction number—which denotes how well it spreads—are already based mostly on the mutant strain. “What we don’t know is whether D614 would have been different,“ Rambaut says.

Why so little evolution?

The attention lavished on G614 may obscure a bigger question, however: With the virus having spread to at least 11 million people worldwide, why aren’t more mutations that affect its behavior emerging?

Perhaps there’s just little selection pressure on the virus as it races through millions of immunologically naïve people, scientists say. That could change with the advent of vaccines or new therapies, forcing the virus to evolve. But it could also indicate that the virus has been with people longer than we know, and was spreading before the first known cases in Wuhan, China, in December 2019. “The evolution of this virus to become a human pathogen may have already happened and we missed it,” Rasmussen says.

Wang thinks a version of the virus may have circulated earlier in humans in southern Asia, perhaps flying under the radar because it didn’t cause severe disease. “If it happens in a small or remote village, even with some people dying, nobody is going to know there’s a spillover,” Wang says. The virus could then have infected an animal that was brought to Wuhan and started the pandemic.

At Dutch mink farms, after all, the virus jumped not just from humans to animals, but also back from animals to humans, Wang says. “If that can happen in the Netherlands, surely it can happen in a village in Thailand, or in Yunnan province in southern China.”

Moderna’s COVID-19 Vaccine Set For Final Trial Stage After ‘Promising’ Results – Channels Television

Moderna's COVID-19 Vaccine Set For Final Trial Stage After 'Promising' ResultsModerna's COVID-19 Vaccine Set For Final Trial Stage After 'Promising' Results
In this file photo taken on May 18, 2020, a syringe is pictured on an illustration representation of COVID-19, the disease caused by the novel coronavirus. Photo: JOEL SAGET / AFP

 

The US biotech firm Moderna said Tuesday it would enter the final stage of its human trials for its COVID-19 vaccine on July 27, after promising early results were published in a journal.

The Phase 3 trial will recruit 30,000 participants in the US, with half to receive the vaccine at 100 microgram dose levels, and the other half will receive a placebo.

It is designed to learn whether the vaccine can prevent infection by the SARS-CoV-2 virus, or, if people still get infected, whether it can prevent the infection progressing toward symptoms.

If they do get symptoms, the vaccine can still be considered a success if it stops severe cases of COVID-19.

The study should run until October 27, according to its page on clinicaltrials.gov.

The announcement came after the New England Journal of Medicine on Tuesday published results from the first stage of Moderna’s vaccine trial, which showed the first 45 participants all developed antibodies to the virus.

This file photo shows medical workers in Abuja preparing to test Nigerians for COVID-19. As of July 15, the pandemic had infected 33,616 and a total of over 13.2 million people globally, killing over 575,000 people.

 

Moderna is in pole position in the global race to find a vaccine against the coronavirus, which has infected more than 13.2 million people and killed 570,000.

China’s SinoVac is also at an advanced stage, Phase 2, while the Russian news agency TASS has announced Russian researchers have completed clinical trials on a vaccine, though they have not shared data.

Scientists caution that the first vaccines to come to market may not be the most effective or safest.



The Moderna vaccine belongs to a new class of vaccine that uses genetic material, in the form of RNA, to encode the information needed to grow the virus’ spike protein inside the human body, in order to trigger an immune response.

The spike protein is a part of the virus it uses to invade human cells, but by itself is relatively harmless.

The advantage of this technology is that it bypasses the need to manufacture viral proteins in the lab, shaving months off the standardization process and helping to ramp up mass production.

But no vaccines based on this platform have previously received regulatory approval.

AFP