Breakthrough COVID vaccine tech could help defeat other diseases

By John Miller and Ludwig Burger

ZURICH/FRANKFURT (Reuters) – Breakthrough technology that transforms the body into a virus-zapping vaccine factory is poised to revolutionize the fight against COVID-19 but future pandemics and even cancer could be next, scientists say. The initial success of so-called messenger ribonucleic acid (mRNA) vaccines in late-stage trials by Moderna as well as Pfizer and its German partner BioNTech is the first proof the concept works.

Both experimental vaccines had efficacy rates above 90% based on interim findings, which was far higher than expected and well above the 50% threshold U.S. regulators insist upon for vaccines.

Now scientists say the technology, a slow-motion revolution in the making since the discovery of mRNA nearly 60 years ago, could speed up the development of new vaccines.

The traditional method of creating vaccines – introducing a weakened or dead virus, or a piece of one, to stimulate the body’s immune system – takes over a decade on average, according to a 2013 study. One pandemic flu vaccine took over eight years while a hepatitis B vaccine was nearly 18 years in the making.

Moderna’s vaccine went from gene sequencing to the first human injection in 63 days.

With BioNTech and Pfizer’s COVID-19 candidate on a similar trajectory, both could win regulatory approval this year, barely 12 months since the coronavirus first emerged.

Other companies are pursuing the technology such as Germany’s CureVac also has an mRNA vaccine candidate, though has yet to start a late-stage trial and is hoping it will get the green light after July 2021. “We’ll look back on the advances made in 2020 and say: ‘That was a moment when science really did make a leap forward’,” said Jeremy Farrar, director of the Oxford University Clinical Research Unit, which is backed by the Wellcome Trust.

THE LAST LAUGH

Discovered in 1961, mRNA carries messages from the body’s DNA to its cells, telling them to make the proteins needed for critical functions, such as coordinating biological processes like digestion or fighting disease.

The experimental vaccines from Moderna as well as Pfizer and BioNTech use lab-made mRNA to instruct cells to make the coronavirus’s spike proteins, which spur the immune system into action without replicating like the actual virus. Back in 1990, scientists managed to get mice to generate proteins by injecting mRNA, an early sign of the technology’s potential.

But early proponents such as Katalin Kariko, a Hungarian-born scientist and senior vice president at BioNTech, were hampered by obstacles such as mRNA’s instability in the body and its propensity to cause inflammatory responses.

A breakthrough came around 2005 when Kariko, along with colleagues at the University of Pennsylvania, figured out how to deliver mRNA without kicking the immune system into overdrive.

Still, it took another 15 years – and a pandemic that brought the world’s economy to its knees – to reach the cusp of success. Kariko said her years of dogged pursuit once made her the butt of jokes for some university colleagues.

“The last time they laughed at me and ridiculed me was when they learned that I was going to join BioNTech seven years ago and they realized this company (didn’t) even have a website,” she told Reuters. “But now, they learn of BioNTech and that we can do good things.”

Kariko said her life’s work could pay dividends, not just against COVID-19, but other diseases.

“It could be easier sailing for the next anti-viral product, a vaccine for influenza and other infectious disease,” said Kariko, whose daughter is a U.S. Olympic gold medalist rower.

CANCER NEXT?

Moderna and BioNTech, for example, are also applying mRNA technology to experimental cancer medicines.

BioNTech is testing an anti-melanoma mRNA with Swiss pharmaceutical giant Roche in a Phase II trial.

Among Moderna’s most advanced projects, besides its COVID-19 vaccine, are mRNA compounds to treat ovarian cancer or Myocardial ischemia, which are also in the second test phase.

None of the potential mRNA cancer therapies have reached the critical large-scale Phase III trials, however, and Kariko acknowledges that cancer presents a bigger challenge.

While a virus is a foreign intruder, cancer cells, however malignant, come from within the body, making them tougher to seek out and expose so they can be attacked.

“Sometimes cancer is just caused by gene and chromosome duplication and then everything about it looks normal and the cell is just dividing more than it should,” she said.

For vaccines against infectious diseases, the pharmaceutical industry’s traditional approach has been to whip them up in large bioreactors, a time-consuming, expensive process in facilities that can cost up to $700 million to build.

By contrast, Zoltan Kis, an Imperial College London researcher who models vaccine manufacturing, estimates that one five-liter bioreactor inside a $20 million facility could make a billion doses of some kinds of mRNA vaccines a year.

Drug manufacturer Lonza, enlisted to make ingredients for 400 million doses of Moderna’s vaccine annually at U.S. and Swiss sites, is due to start production this year with manufacturing lines costing $60 million to $70 million each.

“We are producing mRNA at smaller scales and in smaller facilities when compared to traditional larger-scale equipment and facilities,” Andre Goerke, Lonza’s global lead for the Moderna project, told Reuters. “The manufacturing ramp-up is quicker and more economical.”

‘ULTRA-FAST RESPONSE’

Raymond Schiffelers, of University Medical Center Utrecht in the Netherlands, who heads a European Union program for mRNA therapeutics, said the major advantage of the technology was that vaccine developers could mount an “ultra-fast response”.

“Within weeks, testing can start, a major advantage over conventional vaccines,” he said.

The moment a pathogen’s genomic sequence is known, synthetic mRNAs can be designed that encode key parts of the virus, such as the coronavirus’s potentially lethal spike protein.

Risks and challenges for mRNA remain.

Some candidates must be stored at extremely cold temperatures, making delivery potentially difficult in countries with limited infrastructure. They also may be fragile to transport, Schiffelers said.

BioNTech’s vaccine, for example, must be transported at minus 70 degrees Celsius, though Moderna said on Monday it can ship its candidate in normal refrigerators.

Francis Collins, director of the U.S. National Institutes of Health (NIH), which funded Moderna’s vaccine development, also said mRNA vaccines may not be a silver bullet for flu, since it mutates so swiftly that reaching 90% efficacy is unlikely.

But for COVID-19, Collins said mRNA is likely to be a revolution.

“It’s clearly several months faster than any of the other methods,” Collins said. “In a crisis moment, several months really matter.”

(Reporting by John Miller in Zurich, Allison Martell in Toronto, Ludwig Burger in Frankfurt, Kate Kelland in London, Michael Erman in New York, Julie Steenhuysen in Chicago and Marton Dunai in Budapest; Editing by Josephine Mason and David Clarke)

Moderna vaccine is second to exceed expectations; mutated virus may be more vulnerable to new vaccines

By Nancy Lapid

(Reuters) – The following is a roundup of some of the latest scientific studies on the novel coronavirus and efforts to find treatments and vaccines for COVID-19, the illness caused by the virus.

Vaccine from Moderna is second to exceed expectations in pivotal trial

Moderna Inc’s experimental vaccine was 94.5% effective in preventing COVID-19 based on interim data from a late-stage trial, the company said on Monday. That followed last week’s news that Pfizer Inc’s vaccine was also more than 90% effective based on initial data. Pending more safety data and regulatory review, the United States could have two vaccines authorized for emergency use in December. Both vaccines employ synthetic messenger RNA (mRNA), which coaxes cells to make certain virus proteins that the immune system sees as a threat and mounts a response against. Moderna’s trial involved 30,000 racially diverse U.S. adults, including people at high risk for severe COVID-19. Only five of the 95 COVID-19 cases in the initial analysis occurred in participants who received the vaccine, while the rest had received a placebo. The vaccine, administered in two shots 28 days apart, also appeared to prevent cases of severe COVID-19. Side effects, largely occurring after the second shot, included muscle aches, fever, headache and redness at the injection site. Moderna’s vaccine does not need ultra-cold storage like Pfizer’s, making it easier to distribute. Moderna expects it to be stable at normal refrigerator temperatures of 2 to 8 degrees Celsius (36 to 48°F) for 30 days and can be stored for up to 6 months at -20C.

Mutated virus may be more vulnerable to new vaccines

The mutated form of the new coronavirus that is now the most common strain worldwide is more infectious but may also be more vulnerable to vaccines under development, new research suggests. In experiments reported on Thursday in Science, researchers saw that the newer strain, which originated in Europe, is more efficient at infecting airway cells and at making copies of itself, although it does not appear to produce more severe illness. The D614G mutation causes a “flap” to open on the tip of a spike on the surface of the virus, improving its ability to break into cells, but also creating a pathway for antibodies in vaccines to enter the virus and disable it, the researchers explained in a statement. New SARS-CoV-2 mutations are continually emerging, “like the recently discovered mink SARS-CoV-2 cluster 5 variant in Denmark that also encodes D614G,” coauthor Ralph Baric of the University of North Carolina School of Medicine said in the statement. “We must continue to track and understand the consequences of these new mutations on disease severity, transmission, host range and vulnerability to vaccine-induced immunity,” he added.

Paper forms pose coronavirus risk for lab staff

When laboratory personnel are processing COVID-19 tests, there is a small risk that the paper forms accompanying the specimens can be contaminated with the new coronavirus, a new report cautions. Researchers at the Birmingham Public Health Laboratory in the UK analyzed randomly selected paper forms and specimen packaging during a period when the team was processing about 700 COVID-19 tests daily. Of the 37 items they tested, one piece of paperwork carried genetic material from the coronavirus. The form had come from a low-risk hospital ward, and the specimen from the patient was negative for the virus, “indicating contamination may be occurring as a result of environmental or healthcare worker contamination,” the researchers wrote on Thursday in the Journal of Hospital Infection. They call for “stringent laboratory practices” – hand hygiene, appropriate personal protective equipment – and “use of electronic test requesting where possible.”

(Reporting by Nancy Lapid, Julie Steenhuysen and Michael Erman; Editing by Bill Berkrot)

Fauci not advising Biden, sees no reason to quit Trump now: Reuters interview

By Julie Steenhuysen

CHICAGO (Reuters) – Dr. Anthony Fauci, the top U.S. infectious disease expert, said he has had no contact with President-elect Joe Biden’s coronavirus transition team and sees no reason to quit to join that effort when there is so much to do now to fight the surging pandemic.

“I stay in my lane. I’m not a politician. I do public health things,” he said in an interview on Thursday ahead of next week’s Reuters Total Health conference.

Since January, Fauci has served on President Donald Trump’s White House Coronavirus Task Force, a position that has frequently put him at odds with the president, who has sought to downplay the pandemic and focused instead on opening the economy.

“There’s absolutely no reason and no sense at all for me to stop doing something in the middle of a pandemic that is playing a major role in helping us get out of the pandemic,” Fauci said.

His advice for the president-elect, he said, is “exactly the same” as what he is recommending now – social distancing, avoiding crowds, wearing masks, washing hands. “Public health principles don’t change from one month to another or from one administration to another.”

Fauci has served six administrations and came to prominence fighting the AIDS epidemic in the 1980s under President Ronald Reagan.

His “day job” is developing vaccines and therapeutics as director of the National Institute of Allergy and Infectious Diseases, work that is starting to bear fruit.

On Monday, Pfizer Inc and German partner BioNTech SE announced that their experimental coronavirus vaccine was more than 90% effective – significantly higher than most experts had anticipated.

Moderna Inc, a company developing a similar vaccine with support from the White House’s Operation Warp Speed program, is expected to report results from their late-stage vaccine trial in the next week or so.

Both vaccines use messenger RNA (mRNA) technology, an entirely new rapid vaccine platform that uses synthetic genes to trigger an immune response. Older methods typically use some form of inactivated or killed virus particles.

“It was a home run for the Pfizer product, more than 90% – close to 95% – effective. I have every reason to believe that the Moderna product is going to be similar,” Fauci said.

“It’s an almost identical platform to the Pfizer vaccine, so I would not be surprised at all if it was highly effective,” Fauci added.

The next big question about mRNA technology is safety. Fauci took as a good sign the fact that neither the Pfizer trial, which has enrolled more than 43,000 people so far, nor the Moderna trial, which involves 30,000, had to pause to investigate safety issues.

“That’s really good news,” he said. People in both trials will be followed for two years to make sure there are no long-term side effects. Barring that, “I think that the mRNA platform is here to stay,” he predicted.

In spite of the high bar set by the Pfizer vaccine so far, Fauci said he believes there is still “plenty of room for multiple vaccines, even though there may be a modest degree of difference in total efficacy.”

(Reporting by Julie Steenhuysen, Editing by Peter Henderson and Bill Berkrot)

Moderna on track to report COVID-19 vaccine data later this month

By Manas Mishra and Dania Nadeem

(Reuters) – Moderna Inc. said on Wednesday it was on track to report early data from a late-stage trial of its experimental coronavirus vaccine later this month, and could file for U.S. emergency use authorization in early December.

The company may have to wait for a two-month follow up safety data to apply for U.S. emergency use authorization, even after reporting positive interim data on the vaccine’s effectiveness.

Moderna said it expects the safety data in the second half of this month.

Hopes of the world soon getting an effective vaccine against the virus that has killed over a million people were raised on Monday after Pfizer Inc. said its COVID-19 vaccine was more than 90% effective based on interim trial results.

There are no vaccines that have gained global approval yet, although a handful, including Moderna’s, are in late-stage studies.

It was too early to guess how effective Moderna’s vaccine could be, Chief Executive Officer Stephane Bancel said at a Credit Suisse conference.

The world would have to wait for more data to understand whether use of a particular vaccine would be more widespread, Bancel said.

Moderna, which uses a technology similar to Pfizer’s, finished enrolling 30,000 volunteers in its late-stage study last month.

Public health experts have said it is likely that more than one vaccine would be needed to control the pandemic.

(Reporting by Manas Mishra and Dania Nadeem in Bengaluru; Editing by Krishna Chandra Eluri, Saumyadeb Chakrabarty and Sriraj Kalluvila)

Q&A: Where are we in the COVID-19 vaccine race?

(Reuters) – Drugmakers and research centers around the world are working on COVID-19 vaccines, with large global trials of several of the candidates involving tens of thousands of participants well underway.

The following is what we know about the race to deliver vaccines to help end the coronavirus pandemic that has claimed over 1.26 million lives worldwide:

Who is furthest along?

U.S. drugmaker Pfizer Inc and German partner BioNTech SE were the first to release data showing on Monday that their vaccine worked in a large, late-stage clinical trial.

Russia’s sovereign wealth fund published interim late-stage trial results for its Sputnik V vaccine on Wednesday showing the shot is 92% effective at protecting people from COVID-19.

The next data releases will likely be from U.S. biotech firm Moderna Inc, possibly in November, and from Britain-based AstraZeneca Plc with the University of Oxford in November or December. Johnson & Johnson says it is on track to deliver data this year.

What happens in these trials?

The companies are testing their vaccines against a placebo – typically saline solution – in healthy volunteers to see if the rate of COVID-19 infection among those who got the vaccine is significantly lower than in those who received the dummy shot.

Why is Pfizer ahead with its data?

The trials rely on subjects becoming naturally infected with the coronavirus, so how long it takes to generate results largely depends on how pervasive the virus is where trials are being conducted. Each drugmaker has targeted a specific number of infections to trigger a first analysis of their data.

Pfizer said its interim analysis was conducted after 94 participants in the trial developed COVID-19 while Russia’s examination was conducted after 20 participants in the trial developed the disease.

AstraZeneca said last week a slowdown in infections during the summer is delaying data analysis for its UK trial.

COVID-19 cases, however, soared in October and early November, setting daily records in the United States and Europe.

How well are the vaccines supposed to work?

The World Health Organization has recommended a minimum standard for effectiveness of at least 50%. The United States and some other regulators are following that guideline – which means there must be at least twice as many infections among volunteers who received a placebo as among those in the vaccine group. The European Medicines Agency has said it may accept a lower efficacy level.

Pfizer and Russia both said their vaccines are more than 90% effective against COVID-19.

When will regulators rule on safety and efficacy?

Regulators review vaccines after companies submit applications seeking either emergency use authorization (EUA) or formal approval.

The earliest the U.S. Food and Drug Administration could make a decision is in December because Pfizer/BioNTech and Moderna do not expect to have enough safety data until the second half of November. The FDA has asked companies to watch trial participants for side effects for two months after receiving a final vaccine dose.

Regulators for Europe, the United Kingdom and Canada are considering data on a rolling basis, as it becomes available. They expect to conduct expedited reviews as well. It is not clear when companies will submit efficacy data to these agencies or when the agencies would make a decision.

Could these be the first widely available coronavirus vaccines?

Yes, although China is on a similar timeline. The country launched an emergency use program in July aimed at essential workers and others at high risk of infection that has vaccinated hundreds of thousands of people.

At least four vaccines are far along including those from China National Biotec Group (CNBG), CanSino Biologics and Sinovac. Sinovac and CNBG have said to expect early trial data as soon as November.

Russia has also given the Sputnik V vaccine developed by the Gamaleya Institute to 10,000 members of the general population considered at high risk of contracting the virus.

In late October, the director of the Gamaleya Institute, Alexander Gintsburg, said 20,000 volunteers had received the first shot so far and 9,000 the second.

(Reporting by Carl O’Donnell in New York; Additional reporting by Julie Steenhuysen in Chicago, Michael Erman in New York, Ludwig Burger in Frankfurt, Alistair Smout in London and Polina Ivanova in Moscow; Editing by Caroline Humer, Bill Berkrot, Edwina Gibbs, David Clarke and Josephine Mason)

U.S. has a plan to start Pfizer vaccine shots in December: Health Secretary Azar

By Doina Chiacu and Deena Beasley

WASHINGTON (Reuters) – If Pfizer Inc. submits the positive initial data from its COVID-19 vaccine trial to health regulators as quickly as expected, the U.S. government plans to begin vaccinating Americans in December, Health Secretary Alex Azar said on Tuesday.

Pfizer on Monday said the vaccine it has been developing with German partner BioNTech SE was 90% effective against COVID-19, based on an early look at results from its large, late-stage trial.

The U.S. drugmaker said it expects to have safety data as soon as next week that it needs to apply for emergency use authorization (EUA) with the U.S. Food and Drug Administration.

Upon FDA authorization, the United States would receive about 20 million doses of the Pfizer vaccine per month, Azar said on a call with reporters, noting that HHS could being procuring supplies at the end of this month.

The United States has a $1.95 billion contract for 100 million doses of the Pfizer vaccine – enough to inoculate 50 million people – with an option to acquire 500 million more.

Earlier on Tuesday, Azar said on CNBC that final decisions are subject to a close look at the vaccine efficacy data.

Based on recommendations to the government, it will likely start with inoculations of the elderly in nursing homes and assisted living facilities, healthcare workers and first responders, with a goal to complete those shots by the end of January.

Top U.S. infectious disease expert Anthony Fauci also said in an interview with MSNBC that he expects the doses of the vaccine to be available for certain high priority groups in December.

Azar said he anticipates there will soon be more vaccines to protect against COVID-19 from other companies, including Moderna Inc <MRNA.O>, which is expected to announce interim results of a large trial of its experimental vaccine at the end of the month.

“By the end of March, early April, we expect to have enough for every American who would like to be vaccinated,” Azar told CBNC.

ANTIBODY DRUG DISTRIBUTION

Azar also said the U.S. government would begin distribution of Eli Lilly and Co’s antibody treatment this week, starting first in areas with the highest numbers of hospitalized COVID-19 patients and overall cases.

The treatment, which is administered by infusion, received an EUA on Monday.

“We’ll ensure equitable distribution, and we’ll work tightly with our governors,” Azar said. He said the government will use the same process employed to distribute remdesivir, an antiviral drug from Gilead Sciences Inc used to treat people hospitalized with COVID-19.

According to the Health and Human Services website, the agency will ship more than 79,000 doses of the antibody therapy this week, with the largest number going to Wisconsin, Texas, California, and Illinois.

The United States has purchased 300,000 doses of the treatment for this year and has an option to buy an additional 650,000 doses next year.

Azar said health officials and Eli Lilly were exploring ways to provide the treatment outside of hospitals, including through outpatient infusion centers.

Fauci described the Lilly treatment as “an important first step in the development and distribution of interventions that are given early in the course of disease.”

(Reporting by Doina Chiacu in Washington, Caroline Humer and Carl O’Donnell in New York, Deena Beasley in Los Angeles and Manojna Maddipatla in Bengaluru; Editing by Andrew Heavens, Alexandra Hudson and Bill Berkrot)

Exclusive: New global lab network will compare COVID-19 vaccines head-to-head

By Kate Kelland

LONDON (Reuters) – A major non-profit health emergencies group has set up a global laboratory network to assess data from potential COVID-19 vaccines, allowing scientists and drugmakers to compare them and speed up selection of the most effective shots.

Speaking to Reuters ahead of announcing the labs involved, Melanie Saville, director of vaccine R&D at the Coalition for Epidemic Preparedness Innovations (CEPI), said the idea was to “compare apples with apples” as drugmakers race to develop an effective shot to help control the COVID-19 pandemic.

The centralized network is the first of its kind to be set up in response to a pandemic.

In a network spanning Europe, Asia and North America, the labs will centralize analysis of samples from trials of COVID-19 candidates “as though vaccines are all being tested under one roof”, Saville said, aiming to minimize the risk of variation in results.

“When you start off (with developing potential new vaccines) especially with a new disease, everyone develops their own assays, they all use different protocols and different reagents – so while you get a readout, the ability to compare between different candidates is very difficult,” she told Reuters.

“By taking the centralized lab approach … it will give us a chance to really make sure we are comparing apples with apples.”

The CEPI network will initially involve six labs, one each in Canada, Britain, Italy, the Netherlands, Bangladesh and India, Saville said.

Hundreds of potential COVID-19 vaccines are in various stages of development around the world, with shots developed in Russia and China already being deployed before full efficacy trials have been done, and front-runners from Pfizer, Moderna and AstraZeneca likely to have final-stage trial results before year-end.

Typically, the immunogenicity of potential vaccines is assessed in individual lab analyses, which aim to see whether biomarkers of immune response – such as antibodies and T-cell responses – are produced after clinical trial volunteers receive a dose, or doses, of the vaccine candidate.

But with more than 320 COVID-19 vaccine candidates in the works, Saville said, the many differences in data collection and evaluation methods are an issue.

As well as potential variations in markers of immunity, there are differences in how and where samples are collected, transported and stored – all of which can impact the quality and usefulness of the data produced, and make comparisons tricky.

And with a range of different vaccine technologies being explored – from viral vector vaccines to ones based on messenger RNA – standard evaluation of their true potential “becomes very complex”, she said.

“With hundreds of COVID-19 vaccines in development … it’s essential that we have a system that can reliably evaluate and compare the immune response of candidates currently undergoing testing,” she said.

By centralizing the analysis in a lab network, much of what Saville called the “inter-laboratory variability” can be removed, allowing for head-to-head comparisons.

CEPI says all developers of potential COVID-19 vaccines can use the centralized lab network for free to assess their candidates against a common protocol. For now, the network will assess samples from early-stage vaccine candidate testing and first and second stage human trials, but CEPI said it hoped to expand its capacity to late stage (Phase III) trial data in the coming months.

Results produced by the network will be sent back to the developer, with neither CEPI nor the network owning the data.

CEPI itself is co-funding nine of the potential COVID-19 vaccines in development, including candidates from Moderna, AstraZeneca, Novavax and CureVac.

(Reporting by Kate Kelland, editing by Mark Potter)

Factbox: Latest on the worldwide spread of coronavirus

(Reuters) – Coronavirus infections slowed in Australia and New Zealand, while Britain said it was at a “tipping point” on COVID-19 as European countries mulled tightening restrictions to curb a sharp resurgence in cases.

EUROPE

* Britain is at a tipping point on COVID-19, health minister Matt Hancock said, warning that a second national lockdown could be imposed if people don’t follow government rules designed to stop the spread of the virus.

* The Czech government could declare a state of emergency if a recent spike in cases continues in the coming days, Health Minister Adam Vojtech said.

* Protesters in some poorer areas of Madrid that are facing a lockdown to stem a soaring infection rate took to the streets on Sunday to call for better health provisions, complaining of discrimination by the authorities.

* Russia reported 6,148 new cases on Sunday, the second straight day when the daily number of cases exceeded 6,000.

* French health authorities reported 10,569 new confirmed COVID-19 cases on Sunday, down from the previous day’s record increase of 13,498.

ASIA-PACIFIC

* Schools in Seoul and nearby areas resumed in-person classes for the first time in almost a month after daily cases dropped to the lowest levels since mid-August.

* Australia’s coronavirus hotspot of Victoria reported on Monday its lowest daily rise in infections in three months, although state Premier Daniel Andrews said there were no plans yet to ease restrictions sooner than expected.

* New Zealand Prime Minister Jacinda Ardern lifted all coronavirus restrictions across the country, except in second-wave hotspot Auckland, as the number of new infections slowed to a trickle.

AMERICAS

* The United States set a one-day record with over 1 million coronavirus diagnostic tests being performed, but the country needs 6 million to 10 million a day to bring outbreaks under control, according to various experts.

* Brazil and Argentina, Latin American nations seeking more time to commit to the global COVID-19 vaccine facility known as COVAX, said they intend to do so as soon as possible after missing Friday’s deadline.

MIDDLE EAST AND AFRICA

* Morocco signed a deal with Russia’s R-Pharm to buy a COVID-19 vaccine produced under a license from Britain’s AstraZeneca, the health ministry said, as its total number of cases approached 100,000.

* Israel entered a second nationwide lockdown at the onset of the Jewish high-holiday season, forcing residents to stay mostly at home amid a resurgence in new cases.

MEDICAL DEVELOPMENTS

* Moderna Inc said it was on track to produce 20 million doses of its experimental coronavirus vaccine by the end of the year, while maintaining its goal of readying 500 million to 1 billion doses in 2021.

ECONOMIC IMPACT

* British manufacturers see no evidence of a ‘V’-shaped recovery from the pandemic underway and many are planning to slash investment, a business survey showed.

(Compiled by Devika Syamnath and Alex Richardson; Edited by Shounak Dasgupta)

Explainer: When will COVID-19 vaccines be generally available in the U.S.?

By Carl O’Donnell and Michael Erman

(Reuters) – U.S. President Donald Trump and the head of the Centers for Disease Control and Prevention (CDC) this week disagreed about when a COVID-19 vaccine would become widely available. Trump has said one could initially be available by the Nov. 3 election, while the CDC director said vaccines were likely to reach the general public around mid-2021, an assessment more in line with most experts.

WHAT DOES IT MEAN FOR A VACCINE TO BE GENERALLY AVAILABLE?

General availability is when every American who wants the vaccine can get it. There are currently no COVID-19 vaccines approved by U.S. regulators, although a handful are in late-stage trials to prove they are safe and effective.

Experts estimate that at least 70% of roughly 330 million Americans would need to be immune through a vaccine or prior infection to achieve what is known as herd immunity, which occurs when enough people are immune to prevent the spread of the virus to those unable to get a vaccine.

HOW LONG BEFORE VACCINE PRODUCTION IS FULLY RAMPED UP?

Most vaccines in development will require two doses per person.

The CDC anticipates that 35 million to 45 million doses of vaccines from the first two companies to receive authorization will be available in the United States by the end of this year. The current front runners are Pfizer Inc and Moderna Inc.

Drugmakers have been more ambitious with their calculations. AstraZeneca Plc has said it could deliver as many as 300 million doses of its experimental vaccine in the United States by as early as October. Pfizer and German partner BioNTech SE have said they expect to have 100 million doses available worldwide by the end of 2020, but did not specify how much of that was earmarked for the United States. Moderna on Friday said it is on track to make around 20 million doses by the end of the year and between 500 million and 1 billion doses a year beginning in 2021.

Obtaining enough doses to inoculate everyone in the United States will likely take until later in 2021. CDC Director Robert Redfield told a congressional hearing on Wednesday that vaccines may not be widely available to everyone in the United States until the second or third quarter of next year.

WHO WOULD GET AN APPROVED VACCINE FIRST?

The CDC decision will likely broadly follow recommendations from the National Academies of Sciences, Engineering and Medicine. The CDC has said the earliest inoculations may go to healthcare workers, people at increased risk for severe COVID-19, and essential workers.

It is unclear when a vaccine will be available for children as major drugmakers have yet to include them in late-stage trials. Pfizer and BioNTech have filed with regulators seeking to start recruiting volunteers as young as 16 for vaccine studies.

WHICH COMPANIES WILL LIKELY ROLL OUT A VACCINE QUICKLY?

Pfizer has said it could have compelling evidence that its vaccine works by the end of October. Moderna says it could have similar evidence in November. The vaccines would first need to be approved or authorized for emergency use by U.S. regulators.

Drugmakers have already started manufacturing supplies of their vaccine candidates to be ready as soon as they get the go ahead. The U.S. Department of Defense and the CDC plan to start distribution of vaccines within 24 hours of regulatory authorization.

Several drugmakers including Pfizer, AstraZeneca, Johnson & Johnson and Novavax Inc have all said they expect to produce at least 1 billion doses of their vaccines next year if they get regulatory authorization.

Sanofi SA and GlaxoSmithKline Plc are also working on developing a vaccine they say could be authorized next year.

(Reporting by Carl O’Donnell and Michael Erman in New York; additional reporting by Caroline Humer; editing by Peter Henderson and Bill Berkrot)

Delivering super-cooled COVID-19 vaccine a daunting challenge for some countries

By Matthias Inverardi and Ludwig Burger

FRANKFURT (Reuters) – Getting a coronavirus vaccine from manufacturing sites to some parts of the world with rural populations and unreliable electricity supply will be an immense challenge, given the need to store some vials at temperatures as low as minus 80 degrees Celsius (-112 Fahrenheit), Deutsche Post warned on Tuesday.

The German logistics firm said that distribution of an eventual vaccine across large parts of Africa, South America and Asia would require extraordinary measures to keep deliveries of so-called mRNA vaccines refrigerated at Antarctic-level temperatures.

Companies developing vaccines requiring exceptional cold storage, such as Moderna and CureVac, are working hard to make their injections last longer in transit.

The novel class of mRNA vaccines is among the furthest advanced in a field of 33 immunization shots currently being tested on humans globally, but they may need to be cooled at minus 80 degrees Celsius.

But upgrading cold storage infrastructure in regions outside the 25 most advanced countries, home to one third of the global population, will pose an immense challenge, said Deutsche Post in its study, conducted with consultancy firm McKinsey.

Vaccine developers Translate Bio and Moderna said in June they are working to produce evidence in time for the roll-out that their respective products can be shipped and stored at less extreme temperatures.

A spokesman for CureVac said its vaccine candidate is based on an experimental rabies vaccine which has already been shown to keep its molecular structure when stored in a regular fridge for months. Tests are underway to show the COVID-19 product has the same durability and the company is confident the data will be “competitive”, he added.

Deutsche Post said that even if the vaccine cold chain requires temperatures of only minus 8 degrees Celsius the share of the world’s population with reliable access to it increases only to about 70%, with substantial parts of Africa at risk of missing out.

“We anticipate 10 billion vaccine doses will have to be distributed across the world, and that includes regions that don’t have motorway access every five miles,” Katja Busch, Chief Commercial Officer of Deutsche Post’s DHL global forwarding unit, told Reuters.

(Additional reporting by Lisa Baertlein, editing by Louise Heavens)