Economics In Space

One of the most common definitions of economics is the study of the allocation of limited resources: how we use what we have, what we value, and why. There have been plenty of studies done on how economics works on earth. But what about in space?

We talk to NASA astronaut Doug "Wheels" Wheelock, who explains how the principles of economics guided trades of goods and services on the International Space Station. He also describes how his experiences changed how he values things often taken for granted on Earth, like birds, wind, and the rain.

NPR
THE INDICATOR FROM PLANET MONEY

January 21, 20215:31 PM ET

STACEY VANEK SMITH

CARDIFF GARCIA

NASA/Getty Images

CAPITALI$M IN SPACE

1st Private Crew Will Visit Space Station. The Price Tag: $55 Million Each

January 27, 202112:38 PM ET
BILL CHAPPELLTwitter


The first private excursion to the International Space Station includes a crew of former NASA astronaut Michael López-Alegría (from left) along with Canadian Mark Pathy, American Larry Connor and Israeli Eytan Stibbe.Axiom Space

A crew of private astronauts will pay around $55 million each to spend about eight days at the International Space Station next January in what would be a new step for joint private-public space missions. Axiom Space, a Houston company, says the trip will be led by former NASA astronaut and space station commander Michael López-Alegría.

The proposed Ax-1 mission will use a SpaceX rocket to put three paying customers — American Larry Connor, Canadian Mark Pathy and Israeli Eytan Stibbe – into low-Earth orbit on the space station. All of the trio are wealthy entrepreneurs and investors. The group will be under the command of López-Alegría, who is now an executive at Axiom.

It would be the first time an entirely private mission sends astronauts to the International Space Station. Russia sold the first ride to the station to a private citizen, American businessman Dennis Tito, in 2001.

All of the private astronauts for the upcoming mission are far older than the average NASA astronaut's age of 34. The space agency does not have age restrictions for astronaut candidates, who generally range from 26 to 46 years old. At 70, Connor is surpassed in age only by John Glenn, who flew on the space shuttle when he was 77.

Under NASA's rules for private astronaut missions, Axiom must ensure its astronauts meet the space agency's medical standards. They must also undergo training and certification procedures required for crew members of the International Space Station.

While the paying customers represent a new era of space tourism, they will also perform research as the space station whizzes over the Earth.

Connor will work with the Mayo Clinic and Cleveland Clinic on research projects, Axiom says, while Pathy will collaborate with the Canadian Space Agency and the Montreal Children's Hospital. Stibbe plans to do experiments for Israeli researchers, working with the Ramon Foundation and Israel's space agency.

"We sought to put together a crew for this historic mission that had demonstrated a lifelong commitment to improving the lives of the people on Earth, and I'm glad to say we've done that with this group," Axiom Space President and CEO Michael Suffredini said as the company announced the crew.

Similar missions are planned for the future, Suffredini said. Axiom hopes to arrange up to two trips per year — and the company also wants to build its own privately funded space station. Under that plan, its modules would be attached to the space station as soon as 2024. And when the space station is retired, the Axiom modules would break off to continue in orbit on their own.

NASA announced its plans to open the International Space Station to commercial activities in June 2019, saying it wants businesses to use innovation and ingenuity to speed up development of "a thriving commercial economy in low-Earth orbit."

The space agency has a plan to recoup the steep costs of a private citizen visiting the space station. Its pricing policy lists expenses such as a daily fee of $11,250 per person for "regenerative life support and toilet" and $22,500 per person for crew supplies such as food and air. The price sheet also includes a data plan, priced at $50 per gigabyte.

FACT CHECK

Pfizer and Moderna haven't proven their COVID-19 vaccines shield against new variants: analysts

by Arlene Weintraub |
Jan 28, 2021 

One infectious disease specialist said efforts to determine if existing vaccines will work against new COVID strains have left us "in a state of ignorance" due to incomplete data.

(Bill Oxford/Getty Images)

Just as the U.S. government is starting to ramp up purchases of Pfizer’s and Moderna’s mRNA vaccines to prevent COVID-19, a troubling question is emerging in the scientific community: Can these shots protect people against aggressive new variants racing through the U.K., South Africa and Brazil?

Several analysts have scoured the medical literature and interviewed infectious disease experts in an effort to answer that question. Their conclusion? There is no clear answer. At least not yet.

When it comes to SARS-CoV-2, the virus at the heart of the pandemic, “we are in a state of ignorance with incomplete data,” said SVB Leerink analyst Geoffrey Porges in a note to clients Wednesday. He reached that conclusion after interviewing an infectious disease specialist who is also an official with the FDA, he said.

Both Moderna and Pfizer have undertaken studies to try to understand how their vaccines affect the emerging variants. But they’ve taken different approaches, causing some confusion.

For example, Moderna analyzed the South African variant and found its vaccine produced sixfold fewer neutralizing antibodies against that strain than it did against the original virus. Then Pfizer followed with an analysis suggesting its vaccine was only slightly less effective against the South African strain.

Problem is, Pfizer’s analysis did not include all the mutations found in the South African variant of SARS-CoV-2, said Evercore ISI analyst Umer Raffat in a Wednesday note. In fact, it didn’t include a certain mutation that’s known to be problematic, he said. Therefore, because “the simultaneous co-mutations is where the neutralization activity starts to dip,” Pfizer’s analysis may not be entirely comprehensive, he said.

RELATED: Moderna to test different booster shot against South Africa coronavirus variant

In a separate note from SVB Leerink on Thursday, analysts pointed out vaccine makers have been testing their shots against new variants using assays that “are not validated to predict vaccine efficacy.” Typically, they’re isolating antibodies from people who received the vaccines and then testing them against “pseudoviruses” that have a single mutation from a new variant of the coronavirus.

Furthermore, it’s possible the immune system’s T cells could still mount a response against the mutant COVID strains, because they may respond to different types of protein fragments than the antibodies recognize, the analysts said. But this phenomenon has not been fully studied, therefore it’s impossible to quantify the contribution of T cells to the immune response, they wrote.

Moderna isn’t taking any chances with the emerging coronavirus variants, though. It has moved a booster vaccine that addresses the South African variant into preclinical studies and a phase 1 human trial, the company announced Monday. “As we seek to defeat the COVID-19 virus, which has created a worldwide pandemic, we believe it is imperative to be proactive as the virus evolves,” said CEO Stéphane Bancel, in a statement.

RELATED: Order up: U.S. calls on Pfizer, Moderna for 200 million more vaccine doses

Tuesday, Pfizer and its mRNA vaccine partner BioNTech followed suit, confirming they’re also working on booster shots that shield against the new COVID variants.

One advantage of the mRNA technology behind the Moderna and Pfizer products is that it allows for new vaccine constructs to be rolled out quickly, SVB Leerink’s Porges said. The FDA official he interviewed “confirmed that the development of ‘next generation’ vaccines containing the novel variant sequences could be very fast using the established platforms, potentially requiring only a ‘few hundred’ subjects that could be enrolled, vaccinated, and studied ‘in a matter of weeks.’”

Meanwhile President Joe Biden’s administration is doing everything it can to speed up the pace of vaccinations. The government is negotiating with both Pfizer and Moderna to order an additional 200 million COVID-19 vaccine doses for delivery in the third quarter. That would bring the total number of doses available in the U.S. to 600 million.

Sanofi, after R&D setback, lends a hand to vaccine rival Pfizer for coronavirus shot production

by Eric Sagonowsky |
Jan 26, 2021 

Sanofi is teaming up with Pfizer and BioNTech to help produce mRNA coronavirus vaccines. (Sanofi/Vincent Moncorgé)

Following its midstage coronavirus R&D setback, vaccine giant Sanofi is still looking for ways to help in the world’s effort to beat back the pandemic. It’s teaming up with leading vaccine players Pfizer and BioNTech to produce 100 million doses of the rival vaccine—even as Sanofi works to push its own programs through clinical testing.

After Sanofi's weak trial showing in December forced the company to delay its own vaccine development, the French drugmaker approached Pfizer and BioNTech about helping with mRNA shot production, CEO Paul Hudson said in an interview with Le Figaro newspaper.

A Sanofi spokesman confirmed the manufacturing partnership, saying Sanofi will provide BioNTech “access to our established infrastructure and expertise to produce over 100 million doses of COVID-19 vaccine in Europe in 2021.” The first batches will be delivered from Sanofi’s site in Frankfurt, Germany, by August, he said.

“While our utmost priority remains to advance our two COVID-19 vaccine programs, we recognize that some companies are facing challenges with their production,” he said. “Therefore, where we have the right manufacturing capabilities, without compromising other essential medicines and vaccines, and where we believe we can make a difference, we are stepping forward to do more for the fight against COVID and show solidarity across the industry.”

The company sees the partnership as “feasible” from a “technological and from a timing perspective,” he added.

RELATED: Weak clinical data force Sanofi, GSK to delay COVID-19 vaccine

The news comes after Sanofi’s December disclosure that lackluster phase 1/2 data had forced the company and its adjuvant partner, GlaxoSmithKline, to delay their COVID-19 vaccine development. With the setback, the company pushed its anticipated launch to late 2021 rather than the middle of 2021 as originally expected.

Now, the partners are gearing up for a phase 2b study set to begin next month; investigators anticipate including a comparison against an existing authorized vaccine in the trial, according to Sanofi’s website. Earlier in the pandemic, the company teamed up with GSK to utilize that vaccine rival's adjuvant technology.

Aside from Sanofi’s GSK-partnered vaccine, the company has an mRNA vaccine in the pipeline through its partnership with Translate Bio. That vaccine has shown early promise in preclinical trials.

RELATED: COVID-19 mRNA vaccine candidate from Sanofi and Translate protects mice, monkeys: study

The Sanofi tie-up comes as mRNA partners Pfizer and BioNTech work to scale up production to 2 billion global doses in 2021. Amid that push, the companies temporarily reduced shipments to Europe this month, causing some countries to push back at the move. Meanwhile, AstraZeneca has suffered a manufacturing issue that will force it to reduce first-quarter deliveries to Europe.

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AstraZeneca, EU officials duke it out in the press as COVID-19 vaccine supply battle heats up

by Eric Sagonowsky |
Jan 27, 2021 

AstraZeneca CEO Pascal Soriot said the company's EU coronavirus vaccine supply deal carries no legal obligation to deliver doses on a specific timeline. (AstraZeneca)


Within days of AstraZeneca's surprise cut to first-quarter COVID-19 vaccine deliveries to Europe, a fierce debate between the drugmaker and government officials is playing out behind the scenes—and in the press.

CEO Pascal Soriot said the company has no legal obligation to deliver vaccines on a specific timeline. The EU maintains AZ’s new delivery schedule is “not acceptable.”

The sides were set to meet Wednesday, but an EU official told Politico the drugmaker had pulled out. AstraZeneca told Fierce Pharma via email it hadn't.

The back-and-forth comes as both sides seek to manage public opinion while salvaging their own relationship and getting deliveries back on track—and after AstraZeneca disclosed last week that a manufacturing problem would force a big reduction in Q1 supplies.

The company was originally set to deliver 80 million doses to Europe in the first quarter, but that number has been reduced to 31 million, according to Reuters. A spokesperson last week told Fierce Pharma the company plans to deliver "tens of millions" of doses to Europe in February and March.

In a statement Monday, European Commissioner for Health and Food Safety Stella Kyriakides said the EU "pre-financed the development of the vaccine and the production and wants to see the return." She wrote a letter to the company raising "important and serious" questions, she added.

RELATED: AstraZeneca's surprise COVID-19 vaccine shortfall prompts Europe to press for answers

Meanwhile, Soriot told AstraZeneca's side of the story in an interview this week with Italian newspaper la Repubblica. The company isn’t contractually obligated to deliver doses on a specific timeline under its EU agreement, he said. Rather, the deal called for AZ to make its “best effort” to deliver on its promise.

OK, then, EU officials said after the interview, AstraZeneca should publicly release its contracts, Reuters reports. An EU official told the news service that the details Soriot disclosed were supposed to be confidential and the “best effort” clause was standard for agreements centering on products that don’t yet exist.

Soriot also said AstraZeneca owed the U.K. first. Britain finalized its deal with AstraZeneca three months before the European Union struck its own, Soriot added, giving AZ a “head start” to work through potential manufacturing issues in that supply chain. Soriot has rejected calls to divert U.K. doses to Europe, The Guardian reports.

The source of the trouble in Europe is a Novasep factory in Belgium the Wall Street Journal reported, citing sources. The facility has only been able to turn out about a third of the yield AZ had been expecting, the Journal said. Meanwhile, in the U.K., AstraZeneca has partnered with at least one local manufacturer, Wockhardt, which is turning out doses at a plant in Wales.

"Governments are under pressure,” Soriot told the la Repubblica newspaper. “Everybody is getting kind of a bit, you know, aggravated or emotional about those things. But I understand because the Commission is managing the process for the whole of Europe.”

RELATED: Sorry, Europe: AstraZeneca follows Pfizer/BioNTech in cutting back EU vaccine delivery plans

AZ told Reuters in a statement that its COVID-19 vaccine supply chains were set up around individual agreements with countries or international organizations. Vaccines produced under the deals are "dedicated to the relevant countries or regions" and the deals rely on "local manufacturing wherever possible," the company said.

As if to support that argument, Serum Institute of India said its manufacturing is on track; it's set to supply multiple countries with vaccines, including its home country, Brazil and Saudi Arabia. Overall, AstraZeneca has set up deals with 20 different manufacturing partners around the world.

As AstraZeneca works through its manufacturing issues, the mRNA vaccine team of Pfizer and BioNTech are working to scale up their global supply chain—an effort that caused a temporary glitch in European and Canadian deliveries.

But on Tuesday, vaccine giant Sanofi said it's also stepping in to help. After the company's own vaccine took a hit in phase 2 testing, Sanofi approached Pfizer and BioNTech about a manufacturing partnership. Sanofi is now set to produce 100 million doses of the Pfizer/BioNTech mRNA vaccine for Europe this year.

Novartis says it's ready to pitch in on manufacturing rivals' COVID-19 vaccines, diagnostics

by Eric Sagonowsky |
Jan 28, 2021 9:57am

Novartis is looking into manufacturing partnerships to boost coronavirus vaccine and diagnostic supplies, a spokesman said. (Novartis)

Right after Sanofi stepped in to help produce Pfizer/BioNTech coronavirus vaccines in Europe, Novartis is exploring whether it can deploy its own manufacturing network to boost COVID-19 supplies. Separately, the U.S. is weighing the Defense Production Act to compel drugmakers to produce Pfizer or Moderna mRNA vaccines.

Novartis is "currently in discussions with several companies with a view to supporting the manufacturing of vaccines and components for tests for Covid-19," a spokesman said.

Novartis sees controlling the pandemic as "one of the most pressing concerns for leaders, businesses and individuals all across the world," he said, so the company is "exploring ways in which we can collaborate with our partners in the industry, and leverage our manufacturing capacity and capabilities to contribute to the pandemic effort."

Though Novartis isn't at the forefront of COVID-19 vaccine or drug development, it is involved in the fight. Last year, Novartis' gene therapy outfit AveXis signed up to produce an early-stage COVID-19 gene therapy being investigated by researchers at Massachusetts General Hospital and Massachusetts Eye and Ear, for instance.

Meanwhile, the U.S. government is considering tapping drug manufacturers who aren’t already making vaccines to produce doses of either the Pfizer or Moderna mRNA shots via the Defense Production Act, Reuters reports. Both vaccines carry FDA emergency authorizations, but limited supply and logistics hurdles have complicated their rollouts.

RELATED: Sanofi, after R&D setback, lends a hand to vaccine rival Pfizer for coronavirus shot production

At a media briefing this week, White House senior COVID-19 advisor Andy Slavitt said he didn’t want to “talk about specific names," as quoted by the news service, but he said the administration is “not afraid to explore every option to get more vaccines to the public as quickly as possible." Before taking office, President Joe Biden’s advisors said the new president would invoke the Defense Production Act to boost vaccine supplies.

The talks come right after the French drugmaker Sanofi signed up to produce 100 million doses of the Pfizer/BioNTech vaccine for Europe. After Sanofi late last year suffered an R&D setback for its own vaccine program, the company reached out to rival Pfizer to see if it could help with manufacturing. The first batches will be delivered from Sanofi’s site in Frankfurt, Germany, by August, a spokesman said.

Even as the Biden team considers the Defense Production Act, experts recently raised concerns to Kaiser Health News about the legality of the plan and complexity of mRNA vaccine production. Converting an existing pharma manufacturing plant would require significant time, rigorous cleaning, converting equipment and training staff, they said. Plus, there’s no way to be sure vaccines that come from the new plant are safe and effective without testing, one expert told KHN.

RELATED: Order up: U.S. calls on Pfizer, Moderna for 200 million more vaccine doses

In a separate move to address supply concerns, the Biden administration this week ordered another 200 million mRNA vaccine doses from Pfizer and Moderna, taking the U.S. total haul up to 600 million doses. That supply, when it’s delivered, will be enough to vaccinate 300 million people, or almost the entire U.S. population. The new doses are on tap to be delivered this summer.

The administration is also weighing bringing more distributors on board to bolster deliveries, Reuters reports.

PANDEMIC PROFITEERING

Pfizer – Consensus Indicates Potential 11.5% Upside

• Charlotte Edwards
• January 28, 2021
• 
  

Pfizer with ticker code (PFE) now have 20 analysts covering the stock with the consensus suggesting a rating of ‘Hold’. The target price ranges between 53 and 36 and has a mean target at 41.59. Now with the previous closing price of 37.31 this would indicate that there is a potential upside of 11.5%. The day 50 moving average is 37.76 and the 200 moving average now moves to 36.18. The company has a market capitalisation of $202,215m. Visit the company website at: http://www.pfizer.com

Pfizer Inc. develops, manufactures, and sells healthcare products worldwide. It offers medicines and vaccines in various therapeutic areas, including cardiovascular metabolic and pain under the Eliquis, Chantix/Champix, and Premarin family brands; biologics, small molecules, immunotherapies, and biosimilars under the Ibrance, Sutent, Xtandi, Xalkori, Inlyta, Braftovi + Mektovi brands; and sterile injectable and anti-infective medicines under the Sulperazon, Medrol, Vfend, and Zithromax brands. The company also provides medicines and vaccines in various therapeutic areas, such as pneumococcal disease, meningococcal disease, and tick-borne encephalitis under the Prevnar 13/Prevenar 13 (pediatric/adult), FSME-IMMUN, Nimenrix, and Trumenba brands; biosimilars for chronic immune and inflammatory diseases under the Xeljanz, Enbrel, Inflectra, and Eucrisa brands; and amyloidosis, hemophilia, and endocrine diseases under the Vyndaqel/Vyndamax, BeneFIX, Genotropin, and Refacto AF/Xyntha brands. In addition, the company is involved in the contract manufacturing business. It serves wholesalers, retailers, hospitals, clinics, government agencies, pharmacies, and individual provider offices, as well as disease control and prevention centers. The company has collaboration agreements with Bristol-Myers Squibb Company, Astellas Pharma US, and Myovant Sciences Ltd.; a licensing agreement with Akcea Therapeutics, Inc; a strategic alliance with Verily Life Sciences LLC; collaboration agreements with Merck KGaA and Valneva SE; a clinical trial collaboration and supply agreement with IDEAYA Biosciences; collaboration agreement with BioNTech SE; a clinical supply collaboration with Jiangsu Alphamab Biopharmaceuticals Co., Ltd; a research collaboration and license agreement with BioInvent International AB; a drug discovery collaboration with Sosei Group Corporation; and collaboration with LianBio. Pfizer Inc. was founded in 1849 and is headquartered in New York, New York.

Pfizer - Consensus Indicates Potential 11.5% Upside - DirectorsTalk Interviews

PUBLIC OWNERSHIP OF BIG PHARMA

COVID vaccine supply is causing an EU crisis –

so what’s being done to speed up production?

January 28, 2021

The EU has a vaccine shortage problem. AstraZeneca pledged earlier this month to supply 2 million doses a week to the UK, but has also said it will cut deliveries to the EU from 80 million doses to 31 million during the first quarter of 2021.

The UK has vaccinated more than 11% of its population so far. EU nations such as Italy, Poland, Finland and Germany have only vaccinated between 2% and 3%. After the tense Brexit negotiations and the criticism the UK received for not joining the EU vaccine procurement scheme, this difference is stark. The EU, understandably, is keen not to fall further behind in rolling out vaccines and so has demanded it be given doses of the AstraZeneca vaccine made in the UK.

Whether the EU’s contract with AstraZeneca is a commitment to deliver certain quantities or an agreement for the company to do its “best effort” is contested. The content of the contract and timings of orders will be at the core of arguments over who should receive stock and when. The dispute continues.

This is all down to the vaccine pipeline being squeezed – but why are vaccine manufacturers struggling to keep up the pace of production? Details of the contracts between vaccine producers and the UK or the EU are not publicly available, but what is known about the vaccines’ supply chains can explain some of the reasons for the current shortage.

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Lower production output

The immediate problem stated by AstraZeneca is a lower than expected output at a manufacturing site in its European supply chain. This can happen because vaccines are complex biological products: the production process does not always yield the same amount of usable vaccine. Stringent quality checks are also in place to ensure that all batches are safe. If the quality is not right, less vaccine becomes available.

According to AstraZeneca chief executive Pascal Soriot, issues with yield are to be expected when rapidly increasing production. He says that such problems have also occurred in plants in Australia, the US and the UK. However, as the UK signed its contract three months earlier than the EU, there was more time to resolve any teething issues.

Issues can interrupt operations too. Vaccine production at an AstraZeneca site in Wales had to be paused for several hours while a suspect package was investigated. And in India, a fire at the Serum Institute (the world’s largest vaccine producer, which has a licence to produce the Oxford/AstraZeneca vaccine) claimed several lives, but reportedly did not affect production

.

Despite the fire, India’s Serum Institute is aiming to manufacture 1 billion vaccine doses in 2021. EPA-EFE

To deliver billions of vaccines to the world, production capacity has to be large – but increasing it can lead to delays as well. Pfizer announced a temporary decrease in output in order to expand a Belgian factory, for example. The Belgian plant is the core supplier of Pfizer/BioNTech vaccines for Canada, the EU and the UK, which shows how widespread knock-on effects can be.

How to safeguard production

One way around this problem is to increase capacity by working with competitors. For instance, the French pharmaceuticals company Sanofi has announced that it will produce more than 100 million doses of the Pfizer/BioNtech vaccine. This puts Sanofi’s existing production capacity to use even though its own COVID-19 vaccines are experiencing delays. Such “coopetition” – simultaneous competition and cooperation – is not unusual in supply chains.

Another way to bolster production is to use regional supply chains to make and distribute vaccines, with each serving only particular parts of the world. Not relying on just one supply chain enhances overall resilience; if something goes wrong in one supply chain, the others can still function. Spreading production around the world – which is what AstraZeneca has done – also means easier access to appropriate facilities and trained staff.

However, this strategy is now at the heart of the disagreement with the EU. The EU is suggesting that the shortfall in yield at a Belgian AstraZeneca plant should be made up by distributing doses produced in the UK. But that would mean an inability to fulfil contractual obligations to Britain.

EU health commissioner Stella Kyriakides to AstraZeneca: ‘We reject the logic of first come, first served.’ Alexandros Michailidis/Shutterstock

To avoid these sorts of issues, other countries are keen to set up their own vaccine production sites. Australia has announced it has paid a premium to produce the AstraZeneca vaccine domestically. From March, its output is expected to be around 1 million doses per week.

But domestic production is also not without its problems. Brazil plans to rely mainly on domestic production and has a strong pharmaceutical industry to support this. But it needs to import key ingredients, a process that is currently hampered by bureaucratic hurdles and technical issues. It will still rely on supply chains elsewhere – particularly in India and China.

The cost of ‘vaccine nationalism’

At the moment, demand for COVID-19 vaccines is much higher than supply. Competition to secure doses is fierce, with many disappointed parties demanding answers – when the vaccines will arrive and in what quantity. Uncertainty may lead to vaccine protectionism, with stock produced in key locations withheld and hoarded to serve only local populations.

But while rich countries’ concerns about delayed deliveries are valid, it’s important to keep in mind that many nations will not have widespread access to vaccines in 2021. Concern about the lack of equal access to medicines has been voiced globally, nationally and regionally, as government bodies attempt to secure vaccines for their populations.

Developed nations focusing on themselves is not going to help solve a global crisis. As long as the virus is free to spread and mutate in some countries, no country is safe. The global economy could lose more than US$9 trillion (£6.6 trillion) if governments fail to ensure developing economies have access to COVID-19 vaccines. This vast figure points to the dangers of these current moves towards self-interest.

Authors
Liz Breen

Senior Lecturer in Supply Chain Management, Liverpool John Moores University

 

Sarah Schiffling

Director of the Digital Health Enterprise Zone (DHEZ), University of Bradford, Reader in Health Service Operations, University of Bradford

(C)REALSCIENCE  

SARS-CoV-2 Vaccines and the Growing Threat of Viral Variants
John P. Moore, PhD1; Paul A. Offit, MD2

Author Affiliations Article Information
JAMA. Published online January 28, 2021. doi:10.1001/jama.2021.1114

Audio Clinical Review (40:57)
Understanding SARS-CoV-2 Genetic Variants
  
Conversations with Dr Bauchner (43:00)
Coronavirus Vaccine Update with Paul Offit and Robert Wachter
  
Video (44:16)
Coronavirus Vaccine Update With Paul Offit and Robert Wachter


In November 2019, a bat coronavirus made its debut in the human population. Since that time, the virus has continued to adapt, resulting in a series of viral variants. The question that the world faces in early 2021 is whether these new variants will escape recognition by vaccine-induced immunity.

Protection against coronavirus disease 2019 (COVID-19) is mediated in large part by an immune response directed against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S)-protein. The S-protein is responsible for virus-cell binding and is the target for virus-neutralizing antibodies (NAbs). Although this is not strictly proven, most vaccine researchers believe that NAbs induced by vaccination are protective against COVID-19. NAbs bind to the S-protein at a few sites, usually in or near the receptor-binding domain (RBD); in doing so, NAbs prevent the virus from attaching to the ACE2 receptor on human cells.

Variants in the S-protein that increase the amount of virus shed from an infected person or that increase its affinity for the ACE2 receptor are likely to increase virus transmission, an important problem in the context of a pandemic. Furthermore, the same or similar alterations can change the shape of the S-protein and impair or even destroy NAb binding sites. Hence, by extrapolation, vaccine efficacy might be compromised. These “escape mutations” typically arise when the virus is put under selective pressure by antibodies that limit but do not eliminate viral replication. Under these conditions, the virus might then find a way to escape this pressure and restore its ability to reproduce more efficiently. The scenario of virus evolution in the face of suboptimal immunity is one reason extending the interval between the first and second dose of a SARS-CoV-2 vaccine might be problematic.

Evolutionary biology is now occurring across the globe. The first major shift in the properties of SARS-CoV-2 took place early in the pandemic—around March and April 2020—when the original strain was replaced worldwide by a new variant called D614G.1 The relevant mutation in this variant, which is located in the S-protein, has been shown to increase the replication efficiency and transmissibility of the virus.2 Although this variant did not escape recognition by NAbs, it was a warning of what could happen.

In August 2020 another variant started to spread in the UK (where surveillance for such events is particularly thorough), and its contribution to the pandemic in that country increased rapidly from November 2020 through January 2021. Often called the “UK strain,” but more formally known as B.1.1.7, this variant has now been detected in many countries, including the US. The key sequence change in the S-protein is called N501Y, which again appears to increase the transmissibility of SARS-CoV-2, although in a manner subtly different from D614G. Regarding protection by vaccination, however, again fortunately, the location of the N501Y change makes it unlikely to affect most of the NAb binding sites on the RBD.3 For example, recently released data show that serum samples from the recipients of the Pfizer-BioNTech and Moderna mRNA vaccines are equally effective at neutralizing viruses that contain or lack the N501Y change.4,5

A more transmissible variant now circulating in southern California, CAL.20C, has an RBD sequence change called L452Y that is thought to act similarly to N501Y.6 Its sensitivity to vaccine sera remains to be determined.

There is now, however, a more troubling new variant identified in South Africa, the N501Y.V2 variant (or B.1.351). A close relative to N501Y.V2 with similar properties has now also been identified in Brazil (P.1), but much less is known about this variant. The N501Y.V2 strain has many more sequence changes than both the D614G and B.1.1.7 variants, and those sequence changes are more worrisome because they are located in or close to the RBD; these sequence changes also affect another NAb target, the N-terminal domain.

The number and positioning of these mutations immediately raised concerns among vaccine researchers. New data show that those concerns were not misplaced. Rockefeller University researchers have shown that the relevant N501Y.V2 sequence changes within the RBD modestly reduce the efficiency with which mRNA vaccine-induced antibodies neutralize test viruses in the laboratory.7 In addition, a National Institutes of Health study now shows that NAbs induced by the Moderna mRNA vaccine are about 6-fold less active against the N501Y.V2 (B1.351) strain.5

It remains unclear whether the reduction in the neutralization sensitivity of the N501Y.V2 strain to vaccine-induced antibodies is enough to seriously reduce vaccine efficacy. First, mRNA vaccines also induce virus-specific helper T cells and cytotoxic T cells, both of which might be involved in protection against challenge. Also, the mRNA vaccines, in particular, induce such a strong NAb response that there could be enough “spare capacity” to deal with reductions in the sensitivity of the variant to NAbs. In other words, N501Y.V2 (and the related virus from Brazil) may be less sensitive to NAbs, but not to an extent that will cause widespread vaccine failure. However, vaccines that appear to induce lower levels of NAbs, such as the inactivated vaccines developed in China and India, may be less effective. It is too early to know how the replication-defective simian or human adenovirus vector-vaccines (Johnson & Johnson/Janssen’s, AstraZeneca’s, and the Russian “Sputnik V”) or the adjuvanted purified protein vaccines (Novavax and Sanofi/GSK) might be affected. Much work is now being performed worldwide to better understand how these different vaccines are affected by the N501Y.V2 and related variants. An important clue should emerge when several phase 3 vaccine efficacy trials now ongoing in South Africa are completed. Will the increasing dominance of N501Y.V2 in that country affect how well these vaccines protect the trial participants? Time will tell.

In addition to avoiding recognition by vaccine-induced immunity, variants have also become less susceptible to neutralizing monoclonal antibodies (nMAbs). The N501Y change in the B.1.1.7 variant, for example, is sufficient to almost ablate the activity of several nMAbs, and the South African team’s study shows that almost all of the nMAbs tested against N501Y.V2 were now ineffective.8 The nMAbs that are approved by the Food and Drug Administration to treat SARS-CoV-2 infection need to be carefully assessed against all these new variants.

Given the rise of these viral variants, several steps should be taken.

First, SARS-CoV-2 viruses must be immediately isolated and characterized from individuals who have been fully vaccinated but are nonetheless admitted to the hospital with COVID-19. This would likely be the first sign that variant viruses are becoming resistant to vaccine-induced immunity.

Second, the US should create and maintain an active sequencing and surveillance system to identify these variants quickly once they arise. While the UK has been excellent in this regard, the US and much of the rest of the world has not. International cooperation is essential to do this properly.

Third, it would be of value to create a central repository of serum samples from people in the US who have been immunized with SARS-CoV-2 vaccines. This resource would enable researchers to test their neutralizing capacities against any new variants as soon as they are identified. In this way, it will not be necessary to depend on pharmaceutical companies, who have limited quantities of serum samples generated from phase 3 trials, to do these studies. A central repository should include samples representing all the approved vaccines, as well as those still in phase 3 trials, to enable gauging both the depth and breadth of neutralization resistance.

Fourth, it is essential to reduce the global spread of new variants, particularly N501Y.V2 and its related Brazilian variant. While it is likely that these viruses are already present in the US, the more often they are reintroduced, the more likely they will make it into a superspreader event, with very serious consequences for wider spread.9

Fifth, the designs of the mRNA and replication-defective adenovirus vaccines can be adjusted to accommodate the key sequence changes present in the new variants. The initial stages of this process are fairly straightforward and can be accomplished rapidly.

Sixth, like those that have circulated throughout 2020, the new variants are not spread by aerosolization in a manner similar to measles virus nor do they travel long distances. Wearing masks, physical distancing, and applying common sense can prevent their spread.

Corresponding Author: Paul A. Offit, MD, Division of Infectious Diseases, Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, 34th St & Civic Center Blvd, ARB, Room 1202C, Philadelphia, PA 19104-4399 (offit@email.chop.edu).

Published Online: January 28, 2021. doi:10.1001/jama.2021.1114

Conflict of Interest Disclosures: None reported.

Editor’s Note: Although preprints are rarely included as references in JAMA articles, in the midst of the COVID-19 pandemic some of the information in this article is based on rapidly developing and emerging science that is only available as preliminary communications on preprint servers.
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DOJ should investigate social media platform Gab and its CEO over Capitol riots, according to anti-hate group

Nathan Bomey
USA TODAY


A national anti-hate group is calling for the Department of Justice and the FBI to investigate a conservative social media company and its CEO over allegations that they may have "intentionally aided, conspired with or directed" rioters who attacked the U.S. Capitol 

on Jan. 6.

The Anti-Defamation League released an open letter Wednesday morning calling for authorities to investigate Gab and its CEO, Andrew Torba, saying they "may well bear a measure of criminal responsibility for the attack."

The move comes amid growing pressure on social media outlets that serve as a petri dish for hate and violence. In recent days, Apple, Google and Amazon have taken action to strip conservative social media outlet Parler of its distribution platforms amid accusations that rioters planned aspects of their attack on its platform. Parler has said it is committed to removing content calling for violence.

Gab gains momentum

Although still a niche outlet, Gab has been gaining momentum since the election amid false allegations of fraud as President Donald Trump continues to claim that he won the election. When Trump incited his supporters to march on the Capitol on Jan. 6, they took action by bashing into the building.

The ADL cited a report that Gab commenters exchanged "directions for which streets to take to avoid the police and which tools to bring to help pry open doors," while "multiple people posted about carrying guns into the halls of Congress."

Torba himself posted to Gab on Jan. 6 that "in a system with rigged elections there are no longer any viable political solutions," according to ADL's letter.

"The phrase 'there is no political solution' is used in online accelerationist white supremacist circles to further the idea that the US government system is rotten, democratic processes for change are futile and therefore the system should be destroyed," the ADL said. "The phrase embraces political violence as the only valid response."

Gab CEO responds

The organization also reported that before the riot began, Torba posted that it “would be a real shame if the people outside stormed the Senate.”

In an emailed response to USA TODAY's request for comment, Torba called for an investigation into Facebook instead and said Gab had "put an immediate stop to a series of newly created accounts that were making threats of violence aimed at public officials" in December.

"We worked diligently with law enforcement and spent several weeks warning our community about this behavior and taking swift action to remove it from our platform," Torba said in the email. "Our moderation and legal teams work tirelessly to ensure public safety. Threats of violence and illegal activity have no place on Gab."

Gab also posted Torba's response and a screenshot of USA TODAY's emailed request for comment to Twitter.

Since the crackdown on Parler, Gab has said it has experienced a surge in users, saying it saw 40 million visits last week.

Pittsburgh synagogue shootings

Gab first launched in 2016 and has remained online despite efforts to shut it down in 2018 after it was discovered the suspected gunman in the Pittsburgh synagogue shooting that killed 11 people posted on the platform.

Gab was launched as an alternative to traditional platforms such as Twitter and Facebook. During that time, Twitter had suspended several accounts associated with extremist groups on the same day it vowed a crackdown on hate speech. The suspensions pushed many people to Gab, which has fewer content restrictions compared with Facebook, Twitter and other platforms.

"We believe that the future of online publishing is decentralized and open," reads a description on Gab's website. "We believe that users of social networks should be able to control their social media experience on their own terms, rather than the terms set down by Big Tech."

Users turned to Gab, and also Parler, in part because of concerns that larger platforms such as Twitter were censoring conservative opinions. However, the relaxed rules opened the door for content such as conspiracy theories and misinformation.


Mob fallout: Trump-supporting Chicago CEO arrested for allegedly entering Capitol during riots

Post-election momentum:Parler, MeWe, Gab gain momentum as conservative social media alternatives