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

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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

Robinhood users are revolting against the trading app after it stopped trades of GameStop
Ben Gilbert and Allana Akhtar

Robinhood users are furious after the app stopped allowing users to buy GameStop stock on Thursday morning.

The stock-trading app was flooded with one-star reviews on the Google Play store, which lowered its user rating.

Big names like Rep. Alexandria Ocasio-Cortez, Mark Cuban, and Dave Portnoy all publicly criticized the company.

Robinhood users are coming for the trading app's head.

Vlad Tenev, the cofounder and co-CEO of the investing app Robinhood.

 REUTERS/Brendan McDermid

The trading platform stopped allowing users to buy GameStop stock on Thursday morning, allowing users to sell only, following weeks of huge gains — from being below $5 in late 2020 to over $450 per share on Thursday morning.

Users of the Reddit forum r/wallstreetbets encouraged each other to bid up GameStop's stock price, thus causing a short squeeze on the hedge funds betting against GameStop's stock value. As a result, those short sellers lost more than $1 billion in a single day, while the company's stock value jumped by hundreds of dollars per share.

On Thursday morning, Robinhood cut off users from trading GameStop stock (and a handful of other companies), citing "significant market volatility."

That decision caused a massive outcry on social media.

"Robinhood has disabled trading in $AMC $GME $NOK etc, proving that the 'little guy' was never allowed to win in a 'free market,'" the popular newsletter writer Joe Pompliano said in a tweet. "What a joke."

—Joe Pompliano (@JoePompliano) January 28, 2021

—Drew Welker (@dwelkeroutdoors) January 28, 2021

—Mike McLean (@mikemcln) January 28, 2021

The Robinhood app listing received an influx of one-star reviews on the Google Play store, causing the app to average the lowest rating.

Robinhood received an influx of one-star reviews on the Google Play store. Allana Akhtar/Business Insider

And members of Wall Street Bets threatened to file a class-action lawsuit against Robinhood, alleging market manipulation.


"Allowing people to only sell is the definition of market manipulation," one post on Wall Street Bets said. "A class action must be started, Robinhood has made plenty of money off selling info about our trades to the hedge funds to be able to pay out a little for causing people to lose money now."

Robinhood, founded in 2013 by the Stanford graduates Baiju Bhatt and Vladimir Tenev, allows users to trade stocks without commission.

"We're proud to have created a platform that has helped everyday people, from all backgrounds, shape their financial futures and invest for the long term," the firm said in a blog post.

Instead of taking commissions on stock trades, the company says it earns revenue through a variety of other means, from financial services to a membership program, Robinhood Gold.

Read more: How hedge funds are tracking Reddit posts to protect their portfolios after the Wall Street Bets crowd helped tank Melvin Capital's short positions

Users aren't the only ones criticizing Robinhood publicly.

The billionaire Mark Cuban questioned why Robinhood restricted trading, tweeting: "So are @robinhoodapp and @IBKR ending trading in #wallstreetbets stocks because they are losing their ass on these trades? Or maybe they don't have the cash to enable the trades at this scale? Anyone have any insight on their economics?"

—Mark Cuban (@mcuban) January 28, 2021

Barstool Sports, along with the blog's founder, Dave Portnoy, declared "war" on Robinhood.

"You are scam artists," Portnoy tweeted in response to Robinhood's announcement on restricting trading. "You are crooks. You deserve to be behind bars and you know it."

—Barstool Sports (@barstoolsports) January 28, 2021

Rep. Alexandria Ocasio-Cortez said Robinhood's actions were "unacceptable" and called for "a hearing if necessary" to determine why the company chose to "block retail investors from purchasing stock while hedge funds are freely able to trade the stock as they see fit."

Sen. Ted Cruz seconded Ocasio-Cortez's tweet. "Fully agree," he said.

Pulte Capital CEO Bill Pulte, a philanthropist, weighed in as well.

"This is what you call rich people trying to confuse you with fancy words," he tweeted in response to Robinhood's statement on why it was restricting stock trades of GameStop.

Robinhood representatives didn't immediately respond to a request for comment.

The wild trading surrounding GameStop, AMC, and other companies this week is even drawing attention from the White House.

Why did shares of GameStop and AMC soar?
Brett Molina
USA TODAY

It has been a wild week for GameStop.

Shares of the struggling video game retailer surged to more than $480 a share Thursday morning before plunging to just over $200 around midday, falling well below their Wednesday close of $347.51. At the start of 2021, shares of GameStop closed at $17.25 on Jan. 4.

The primary reason for the earlier surge? Smaller investors who have banded together in places like Reddit, under the subreddit r/WallStreetBets.

And it's not just GameStop. Shares of AMC Entertainment jumped more than 230% Wednesday as the Twitter trend #SaveAMC spread amid concerns the movie theater chain might file for bankruptcy due to the COVID-19 pandemic keeping moviegoers away.

Even BB Liquidating, the remains of former video rental giant BlockBuster, saw a spike in its price, reports Bloomberg.

So what is going on? Here's what you should know.

What is r/WallStreetBets?

According to a description on its subreddit, it's "like 4Chan found a Bloomberg terminal." It was created in 2012 and has 3 million followers discussing making money and trading stocks, options, futures and more.

After the news gained steam, moderators switched to an invite-only status Wednesday evening. "We are experiencing technical difficulties based on unprecedented scale as a result of the newfound interest in WSB," they said in a note on the site.

Interest in r/WallStreetBets has garnered so much attention that Bloomberg expects the Securities and Exchange Commission will have to look at issues such as these for market influence. 

How did GameStop shares jump?

Investors have been short selling the stock – borrowing shares, immediately selling them, then buying them back at a lower price before returning the shares – because of the retailer's ongoing struggles as a brick-and-mortar chain competing with consumers increasingly shopping online.

As those investors bet on GameStop's price to sink, a group of traders on Reddit have joined together to drive the retailer's stock price higher. Posts and threads from the subreddit seem to suggest this as an opportunity to stick it to Wall Street.

One Reddit post describes the surge of these stocks as "a tug of war between tradition and the future."

"Hedge fund managers live in the past, and continue to look down upon the retail investors," reads an excerpt of the post on WallStreetBets. "They truly believe that we, the average retail investors, don't know anything about finances or the market (which may be true), and we're just gambling our money away."

The movement even got the attention of Tesla CEO Elon Musk, sharing the subreddit with a tweet simply saying "Gamestonk!" The billionaire has openly shared his disdain for short sellers over wanting to see shares in Tesla decline.

Reddit said Wednesday afternoon the site is currently down for some users.

How is Wall Street responding?

Trading apps such as Robinhood, TD Ameritrade, E*Trade and Charles Schwab all appear to be suffering from outages, according to Down Detector, a website that tracks issues with online services.

These apps have contributed to a rise in investing among individuals. As the Wall Street Journal reports, individual investors accounted for nearly 20% of shares traded in the stock market, according to Bloomberg Intelligence.

In a statement obtained by USA TODAY, TD Ameritrade said it is setting restrictions on trades involving GameStop and AMC.

"In the interest of mitigating risk for our company and clients, we have put in place several restrictions on some transactions in $GME, $AMC and other securities," said the company. "We made these decisions out of an abundance of caution amid unprecedented market conditions and other factors."

According to multiple reports on Twitter and Reddit, Robinhood has halted trading on GameStop. A representative from Robinhood could not immediately be reached for comment to confirm.

Meanwhile, major investors Citron Research and Melvin Capital have both claimed they are pulling their bets on GameStop.

The Associated Press contributed to this report. Follow Brett Molina on Twitter: @brettmolina23.