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Hitting the Books: How Moderna dialed-in its vaccine to fight COVID’s variants

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Hitting the Books: How Moderna dialed-in its vaccine to fight COVID’s variants

The national news cycle may have largely moved on from coverage of the COVID-19 pandemic — despite, as of this writing, infections being on the rise and more than 300 deaths tallied daily from the disease. But that certainly doesn’t diminish the unprecedented international response effort and warp speed development of effective vaccines. 

In The Messenger: Moderna, the Vaccine, and the Business Gamble That Changed the World, veteran Wall Street Journal reporter Peter Loftus takes readers through the harrowing days of 2020 as the virus raged across the globe and biotech startup Moderna raced to create a vaccine to halt the viral rampage. The excerpt below takes place in early 2021, as the company works to adapt its treatments to slow the surging Delta variant’s spread.

Messenger Cover

Harvard Business Review Press

Reprinted by permission of Harvard Business Review Press. Excerpted from The Messenger: Moderna, the Vaccine, and the Business Gamble That Changed the World by Peter Loftus. Copyright 2022 Peter Loftus. All rights reserved.


Delta

Viruses of all types frequently change. They mutate as they jump from person to person. The coronavirus was no different. Throughout the pandemic, health officials tracked variants of the SARS CoV-2 virus first found in Wuhan, China, as those variants arose. None seemed a big concern, until one was flagged in the United Kingdom in December 2020, right as Moderna’s vaccine neared approval. This UK variant appeared to be as much as 70 percent more transmissible. It was given the name the Alpha variant.

Alpha reinforced the possibility that the virus could mutate enough to become resistant to vaccines and treatments that were designed to target the earlier, predominant strain. Or it could fizzle out. But variants would keep coming. Shortly after Alpha, researchers identified another variant circulating in South Africa. Beta.

In late December—just a few days after the United States authorized its vaccine — Moderna issued a statement that it was confident the vaccine would be effective at inducing the necessary immune response against variants. The original vaccine targeted the full length of the spike protein of the coronavirus, and the new variants appeared to have mutations in the spike protein that represented less than a 1 percent difference from the original.

“So, from what we’ve seen so far, the variants being described do not alter the ability of neutralizing antibodies elicited by vaccination to neutralize the virus,” Tal Zaks said during a virtual appearance at the all-important J.P. Morgan Healthcare Conference in January 2021. “My definition of when to get worried is either when we see real clinical data that suggest that people who’ve either been sick or have been immunized are now getting infected at significant rates with the new variants.”

Even if the vaccine proved less effective against a new variant, Moderna could use its mRNA technology to quickly tweak the design of its Covid-19 vaccine, to better target a variant of the virus, Zaks said. After all, the company and its federal health partners had already demonstrated the year before how quickly they could design, manufacture, and test a new vaccine.

Still, Moderna needed to run a series of tests to see if its original vaccine offered the same high level of protection against variants as it showed in the big Phase 3 clinical trial.

Moderna collaborated again with researchers from NIAID including Barney Graham and Kizzmekia Corbett. They analyzed blood samples taken from eight people who were vaccinated with Moderna’s shot in the Phase 1 trial back in early 2020. They essentially mixed these blood samples with the coronavirus variants, engineered so they copied the mutations of the variants but couldn’t replicate and pose a threat to lab researchers. Researchers then analyzed whether the vaccine-induced antibodies present in the human blood samples could effectively neutralize the virus variants.

The results were mixed. They suggested the vaccine worked as well against the UK Alpha variant as against the original strain of the coronavirus. That was good news. Even if the UK variant spread more easily than the original virus, Moderna’s vaccine could probably mute its effects.

But the Beta variant first identified in South Africa seemed to pose a problem. The vaccine-induced antibodies had a significantly reduced neutralization effect on this strain in the lab tests. “Oh shit,” Bancel said when Stephen Hoge showed him the data. It wouldn’t be the last time. Moderna’s leaders saw the data on a Friday in late January 2021 and spent the weekend discussing it. They hoped that a modified, variant- targeted vaccine wouldn’t be needed, and that Moderna’s original vaccine would suffice, even if it had a reduced neutralizing effect. But Moderna didn’t want to be caught flat-footed if a variant-specific booster was needed.

They decided by the next Monday it was time to take action. They would develop a new version of the vaccine, one that more closely matched the mutations seen in the strain that circulated in South Africa, and which could potentially be given as a booster shot to better protect people who had gotten the original vaccine.

“It really highlights the fact that we need to continue to stay vigilant,” Moderna’s president, Stephen Hoge, said. “This virus is evolving, it’s changing its stripes. And we need to keep testing the new variants, and make sure the vaccine works against them.”

Moderna repeated the steps it took a year earlier: it quickly designed a new variant vaccine and manufactured an initial batch for human testing, shipping it to NIAID in late February, a year to the day after it had shipped the original batch of the original vaccine. The new batch was called mRNA-1273.351, appending the “351” because researchers initially called the variant seen in South Africa “B.1.351.”

“Moderna is going to keep chasing the variants until the pandemic is under control,” Bancel said that day.

Moderna also developed other plans to test. It would try a third dose of its original vaccine, given several months after the second dose, to see if that booster shot would protect against variants. It would also develop a combined vaccine that targeted both the original strain and the Beta strain.

Once again, volunteers stepped up to test these various approaches. Neal Browning, the Microsoft engineer who was the second person to get Moderna’s vaccine, showed up once again to volunteer. In the intervening year, he had gotten married, in a small outdoor ceremony to minimize Covid risk. Now he received a third dose of the Moderna vaccine. He felt tenderness at the injection site and a low-grade fever and chills, but the symptoms went away after several hours. He continued to visit the research site to give blood samples to be analyzed for immune responses.

By early May, Moderna had some answers. It gave booster shots — either the original vaccine or the Beta variant – targeting vaccine — to people about six to eight months after they had been vaccinated with two doses of the original vaccine. The company found that in the new analysis, both types of booster shots increased neutralizing antibodies against the Beta variant. And they increased antibodies against a related variant that had been detected in Brazil. But the newer version of the vaccine that targeted Beta induced a stronger immune response against the Beta variant than the booster shot of Moderna’s original vaccine.

At the time, Moderna’s plan was to continue testing the different booster approaches, with an eye toward possibly getting government approval to sell the booster shot that specifically targeted the Beta variant. But it didn’t seem particularly urgent. The existing mass vaccination campaign was making good progress at the time.

Then, with the virus on the retreat in the United States, scientists discovered a new variant driving an alarming surge in India. This variant had already jumped to other countries, including the United States. Initially, it was code-named B.1.617.2. It was even more contagious than the Alpha variant and there were fears that it could evade vaccines. This was the Delta variant.

The previous winter the hope provided by vaccines was juxtaposed with the deadliest virus surge in the United States. Again, in early summer 2021, the lifting of mask mandates and reopening of public life was bringing great hope and a sense of relief. And again, this would be juxtaposed with public-health officials sounding the alarm about the Delta variant. It could become the dominant strain of the virus in the United States, they said. The best way to stop its spread, officials said, was to get more people vaccinated, with any of the three vaccines available.

By mid-June, about 55 percent of the US adult population was fully vaccinated, which was good but still left many people exposed to the new Delta variant that spread much more easily than earlier strains. And there were clear geographic vulnerabilities. The Northeast United States had higher vaccination rates than the national average, particularly in some New England states, like Vermont with its 62 percent vaccination rate. But in the South the numbers were much lower in states like Alabama, where only 30 percent were fully vaccinated.

The high proportions of unvaccinated people in those places would serve as a breeding ground for Delta. And the more the variant spread, the more it could mutate into more variants.

By late July, the effects of an ill-fated combination — stubbornly low vaccination rates in some regions, the winding down of masking and distancing, and a rapidly spreading Delta strain—were clearer. Infections, hospitalizations, and deaths were climbing again, especially in open states like Florida, which suffered one of the highest rates of Covid-19 hospitalizations, and low-vaccinated states.

Doctors and nurses who thought they had put the worst of the pandemic behind them were once again scrambling to treat severely ill Covid-19 patients in intensive-care units. By the end of August, the United States was averaging about fifteen hundred Covid-19 deaths a day, versus fewer than two hundred in early July. Nearly all of the patients who ended up in the ICU were unvaccinated.

Some vaccinated people were beginning to test positive for Covid-19, too — commonly called “breakthrough” cases—and a few progressed to severe cases. The vaccines, after all, weren’t 100 percent effective in the clinical trials, either. A small percentage of vaccinated people in the studies got sick with Covid. But it was becoming clear that the vaccines weren’t entirely blocking transmission of the virus or stopping asymptomatic infections, as initially hoped.

Vaccinated people were better protected than unvaccinated people, even when Delta took over. In states like Massachusetts, less than 1 percent of fully vaccinated people in the state had tested positive for Covid-19 by the fall of 2021. Other analysis showed that people who weren’t fully vaccinated were nearly five times more likely to get infected, ten times more likely to be hospitalized and eleven times more likely to die from Covid than fully vaccinated people.

But Delta reminded people, or made them understand for the first time, that the vaccines weren’t bullet-proof. New indoor mask mandates were imposed, including at schools, where educators just weeks earlier had been eager for the first normal back-to-school season in two years. No vaccine was yet authorized for children under twelve (both Moderna and Pfizer were studying that population), raising concerns that Delta would spread rapidly among them as they gathered in classrooms.

By the end of the summer, people wondered if the pandemic would ever end. Some started talking about the coronavirus as endemic, not a pandemic.

And a big slice of America was still saying “No thanks” to the vaccine.

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5 reasons you should buy a cheap phone over an expensive one

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5 reasons you should buy a cheap phone over an expensive one
Moto G22 face down on top of a wall



The Moto G22 on a wall.
(Image credit: Future)

If you’re looking for a new phone, a key consideration is always budget – you want to buy the best phone you can afford. But maybe, even if you’ve got the money for a premium device, you should still opt for a cheap phone.

“Wait,” you’re probably thinking, “are you asking me to spend less than I’m able on my new phone?”  Yes, I am – you’re absolutely right.

You see, despite budget phones being weaker than premium ones in quite a few ways (obviously), there are a few departments in which they actually beat top-end models.

So we’re going to run through some different areas in which cheap phones actually trump their pricier rivals. 

1. It costs less money

Okay, we’ve got to start with the really, really obvious point. A cheap phone is – you guessed it – cheaper than an expensive one.

If you spend less on your phone, you’ve got more to spend on the best power banks, phone cases, charging cables, and so on. Plus, you’ve got extra for non-smartphone things. Y’know: bills, food, transport, and so on.

Smartphones operate on the rule of diminishing returns: a $400 smartphone is not twice as good as a $200 one, and a $1,200 phone isn’t twice as good as a $600 version or four times better in any way than a $300 one.

So if you want the best bang for your buck, a budget mobile will get you there.

Moto G9 Power

The Moto G9 Power has a massive battery. (Image credit: Future)

2. Much better battery life

Phones don’t have great battery life sometimes: when you factor in features like 5G, high refresh rates, top-end processors, and so on, a giant battery can get worn down incredibly quickly.

But you know what cheap phones don’t have? That’s right – any of those features. If a phone is 4G-only, has a low-res screen, and only runs with a middling chipset, it uses the battery at a much slower rate. All of the longest-lasting smartphones are budget ones.

That’s doubly the case when you consider that cheap phone makers like to use huge batteries in their phones – plenty have 5,000mAh power packs. Motorola has even used 6,000mAh ones in some phones, and certain Chinese rugged phone brands have gone even higher.

If you want a long-lasting phone, you’ve got to opt for a cheap handset with fewer features. It also makes such devices reliable for more extended periods.

3. Hardier designs

Glass has become one of the most commonly-used materials for smartphones – it adds to a premium-feeling build and looks good from all angles. 

But you know what glass isn’t? Durable. It can easily smash from an impact like a drop. It’s also slippery, making glass phones harder to hold. Because of this, mid-range and premium phones are more susceptible to damage, even if brands slap silly marketing terms on them like ‘Gorilla Glass Victus’ or ‘Ceramic Shield’.

Cheap phone makers generally stay away from glass. This is mainly because of cost, but it’s beneficial for affordable phone fans because plastic is hardier.

A plastic phone is much more likely to survive a drop or hard knock, letting you avoid the experience of having to get your device repaired as often (or ever, hopefully).

Realme 9 Pro Plus

The Realme 9 Pro Plus has a cool-looking, yet plastic, rear. (Image credit: Future)

4. Cooler chipsets

Cheap phones often have cooler chipsets. No, we don’t mean ‘sunglasses and Tommy Bahama shirt cool’ – we mean temperature-wise.

Premium phones get top-end chipsets, which provide loads of processing power for tasks like games. An annoying side-effect of loads of power, though, is that these chips can get incredibly hot if you use them for long periods.

Counter-intuitively, this means that mid-range chips can be better for gaming if you like playing for extended amounts of time, and don’t need the most top-end graphics available to you.

As you can imagine, budget phones often have weaker internals, so they generally don’t have overheating issues, and are fine for gaming. Plus, in this day and age, you rarely find phones that are slow, even in the lower-cost market.

5. A bigger range of fingerprint scanners

There’s a trend in the premium phone market towards in-screen fingerprint scanners, where the sensor for unlocking your phone is embedded under the display.

This is a fine way of unlocking your device for some, but if you prefer a back- or side-mounted scanner, you’re mostly out of luck at the top end of the market.

That’s not the case for cheap phones, though: you’ll find those digit sensors all over the place in the lower end of the market. Some phones have them in-screen, others have them on one or both sides of the phone, while plenty have the scanner on the back.

So if you like tapping the rear of your phone to unlock it, or caressing the side of the device, instead of just tapping the screen, budget devices are, in fact, the best phones for you.

Tom Bedford

Tom’s role in the TechRadar team is to specialize in phones and tablets, but he also takes on other tech like electric scooters, smartwatches, fitness, mobile gaming and more. He is based in London, UK.

He graduated in American Literature and Creative Writing from the University of East Anglia. Prior to working in TechRadar freelanced in tech, gaming and entertainment, and also spent many years working as a mixologist. Outside of TechRadar he works in film as a screenwriter, director and producer.

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We’re in love with this leaked Xbox Elite Series 2 controller design

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We’re in love with this leaked Xbox Elite Series 2 controller design
An Xbox Elite Controller Series 2 in white



(Image credit: Nicholas Lugo)

The Xbox Elite Series 2 wireless controller looks like it’s getting a brand new color variant with a White Edition.

The Xbox Elite Wireless Controller Series 2 has so far only been available in its default black color scheme. But a short clip shared on Twitter (opens in new tab) by leaker Rebs Gaming shows off a new white edition in the flesh.

The clip starts by showing the premium Xbox Series X|S controller’s box. Next, we’re given a look at the controller itself, which wears a clean white-on-black coat.

All the usual Elite Controller bells and whistles are accounted for. That includes the carry case, swappable analog sticks and customizable back paddle buttons. It looks like the genuine article, though we’ve heard nothing from Microsoft to confirm if or when the pad will actually be released.

A sign of pads to come?

Leak: I think this is our first footage of the Xbox Elite Series 2 White Edition controller. A leaked image of the controller was shown by @IdleSloth84 back in March. Source: https://t.co/WfMCEk3FQv#Xbox #XboxOne #XboxSeriesX pic.twitter.com/t97qbaNPCuAugust 8, 2022

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Okay, sure, the White Edition isn’t exactly the most daring design Microsoft could’ve chosen for its Elite pad. But it’s nonetheless eye-catching. I think that keeping certain parts of the controller black – like the sticks and grips – is a smart aesthetic choice. They contrast really nicely with the white center.

The Elite Series 2 is an excellent controller. But it’s lacking the one thing that the regular Xbox Wireless Controller has in abundance: color options. We’ve seen countless bold designs for the standard Xbox controller, including an eye-popping special edition for Forza Horizon 5 and a stunning hot pink design. But the Elite hasn’t really had the same treatment yet.

I hope that this new White Edition not only comes to market, but that it’s also a gateway for more ambitious designs for Xbox’s top pad. Seriously, a purple Elite pad would be an instant buy for me, and probably for many others, too.

Rhys Wood

Rhys is Hardware Writer for TechRadar Gaming, and while relatively fresh to the role, he’s been writing in a professional capacity for years. A Media, Writing and Production graduate, Rhys has prior experience creating written content for app developers, IT firms, toy sellers and the main TechRadar site. His true passions, though, lie in video games, TV, audio and home entertainment. When Rhys isn’t on the clock, you’ll usually find him logged into Final Fantasy 14, Halo Infinite or Sea of Thieves.

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Street Fighter 6 is bringing the ‘80s (and feet) back

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Street Fighter 6 is bringing the ‘80s (and feet) back

Here come some new challengers. At the end of EVO 2022’s Street Fighter V tournament, Capcom revealed two more characters coming to the roster of Street Fighter 6: Juri, the “I can fix her” returning fighter, and newcomer Kimberly, an ‘80s-obsessed teen.

Kimberly, the spunky new ninja, and Juri, the sadistic thrill-seeker, join #StreetFighter6 when it arrives in 2023! Spray cans, a portable cassette player, and motorcyles have never looked more fresh. ️ pic.twitter.com/Lnw87p27aP

— Street Fighter (@StreetFighter) August 8, 2022

Student of Guy and successor to the bushinryu tradition, Kimberly is spunky and colorful with an affinity for spray painting her enemies midmatch. Though Kimberly is a teenager and Street Fighter 6 seems to be set in the current day, she’s enamored with all things ‘80s, carrying around a cassette player that some younger players probably won’t even recognize.

It’s like Capcom is aware that, in addition to its younger audience, there’s a certain subset of older Street Fighter players rising from their creaking knees and aching back looking at the ‘80s with fondness. In that way, Kimberly is a send-up, a reminder of simpler times. In other ways, she’s a very rude reminder that those happy days are so far behind us now that current teenagers are adopting the aesthetic because it’s quaintly “retro.” Thanks, Capcom, for reminding me I’m old.

Accompanying Kimberly in the character reveal is Juri, a character first introduced in Street Fighter IV. Juri arrives in flashy style with an homage to the Akira slide that’s been having a moment lately, as it was also used to awesome effect in Jordan Peele’s Nope. Juri seems a bit edgier than Kimberly, stomping all over her enemies in bare feet emphasized in ways that would make Bob Odenkirk click “like.” It’s always neat when companies seemingly embrace the thirst players have for its characters.

We’ll get the chance to see more of Juri and Kimberly’s stories when Street Fighter 6 launches on Xbox, PC, and PlayStation in 2023.

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