vox--2020-08-13--Trump campaign attack on Kamala Harris’s citizenship is right out of the birtherism playbook

If you thought Trumpworld moved past birtherism , think again .
Soon after presumptive Democratic nominee Joe Biden introduced Kamala Harris as his presidential running mate on Tuesday , the Trump campaign got busy trying to revive racist conspiracy theories of the sort Donald Trump rode to political prominence back in 2011 .
Trump campaign legal adviser Jenna Ellis retweeted an op-ed written by law professor John Eastman in which he argues Harris is “ not entitled to birthright citizenship under the 14th Amendment as originally understood , ” citing a fringe legal theory holding that children of temporary visitors @ @ @ @ @ @ @ even if they are born here .
Ellis is clearly trying to gin up controversy about whether Harris , a Black woman who is a natural-born citizen to immigrant parents from India and Jamaica , is actually an American citizen , and therefore eligible to serve as vice president .
Asked for comment by ABC ’ s Will Steakin , Ellis did not back down , saying Harris ’ s eligibility is “ an open question.
” In reality , Harris ’ s eligibility is not up for debate .
But Trump himself @ @ @ @ @ @ @ ’ s citizenship during a news conference on Thursday , when he said of her that “ I just heard it today that she doesn ’ t meet the requirements ” to be vice president .
Then , in a quintessentially Trumpian moment , immediately after amplifying the unfounded idea that Harris isn ’ t actually an American citizen , Trump tried to distance himself from it , saying , “ I have no idea if that ’ s right.
” Kamala Harris is a “ natural born citizen ” under the Constitution @ @ @ @ @ @ @ in Oakland , California .
That fact alone makes her a “ natural born citizen , ” and thus eligible to serve as either president or vice president .
Under the 14th Amendment , “ all persons born or naturalized in the United States , and subject to the jurisdiction thereof , are citizens of the United States and of the state wherein they reside.
” Thus , with a narrow exception for individuals not subject to the “ jurisdiction ” of the United States — that is , people who are not @ @ @ @ @ @ @ in this country is automatically a citizen .
The Supreme Court explained the narrow scope of this “ jurisdiction ” exception in United States v. Wong Kim Ark ( 1898 ) , a case holding that a Chinese American man born in San Francisco was a US citizen .
Certain Native Americans , who historically were exempt from US taxation and primarily subject to tribal law , were not considered citizens even if they were born within US borders .
Similarly , the children of foreign diplomats ( who enjoy diplomatic immunity from @ @ @ @ @ @ @ children of alien enemies , born during and within their hostile occupation ” are also not citizens by birth .
But Harris ’ s parents were not foreign diplomats , and they certainly weren ’ t part of an invading army .
That makes her a natural-born citizen .
Nevertheless , in the Newsweek opinion piece promoted by Ellis , Chapman University law professor John Eastman attempts to lay out a case for Kamala Harris birtherism .
Eastman ’ s primary argument is that there is a missing word in the 14th Amendment @ @ @ @ @ @ @ born or naturalized in the United States , and subject to the jurisdiction thereof ” are citizens .
The phrase “ subject to the jurisdiction thereof , ” Eastman claims , means “ subject to the complete jurisdiction , not merely a partial jurisdiction such as that which applies to anyone temporarily sojourning in the United States ( whether lawfully or unlawfully ) .
” Thus , Eastman suggests , Harris is not a citizen if her parents were not “ lawful permanent residents at the time of her birth.
” This argument @ @ @ @ @ @ @ jurisdiction thereof ” actually mean “ subject to the complete jurisdiction ” is not a new one — in fact , it is very old .
In Wong Kim Ark , the two dissenting justices made a similar claim .
“ Born in the United States , and subject to the jurisdiction thereof , ” according to Chief Justice Melville Fuller ’ s dissent in Wong Kim Ark , means born “ under such circumstances as to be completely subject to that jurisdiction.
” Fuller took an even stingier view of citizenship than @ @ @ @ @ @ @ that only the children of US citizens are entitled to birthright citizenship .
But the fact that the Wong Kim Ark dissent and Eastman both read the word “ complete ” into an amendment that does not use that word deeply undercuts Eastman ’ s argument .
It should go without saying that a dissenting opinion is not the law .
There are also good reasons to believe that the Wong Kim Ark majority opinion is correct and that the dissent misread the 14th Amendment .
The Wong Kim Ark majority produced an @ @ @ @ @ @ @ history of birthright citizenship back to the English common law that existed prior to US independence .
“ The fundamental principle of the common law with regard to English nationality was birth within the allegiance , ” Wong Kim Ark explains .
This rule of citizenship was “ not restricted to natural-born subjects and naturalized subjects , or to those who had taken an oath of allegiance ; but were predicable of aliens in amity , so long as they were within the kingdom.
” This English common law rule , Wong Kim @ @ @ @ @ @ @ in all the English Colonies upon this continent down to the time of the Declaration of Independence , and in the United States afterwards , and continued to prevail under the Constitution as originally established.
” Indeed , the principle that “ all children , born within the dominion of the United States , of foreign parents holding no diplomatic office , became citizens at the time of their birth , does not appear to have been contested or doubted until more than fifty years after the adoption of the Constitution.
” There @ @ @ @ @ @ @ from the rule of birthright citizenship .
In Dred Scott v. Sandford ( 1857 ) , an infamous pro-slavery decision , the Court held that Black people are “ regarded as beings of an inferior order , and altogether unfit to associate with the white race , either in social or political relations ” — and thus not entitled to the rights of citizenship .
But one of the primary purposes of the 14th Amendment was to overturn Dred Scott .
As the Wong Kim Ark majority explained , the amendment sought to @ @ @ @ @ @ @ , which had been denied in the opinion delivered by Chief Justice Taney in Dred Scott.
” This history , in other words , suggests that birthright citizenship was the American rule long before the 14th Amendment was ratified .
This general rule inevitably came into conflict with chattel slavery — which could only exist in a nation that denied enslaved people the full rights of citizenship — but the nation chose birthright citizenship over slavery as part of the settlement that ended the Civil War .
And that settlement was written into @ @ @ @ @ @ @ was ratified .
There is simply no basis , in other words , to deny that the child of immigrants — someone like Kamala Harris — is a natural-born citizen .
It ’ s not a shock that the Trump campaign would so quickly resort to pushing conspiracy theories of this sort about the first Black and Indian American woman to appear on a major party ’ s presidential ticket .
Trump has a long and sordid history of doing the same about America ’ s first Black president .
During the runup @ @ @ @ @ @ @ campaign in 2012 , Trump endeared himself to the far right by pushing conspiracy theories about Obama ’ s place of birth .
For instance , during an April 2011 appearance on CNN , Trump said , “ he could have been born in Kenya and gone over to the United States .
Everybody wants to be a US citizen , and his grandparents put an ad in saying he was born in the United States because of all the benefits you get from being born in the United States.
” Obama responded @ @ @ @ @ @ @ his long-form birth certificate .
But even then , Trump wouldn ’ t admit he was wrong , and in the months that followed , he repeatedly claimed Obama ’ s birth certificate was fake .
When then-Republican presidential nominee Trump finally addressed his history of birtherism during a September 2016 press conference , he went as far as to suggest he deserved praise for raising the issue , saying unapologetically , “ I finished it .
President Obama was born in the United States — period.
’ ’ But there are indications @ @ @ @ @ @ @ persisted into the White House .
In November 2017 , the New York Times reported that Trump “ used closed-door conversations to question the authenticity of President Barack Obama ’ s birth certificate.
” Reached for comment on Thursday afternoon , Biden campaign spokesperson Andrew Bates said Trump “ was the national leader of the grotesque , racist birther movement with respect to President Obama and has sought to fuel racism and tear our nation apart on every single day of his presidency .
“ So it ’ s unsurprising , but no @ @ @ @ @ @ @ a fool of himself straining to distract the American people from the horrific toll of his failed coronavirus response that his campaign and their allies would resort to wretched , demonstrably false lies in their pathetic desperation , ” Bates added .
The Trump campaign didn ’ t immediately respond to an inquiry about whether Ellis ’ s comments reflect the official position of the campaign .
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Today , we ’ re humbled to say that nearly 20,000 people have chipped in .
The reason is both lovely and surprising : Readers told us that they contribute both because they value explanation and because they value that other people can access it , too .
We have always believed that explanatory journalism is vital for a functioning democracy .
That ’ s never been more important than today , during a public health crisis , racial justice protests , a recession , and a presidential election .
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If you thought Trumpworld had moved past birtherism, think again.
Hours after presumptive Democratic nominee Joe Biden formally introduced Kamala Harris as his presidential running mate on Wednesday, the Trump campaign got busy trying to revive racist conspiracy theories of the sort Donald Trump rode to political prominence back in 2011.
Trump campaign legal adviser Jenna Ellis retweeted an op-ed written by law professor John Eastman in which he argues Harris is “not entitled to birthright citizenship under the 14th Amendment as originally understood,” citing a fringe legal theory holding that children of temporary visitors to the country are not conferred citizenship even if they are born here.
Ellis is clearly trying to gin up controversy about whether Harris, a Black woman who is a natural-born citizen to immigrant parents from India and Jamaica, is actually an American citizen, and therefore eligible to serve as vice president.
Trump campaign legal advisor Jenna Ellis RTs a link to that birther op-ed about @KamalaHarris, putting the campaign's handprint on something that Democrats are very happy to rebut/talk about. pic.twitter.com/qopyGpZCfY — Dave Weigel (@daveweigel) August 13, 2020
Asked for comment by ABC’s Will Steakin, Ellis did not back down, saying Harris’s eligibility is “an open question.”
In reality, Harris’s eligibility is not up for debate. But Trump himself gave voice to this attack on Harris’s citizenship during a news conference on Thursday, when he said of her that “I just heard it today that she doesn’t meet the requirements” to be vice president.
Then, in a quintessentially Trumpian moment, immediately after amplifying the unfounded idea that Harris isn’t actually an American citizen, Trump tried to distance himself from it, saying, “I have no idea if that’s right.”
Holy shit. Trump pushes a baseless, birther-style theory about Kamala Harris that holds she's not a citizen because birthright citizenship isn't a thing.
"I just heard it today that she doesn't meet the requirements ... I have no idea if that's right." pic.twitter.com/ZIXYrleuVf — Aaron Rupar (@atrupar) August 13, 2020
Kamala Harris is a “natural born citizen” under the Constitution
Sen. Harris was born to immigrant parents in Oakland, California. That fact alone makes her a “natural born citizen,” and thus eligible to serve as either president or vice president.
Under the 14th Amendment, “all persons born or naturalized in the United States, and subject to the jurisdiction thereof, are citizens of the United States and of the state wherein they reside.” Thus, with a narrow exception for individuals not subject to the “jurisdiction” of the United States — that is, people who are not subject to US law — anyone born in this country is automatically a citizen.
The Supreme Court explained the narrow scope of this “jurisdiction” exception in United States v. Wong Kim Ark (1898), a case holding that a Chinese American man born in San Francisco was a US citizen. Certain Native Americans, who historically were exempt from US taxation and primarily subject to tribal law, were not considered citizens even if they were born within US borders. Similarly, the children of foreign diplomats (who enjoy diplomatic immunity from US law), and “the children of alien enemies, born during and within their hostile occupation” are also not citizens by birth.
But Harris’s parents were not foreign diplomats, and they certainly weren’t part of an invading army. That makes her a natural-born citizen.
Nevertheless, in the Newsweek opinion piece promoted by Ellis, Chapman University law professor John Eastman attempts to lay out a case for Kamala Harris birtherism. Eastman’s primary argument is that there is a missing word in the 14th Amendment’s declaration that “all persons born or naturalized in the United States, and subject to the jurisdiction thereof,” are citizens.
The phrase “subject to the jurisdiction thereof,” Eastman claims, means “subject to the complete jurisdiction, not merely a partial jurisdiction such as that which applies to anyone temporarily sojourning in the United States (whether lawfully or unlawfully).” Thus, Eastman suggests, Harris is not a citizen if her parents were not “lawful permanent residents at the time of her birth.”
This argument that the words “subject to the jurisdiction thereof” actually mean “subject to the complete jurisdiction” is not a new one — in fact, it is very old. In Wong Kim Ark, the two dissenting justices made a similar claim. “Born in the United States, and subject to the jurisdiction thereof,” according to Chief Justice Melville Fuller’s dissent in Wong Kim Ark, means born “under such circumstances as to be completely subject to that jurisdiction.”
Fuller took an even stingier view of citizenship than Eastman — Fuller’s dissent suggests that only the children of US citizens are entitled to birthright citizenship. But the fact that the Wong Kim Ark dissent and Eastman both read the word “complete” into an amendment that does not use that word deeply undercuts Eastman’s argument. It should go without saying that a dissenting opinion is not the law.
There are also good reasons to believe that the Wong Kim Ark majority opinion is correct and that the dissent misread the 14th Amendment.
The Wong Kim Ark majority produced an unusually scholarly opinion, which traced the history of birthright citizenship back to the English common law that existed prior to US independence. “The fundamental principle of the common law with regard to English nationality was birth within the allegiance,” Wong Kim Ark explains. This rule of citizenship was “not restricted to natural-born subjects and naturalized subjects, or to those who had taken an oath of allegiance; but were predicable of aliens in amity, so long as they were within the kingdom.”
This English common law rule, Wong Kim Ark continues, “was in force in all the English Colonies upon this continent down to the time of the Declaration of Independence, and in the United States afterwards, and continued to prevail under the Constitution as originally established.” Indeed, the principle that “all children, born within the dominion of the United States, of foreign parents holding no diplomatic office, became citizens at the time of their birth, does not appear to have been contested or doubted until more than fifty years after the adoption of the Constitution.”
There was one very significant early American departure from the rule of birthright citizenship. In Dred Scott v. Sandford (1857), an infamous pro-slavery decision, the Court held that Black people are “regarded as beings of an inferior order, and altogether unfit to associate with the white race, either in social or political relations” — and thus not entitled to the rights of citizenship.
But one of the primary purposes of the 14th Amendment was to overturn Dred Scott. As the Wong Kim Ark majority explained, the amendment sought to “establish the citizenship of free negroes, which had been denied in the opinion delivered by Chief Justice Taney in Dred Scott.”
This history, in other words, suggests that birthright citizenship was the American rule long before the 14th Amendment was ratified. This general rule inevitably came into conflict with chattel slavery — which could only exist in a nation that denied enslaved people the full rights of citizenship — but the nation chose birthright citizenship over slavery as part of the settlement that ended the Civil War.
And that settlement was written into the Constitution itself when the 14th Amendment was ratified.
There is simply no basis, in other words, to deny that the child of immigrants — someone like Kamala Harris — is a natural-born citizen.
Once a birther, always a birther
It’s not a shock that the Trump campaign would so quickly resort to pushing conspiracy theories of this sort about the first Black and Indian American woman to appear on a major party’s presidential ticket. Trump has a long and sordid history of doing the same about America’s first Black president.
During the runup to President Barack Obama’s reelection campaign in 2012, Trump endeared himself to the far right by pushing conspiracy theories about Obama’s place of birth. For instance, during an April 2011 appearance on CNN, Trump said, “he could have been born in Kenya and gone over to the United States. Everybody wants to be a US citizen, and his grandparents put an ad in saying he was born in the United States because of all the benefits you get from being born in the United States.”
Obama responded that same month by releasing copies of his long-form birth certificate. But even then, Trump wouldn’t admit he was wrong, and in the months that followed, he repeatedly claimed Obama’s birth certificate was fake.
An 'extremely credible source' has called my office and told me that @BarackObama's birth certificate is a fraud. — Donald J. Trump (@realDonaldTrump) August 6, 2012
When then-Republican presidential nominee Trump finally addressed his history of birtherism during a September 2016 press conference, he went as far as to suggest he deserved praise for raising the issue, saying unapologetically, “I finished it. President Obama was born in the United States — period.”
But there are indications that Trump’s interest in birtherism persisted into the White House. In November 2017, the New York Times reported that Trump “used closed-door conversations to question the authenticity of President Barack Obama’s birth certificate”:
One senator who listened as the president revived his doubts about Mr. Obama’s birth certificate chuckled on Tuesday as he recalled the conversation. The president, he said, has had a hard time letting go of his claim that Mr. Obama was not born in the United States. The senator asked not to be named to discuss private conversations.
Reached for comment on Thursday afternoon, Biden campaign spokesperson Andrew Bates said Trump “was the national leader of the grotesque, racist birther movement with respect to President Obama and has sought to fuel racism and tear our nation apart on every single day of his presidency.
“So it’s unsurprising, but no less abhorrent, that as Trump makes a fool of himself straining to distract the American people from the horrific toll of his failed coronavirus response that his campaign and their allies would resort to wretched, demonstrably false lies in their pathetic desperation,” Bates added.
The Trump campaign didn’t immediately respond to an inquiry about whether Ellis’s comments reflect the official position of the campaign.
Will you become our 20,000th supporter? When the economy took a downturn in the spring and we started asking readers for financial contributions, we weren’t sure how it would go. Today, we’re humbled to say that nearly 20,000 people have chipped in. The reason is both lovely and surprising: Readers told us that they contribute both because they value explanation and because they value that other people can access it, too. We have always believed that explanatory journalism is vital for a functioning democracy. That’s never been more important than today, during a public health crisis, racial justice protests, a recession, and a presidential election. But our distinctive explanatory journalism is expensive, and advertising alone won’t let us keep creating it at the quality and volume this moment requires. Your financial contribution will not constitute a donation, but it will help keep Vox free for all. Contribute today from as little as $3.


vox--2020-08-13--The company behind Fortnite dared Apple to shutter its game on iPhones. Now Apple has gone ahead and

The company behind Fortnite dared Apple to shutter its game on iPhones. Now Apple has gone ahead and sort of done that.

The company that owns Fortnite is making an in-your-face challenge to Apple : We ’ re not going to obey the rules you ’ ve set for your powerful App Store .
And we dare you to do something about it .
Now Apple has done something : After Epic Games announced this morning that it was encouraging Fortnite players to bypass Apple ’ s in-house payment system — an intentional violation of Apple ’ s app policies — Apple has removed Fortnite from its App Store , claiming that Epic wanted “ a special arrangement ” that other developers @ @ @ @ @ @ @ means : If you ’ ve already downloaded Fornite to your iPhone or iPad , you can still use it .
But the move does mean that Epic won ’ t be able to update the app — something that it did regularly to fix bugs and introduce new features .
So if the situation doesn ’ t change , Epic will eventually have to abandon Fortnite ’ s Apple users .
And now Epic , in response to Apple ’ s response , says it is filing an antitrust lawsuit against Apple @ @ @ @ @ @ @ also telling its Apple users they won ’ t be able to play future versions of its game : “ Because Apple has BLOCKED your ability to update , when Fortnite Chapter 2 - Season 4 releases you will NOT be able to play the new Season on iOS.
” It ’ s a fascinating standoff between a very profitable , highly valued gaming company and one of the most powerful companies in the world .
The way it plays out could have consequences for Apple , its tech rivals — and antitrust @ @ @ @ @ @ @ developer behind Fortnite and other games , announced on Thursday morning that players who want to buy Fortnite ’ s virtual currency would no longer have to buy it via Apple ’ s App Store .
Instead , it told them they could buy it directly from Epic .
The difference for players , however , is that Epic would charge them 20 percent less if they buy the currency from Epic instead of Apple .
It ’ s a small change that ’ s a big deal because Apple has explicitly prohibited @ @ @ @ @ @ @ runs around its powerful App Store .
Instead , Apple wants developers to sell their digital goods within its marketplace , where it takes a cut of up to 30 percent for each purchase .
That stance has long upset developers , who argue that Apple ’ s fee is too onerous and gives its home-grown products a leg up on competitors by essentially letting Apple sell its own stuff with a much better profit margin .
Apple sells its music service , for instance , for $ 10 a month ; if @ @ @ @ @ @ @ Apple ’ s store for the same price , it would have to fork over as much as $ 3 of that to Apple .
So , over time , some big players , including Netflix and Spotify , have stopped selling subscriptions to their services from the Apple App Store altogether .
You can use Spotify and Netflix on Apple devices , but if you want to pay for them , you have to visit those companies ’ websites .
Spotify has also filed a complaint with European antitrust regulators , who @ @ @ @ @ @ @ .
Apple has also drawn attention from US lawmakers like Sen. Elizabeth Warren , who has said the company is trying to “ lock out ” competitors .
Last month , Apple ’ s policies came under fire when CEO Tim Cook testified at a congressional antitrust hearing .
And in the past few weeks , Apple ’ s App Store policies have also generated conflict with both Facebook and Microsoft , which complained that Apple was barring gaming services they wanted to distribute through the App Store .
But no developer has @ @ @ @ @ @ @ broadcasting that it wasn ’ t going to play by Apple ’ s rules .
For the time being , if you try to buy 1,000 “ V Bucks ” in Fornite , Epic will ask you whether you want to spend $ 10 to do so via Apple ’ s store or $ 8 to do it from Epic : Epic explained the move to its users by describing it as new “ discount pricing.
” But in a post aimed at the media , the company went out of its way @ @ @ @ @ @ @ Apple ’ s 30 percent tax , as well as a similar one that Google ’ s app store also charges .
“ Apple and Google collect an exorbitant 30 % fee on all payments ” for virtual goods , the post said , pointing out that Apple doesn ’ t collect a similar fee for real-world goods developers like Amazon , McDonald ’ s , and Uber sell via Apple apps .
“ Epic direct payment simply offers players the same kinds of payment options as these other apps.
” While Epic @ @ @ @ @ @ @ s and Google ’ s app stores , Apple is the company that clearly rankles Epic CEO Tim Sweeney , who has been complaining about the company on Twitter for weeks : So now Sweeney is making a very big gamble .
He ’ s daring Apple to either back down from its stance or shutter Fornite ’ s Apple app and see what millions of Fortnite players do next .
In the worst case , the company seems to be thinking , it can survive with a player base that comes from @ @ @ @ @ @ @ PCs .
For now , Apple is taking Epic head on — which is likely the only move it could make , in the short term : If it allowed Epic to run an alternate payments system while preventing other developers from doing so , it would have an even bigger headache .
But longer term , this may increase pressure on Apple to change its policies .
Here ’ s a statement from Apple PR , released after the company removed Fortnite from the App Store : “ Today , Epic Games @ @ @ @ @ @ @ App Store guidelines that are applied equally to every developer and designed to keep the store safe for our users .
As a result their Fortnite app has been removed from the store .
Epic enabled a feature in its app which was not reviewed or approved by Apple , and they did so with the express intent of violating the App Store guidelines regarding in-app payments that apply to every developer who sells digital goods or services .
“ Epic has had apps on the App Store for a decade , and @ @ @ @ @ @ @ - including its tools , testing , and distribution that Apple provides to all developers .
Epic agreed to the App Store terms and guidelines freely and we ’ re glad they ’ ve built such a successful business on the App Store .
The fact that their business interests now lead them to push for a special arrangement does not change the fact that these guidelines create a level playing field for all developers and make the store safe for all users .
We will make every effort to work with Epic @ @ @ @ @ @ @ return Fortnite to the App Store.
” While Epic doesn ’ t have the same kind of awareness of big tech players like Facebook and Amazon , the company certainly has the capacity to fight Apple .
Epic says it generated earnings of $ 730 million last year on revenue of $ 4.7 billion ; much of that money came from Fornite , which Epic says has 350 million players worldwide .
But while Epic has substantial resources , losing access to Apple customers could still cost it real money .
SensorTower estimates @ @ @ @ @ @ @ on Fortnite since March 2018 .
That would mean after Apple took 30 percent of that haul , Epic would be left with $ 840 million .
Those numbers have presumably been trending down as Fortnite ’ s red-hot popularity cooled , but Epic would certainly like to have those customers again .
I ’ ve asked Epic for comment and will update if it provides any .
In the meantime , it may be worth noting that Epic co-founder Mark Rein retweeted my analysis of this morning ’ s move , without @ @ @ @ @ @ @ s move is interesting .
It comes after Epic raised a staggering $ 1.8 billion , which values Sweeney ’ s company at more than $ 17 billion .
But it also comes after Cook ’ s appearance in front of Congress .
Had Epic done this in the runup to that event , the situation certainly would have been raised by lawmakers .
The move also happens on the same day that Apple ’ s plans to sell even more of its own digital services have come into focus .
Bloomberg reports @ @ @ @ @ @ @ Apple subscriptions to products like its music , video , and gaming services — later this fall , at a discount .
Will you become our 20,000th supporter ?
When the economy took a downturn in the spring and we started asking readers for financial contributions , we weren ’ t sure how it would go .
Today , we ’ re humbled to say that nearly 20,000 people have chipped in .
The reason is both lovely and surprising : Readers told us that they contribute both because they value explanation and @ @ @ @ @ @ @ access it , too .
We have always believed that explanatory journalism is vital for a functioning democracy .
That ’ s never been more important than today , during a public health crisis , racial justice protests , a recession , and a presidential election .
But our distinctive explanatory journalism is expensive , and advertising alone won ’ t let us keep creating it at the quality and volume this moment requires .
Your financial contribution will not constitute a donation , but it will help keep Vox free for all @ @ @ @ @ @ @ $ 3 .

The company that owns Fortnite is making an in-your-face challenge to Apple: We’re not going to obey the rules you’ve set for your powerful App Store. And we dare you to do something about it.
Now Apple has done something: After Epic Games announced on April 13 that it was encouraging Fortnite players to bypass Apple’s in-house payment system — an intentional violation of Apple’s app policies — Apple removed Fortnite from its App Store, claiming that Epic wanted “a special arrangement” that other developers don’t get.
What that means: If you’ve already downloaded Fortnite to your iPhone or iPad, you can still use it. But the move does mean that Epic won’t be able to update the app — something that it did regularly to fix bugs and introduce new features. So if the situation doesn’t change, Epic will eventually have to abandon Fortnite’s Apple users.
And now Epic, in response to Apple’s response, says it is filing an antitrust lawsuit against Apple in US District Court. It is also telling its Apple users they won’t be able to play future versions of its game: “Because Apple has BLOCKED your ability to update, when Fortnite Chapter 2 - Season 4 releases you will NOT be able to play the new Season on iOS.”
It’s a fascinating standoff between a very profitable, highly valued gaming company and one of the most powerful companies in the world. The way it plays out could have consequences for Apple, its tech rivals — and antitrust regulators.
Epic, the North Carolina-based developer behind Fortnite and other games, announced on the morning of April 13 that players who want to buy Fortnite’s virtual currency would no longer have to buy it via Apple’s App Store. Instead, it told them they could buy it directly from Epic. The difference for players, however, is that Epic would charge them 20 percent less if they buy the currency from Epic instead of Apple.
It’s a small change that’s a big deal because Apple has explicitly prohibited developers from promoting these kinds of end runs around its powerful App Store. Instead, Apple wants developers to sell their digital goods within its marketplace, where it takes a cut of up to 30 percent for each purchase.
That stance has long upset developers, who argue that Apple’s fee is too onerous and gives its home-grown products a leg up on competitors by essentially letting Apple sell its own stuff with a much better profit margin. Apple sells its music service, for instance, for $10 a month; if a rival music service sold subscriptions via Apple’s store for the same price, it would have to fork over as much as $3 of that to Apple.
So, over time, some big players, including Netflix and Spotify, have stopped selling subscriptions to their services from the Apple App Store altogether. You can use Spotify and Netflix on Apple devices, but if you want to pay for them, you have to visit those companies’ websites. Spotify has also filed a complaint with European antitrust regulators, who are now investigating Apple’s policies.
Apple has also drawn attention from US lawmakers like Sen. Elizabeth Warren, who has said the company is trying to “lock out” competitors. Last month, Apple’s policies came under fire when CEO Tim Cook testified at a congressional antitrust hearing.
And in the past few weeks, Apple’s App Store policies have also generated conflict with both Facebook and Microsoft, which complained that Apple was barring gaming services they wanted to distribute through the App Store.
But no developer has done what Epic did, broadcasting that it wasn’t going to play by Apple’s rules. For the time being, if you try to buy 1,000 “V Bucks” in Fortnite, Epic will ask you whether you want to spend $10 to do so via Apple’s store or $8 to do it from Epic:
Epic explained the move to its users by describing it as new “discount pricing.” But in a post aimed at the media, the company went out of its way to say that it was defying Apple’s 30 percent tax, as well as a similar one that Google’s app store also charges.
“Apple and Google collect an exorbitant 30% fee on all payments” for virtual goods, the post said, pointing out that Apple doesn’t collect a similar fee for real-world goods developers like Amazon, McDonald’s, and Uber sell via Apple apps. “Epic direct payment simply offers players the same kinds of payment options as these other apps.”
Epic’s move affects both Apple’s and Google’s app stores. And later on the same day, Google also kicked Fortnite out of its own app store, prompting another lawsuit from Epic, which repeated most of the arguments it made against Apple earlier in the day.
But Apple is the company that clearly rankles Epic CEO Tim Sweeney, who has been complaining about the company on Twitter for weeks:
Apple's intentional anti-competitive strategy has been running for much longer than most realize. Here they are in 2011 muscling Kindle purchases off of iPhone by demanding 30% of e-book revenue, "which we acknowledge is prohibitive for many things".https://t.co/trnugoOZgV — Tim Sweeney (@TimSweeneyEpic) August 1, 2020
It pains me to complain about Apple in this way. Apple is one of the greatest companies that has ever existed, perhaps the greatest. But they're fundamentally wrong in blocking competition and choice on devices they make, and that holds up entire fields of technological progress. — Tim Sweeney (@TimSweeneyEpic) July 29, 2020
Apple has gone crazy. If colleges hold virtual classes through an iPhone app, Apple could demand 30% of the tuition. Truly, Apple has no right to take any percent of any company’s revenue just because they made the phone people use to access the stuff.https://t.co/Pt2JlS4bvo — Tim Sweeney (@TimSweeneyEpic) July 28, 2020
So now Sweeney is making a very big gamble. He’s daring Apple to either back down from its stance or shutter Fortnite’s Apple app and see what millions of Fortnite players do next. In the worst case, the company seems to be thinking, it can survive with a player base that comes from other platforms, like gaming consoles and PCs.
For now, Apple is taking Epic head on — which is likely the only move it could make, in the short term: If it allowed Epic to run an alternate payments system while preventing other developers from doing so, it would have an even bigger headache. But longer term, this may increase pressure on Apple to change its policies.
Here’s a statement from Apple PR, released after the company removed Fortnite from the App Store:
“Today, Epic Games took the unfortunate step of violating the App Store guidelines that are applied equally to every developer and designed to keep the store safe for our users. As a result their Fortnite app has been removed from the store. Epic enabled a feature in its app which was not reviewed or approved by Apple, and they did so with the express intent of violating the App Store guidelines regarding in-app payments that apply to every developer who sells digital goods or services. “Epic has had apps on the App Store for a decade, and have benefited from the App Store ecosystem - including its tools, testing, and distribution that Apple provides to all developers. Epic agreed to the App Store terms and guidelines freely and we’re glad they’ve built such a successful business on the App Store. The fact that their business interests now lead them to push for a special arrangement does not change the fact that these guidelines create a level playing field for all developers and make the store safe for all users. We will make every effort to work with Epic to resolve these violations so they can return Fortnite to the App Store.”
While Epic doesn’t have the same kind of awareness of big tech players like Facebook and Amazon, the company certainly has the capacity to fight Apple. Epic says it generated earnings of $730 million last year on revenue of $4.7 billion; much of that money came from Fortnite, which Epic says has 350 million players worldwide.
But while Epic has substantial resources, losing access to Apple customers could still cost it real money. SensorTower estimates that Apple customers spent $1.2 billion on Fortnite since March 2018. That would mean after Apple took 30 percent of that haul, Epic would be left with $840 million. Those numbers have presumably been trending down as Fortnite’s red-hot popularity cooled, but Epic would certainly like to have those customers again.
I’ve asked Epic for comment and will update if it provides any. In the meantime, it may be worth noting that Epic co-founder Mark Rein retweeted my analysis of this morning’s move, without comment:
The timing for Sweeney’s move is interesting. It comes after Epic raised a staggering $1.8 billion, which values Sweeney’s company at more than $17 billion. But it also comes after Cook’s appearance in front of Congress. Had Epic done this in the runup to that event, the situation certainly would have been raised by lawmakers.
The move also happens on the same day that Apple’s plans to sell even more of its own digital services have come into focus. Bloomberg reports that Apple plans to sell bundles of Apple subscriptions to products like its music, video, and gaming services — later this fall, at a discount.
Will you become our 20,000th supporter? When the economy took a downturn in the spring and we started asking readers for financial contributions, we weren’t sure how it would go. Today, we’re humbled to say that nearly 20,000 people have chipped in. The reason is both lovely and surprising: Readers told us that they contribute both because they value explanation and because they value that other people can access it, too. We have always believed that explanatory journalism is vital for a functioning democracy. That’s never been more important than today, during a public health crisis, racial justice protests, a recession, and a presidential election. But our distinctive explanatory journalism is expensive, and advertising alone won’t let us keep creating it at the quality and volume this moment requires. Your financial contribution will not constitute a donation, but it will help keep Vox free for all. Contribute today from as little as $3.


vox--2020-08-13--These Covid-19 vaccine candidates could change the way we make vaccines — if they work

As urgency mounts for a Covid-19 coronavirus vaccine , a key question for scientists is whether this pandemic will be the watershed moment for two new technologies that have never before seen widespread use in humans .
If proven effective , these approaches could dramatically speed up the development of other new vaccines and drastically lower costs , heralding a new era in the fight against infectious disease .
The main technologies gaining traction are vaccines that use an adenovirus vector and mRNA .
Rather than construct a new vaccine from scratch , the idea behind these technologies is to @ @ @ @ @ @ @ like a repurposed virus or a nanoparticle , to carry genetic material into a cell .
That material — DNA or RNA — can then code for specific proteins from a virus .
Once one of these delivery platforms are proven safe , it ’ s just a matter of tweaking DNA and RNA strands .
That ’ s much faster than conventional vaccines , which involve culturing large quantities of viruses that are then weakened , inactivated , or separated into tiny fragments and purified — processes that require years of cumbersome @ @ @ @ @ @ @ the new platforms work in a way , that may actually change how other vaccines are produced , ” Rahul Gupta , senior vice president and chief medical and health officer at the March of Dimes , told reporters during a National Press Foundation webinar on August 7 .
“ So we may be at the cusp of very much a new technology that we ’ re going to see for the first time in over a century , basically.
” Researchers using these new platforms have recently posted some encouraging results .
@ @ @ @ @ @ @ published results of its phase 1 and phase 2 clinical trials for its mRNA-based vaccine platform in the journal Nature .
Moderna is now entering phase 3 trials for its mRNA platform for Covid-19 .
Meanwhile , Oxford University ’ s Jenner Institute is partnering with AstraZeneca to develop a vaccine using an adenovirus vector platform .
It has also published some early promising results .
But there is a lot of competition , with more than 200 coronavirus vaccine candidates under investigation around the world .
Two dozen are undergoing testing in @ @ @ @ @ @ @ 3 clinical trials as of August 13 .
A vaccine effort of this scale is astonishing for a disease that was discovered less than a year ago .
But the immense health and economic devastation of the Covid-19 pandemic has prompted an unprecedented level of collaboration among scientists , as well as funding from governments , private companies , and philanthropists .
That ’ s why some scientists expect there will be enough data proving the safety and efficacy of a Covid-19 vaccine in record time , possibly by the end of the @ @ @ @ @ @ @ , widely available vaccine would be a major step toward ending the pandemic .
However , there is no guarantee that any of these candidates will succeed , let alone whether a new vaccine technology will triumph over tried-and-true methods .
Although companies working with the new platforms have readily cleared the earlier stages of clinical trials , they are now at the mercy of larger , slower phase 3 trials , where a lot can happen to derail their progress .
That ’ s why it ’ s important to understand how @ @ @ @ @ @ @ , what they bring to the table , and the critical caveats to consider .
Vaccines work by coaching the immune system to fight off a specific pathogen .
When you get one , your white blood cells are being introduced to a potential threat , such as a virus or bacterium .
That gives the immune system time to start mounting a response so that if the pathogen shows up another time , the body can quickly neutralize it .
Vaccines have been around in various forms for centuries , but the @ @ @ @ @ @ @ ones for diseases such as polio , anthrax , pneumonia , meningitis , Hepatitis A , and influenza .
The conventional strategies for constructing vaccines that offer strong , long-lasting immunity involve mimicking the target .
One of the most effective ways to do this is with a live attenuated vaccine .
Here , a live form of the virus or bacterium is cultivated in such a way that it is weakened when given to a human .
The pathogen can reproduce somewhat , but rarely enough to make the recipient sick .
@ @ @ @ @ @ @ , measles , mumps , and rubella — use live attenuated viruses .
Vaccines can also target toxic products of a bacterium or virus .
Toxoid vaccines , like those for diphtheria and tetanus , are stable and safe but often require multiple doses .
Another approach is to use an inactivated version of the pathogen , usually a live pathogen that has been deliberately killed by heat or with a chemical treatment .
This is the approach behind vaccines for diseases like Hepatitis A and rabies .
Inactivated pathogen vaccines also often @ @ @ @ @ @ @ to retain immunity .
But instead of using whole-virus or bacterium particles , scientists can also use purified fragments of a pathogen — known as antigens — to trigger an immune reaction .
These subunit vaccines tend to be stable , but they ’ re tricky to do right and often generate a weaker immune response than whole-pathogen vaccines .
Developing a vaccine using any of these methods , however , is time-consuming , often taking more than a decade to demonstrate that they ’ re safe and effective .
That ’ s @ @ @ @ @ @ @ the one sweeping the world right now .
The new Covid-19 vaccine platforms harness human cells to make key components Both mRNA vaccines and adenovirus vector vaccines build on the idea of a subunit vaccine .
In the case of SARS-CoV-2 , the virus that causes Covid-19 , the most common subunit of interest is the spike protein .
This protein is the business end of the virus .
It ’ s what the coronavirus uses to dock with the ACE2 receptor on a human cell in order to enter the cell , @ @ @ @ @ @ @ spread to other cells .
Scientists reason that they can coax the immune system to generate antibodies to this spike protein .
Antibodies are proteins made by the immune system that attach to specific parts of a pathogen , thereby disabling it or marking it for destruction by other immune cells .
If antibodies bind to the spike protein of a live SARS-CoV-2 virus , they could prevent it from causing an infection .
But with these new platforms , it ’ s not the spike protein of the virus that ’ s @ @ @ @ @ @ @ genetic instructions for making it .
The main differences between mRNA vaccines and adenovirus vector vaccines are the genetic material they use and how they get it into the cell .
The mRNA vaccines use mRNA , while adenovirus vaccines use DNA .
Once the instructions are inside the cell , the cell ’ s machinery reads them to manufacture the spike protein of the virus .
The newly minted spike proteins are either secreted from the cell or attached to its surface , where other cells from the immune system can identify @ @ @ @ @ @ @ to it .
The process ends up not only mimicking a key structure of the virus but also imitating how the virus works during an infection , which could potentially generate a stronger immune response and yield better protection compared with other approaches .
And because these proteins are produced from within cells rather than injected from the outside , they may be less likely to provoke adverse reactions in the recipient .
On August 11 , President Donald Trump announced that the US government would buy 100 million doses of Moderna ’ @ @ @ @ @ @ @ valued at $ 1.53 billion , bringing the country ’ s total investment in the company to $ 2.48 billion .
( The Department of Health and Human Services previously said it would buy 100 million doses of Pfizer ’ s mRNA vaccine . )
These are just a couple of the big bets the federal government has placed on different vaccine manufacturers , but the fact that it ’ s investing so much in a new approach like mRNA signals how much promise it holds .
mRNA stands for messenger ribonucleic acid @ @ @ @ @ @ @ ’ s copied from DNA in a cell ’ s nucleus and used as the code for making a specific protein .
If you think of the DNA in the nucleus as a giant cookbook containing all the recipes for all the meals you ’ ll ever eat , mRNA is the notecard you use to jot down instructions for making your favorite banana bread .
Compared to DNA , mRNA is shorter in length , less stable , and designed to be disposable .
Your cells are making and breaking down mRNA @ @ @ @ @ @ @ mRNA vaccine , the idea is to get a segment of mRNA that codes for a specific viral protein into a cell .
For vaccine developers , that means that instead of going through the tedious process of isolating and purifying subunits of a virus , they can just change the code in a strand of mRNA .
That makes the development process much faster than conventional approaches , which can take months or years .
“ mRNA can literally be completed in days to weeks to create a brand-new vaccine , ” @ @ @ @ @ @ @ medicine at the University of Pennsylvania .
He noted that it took only 66 days from when the genome of the SARS-CoV-2 virus was sequenced to when the first patient was injected with an mRNA-based Covid-19 vaccine .
One of the challenges with using mRNA is that your body can perceive it as a threat , as many viruses use RNA to encode their genomes .
There are a lot of enzymes in the body that can readily digest RNA before it gets into a cell .
( There are even RNA-digesting enzymes @ @ @ @ @ @ @ strands in the body can trigger inflammation , so to shield the mRNA until it gets into a cell , developers encase it inside a lipid nanoparticle — a tiny oil bubble .
The RNA strand itself is also modified to make it less inflammatory .
Once the mRNA is coded , modified , and encapsulated , it can then be injected .
“ All modified RNA vaccines for Covid are given intramuscularly , just like old-fashioned flu shots , ” Weissman said .
While mRNA is getting a lot of attention , @ @ @ @ @ @ @ Inovio is developing a coronavirus vaccine that uses a double-stranded ring of DNA known as a plasmid .
It requires a hand-held device to induce an electric current near the injection site , causing pores within the cell to open , which allows the plasmid to enter .
The instructions in the plasmid can then be used to make viral proteins .
The company expects to start phase 3 trials in September .
The other new vaccine platform technology for Covid-19 is the adenovirus vector .
This is the approach companies such as @ @ @ @ @ @ @ using for their vaccines .
It ’ s also the basis for the famous vaccine candidate from Oxford University ’ s Jenner Institute , which is being developed with AstraZeneca and is now in phase 3 clinical trials .
The Russian government announced this week that it has an adenovirus vector vaccine for Covid-19 , too .
Dubbed Sputnik V , the vaccine has been registered for use , though many researchers outside of Russia are concerned that the vaccine gained approval without going through the full battery of clinical trials .
Adenoviruses @ @ @ @ @ @ @ cause mild illnesses with symptoms resembling those of a common cold or influenza , though an infection can be dangerous for people who have compromised immune systems or certain preexisting conditions .
“ This suggests that they are less pathogenic and they can inherently induce protective immunity through nasal routes for respiratory infections , ” University of Alberta Faculty of Medicine and Dentistry professor Babita Agrawal , who studies the immune system , said in an email .
“ Therefore , a vaccine based on [ an adenovirus vector ] could be certainly @ @ @ @ @ @ @ The virus itself is usually less than 100 nanometers in diameter and shaped like an icosahedron — a 20-sided shape with triangle faces , similar to D20 dice .
At its corners , it has fibers that stick out .
The adenovirus is very efficient at getting into cells .
Researchers have experimented with the adenovirus for years as a tool for gene therapy but are now applying it to vaccines .
Scientists figured out they could modify the virus to harness its breaking-and-entering skills without causing an infection .
Instead , the @ @ @ @ @ @ @ material inside a cell , serving as a vector .
In the case of Covid-19 , researchers are again looking at getting the instructions for making the spike protein of SARS-CoV-2 into the cell .
The way it works is that researchers take the genome of the adenovirus and cut out the section that allows it to reproduce .
Then they splice in a section of DNA that codes for the spike protein , turning the adenovirus into a recombinant vector .
Because the adenovirus is a DNA virus , it has to @ @ @ @ @ @ @ a cell but into the cell ’ s nucleus .
“ It goes into the nucleus , but it does not insert into the genome , ” said Hildegund C.J .
Ertl , a professor at the Wistar Institute ’ s Vaccine & Immunotherapy Center .
“ It ’ s a fairly transient effect.
” Once in the nucleus , the DNA coding for the spike protein is transcribed into mRNA and then transported out of the nucleus into the cell ’ s cytoplasm , where it ’ s translated into protein .
@ @ @ @ @ @ @ t reproduce , how do scientists make more of them ?
William Wold , chair of the molecular microbiology and immunology department at the Saint Louis University School of Medicine , explained that recombinant viruses are cultured in cell lines that provide the missing hardware to allow them to make copies of themselves .
“ It ’ s easy to make large batches of the virus , ” said Wold .
But without these engineered cells , the virus can ’ t spread .
However , there are some drawbacks .
Because versions @ @ @ @ @ @ @ there are many people who have immunity .
To get around this , groups like the team at Oxford are using a chimpanzee adenovirus as a vector , which is different enough from human adenoviruses that most people ’ s immune systems won ’ t react to it right away .
But once a vaccine is delivered using a chimpanzee adenovirus , it ’ s likely that many people would develop immunity to the new vector .
That would make it difficult to use the same platform again for another vaccine .
The @ @ @ @ @ @ @ same hurdles as conventional approaches : Phase 3 clinical trials and manufacturing While new vaccine approaches have helped speed up early development , they are now entering phase 3 trials , where tens of thousands of people are randomly selected to receive either the vaccine or a placebo .
Simply recruiting enough suitable participants can take weeks .
Many vaccine candidates , including those using the new platforms , require two doses , often several weeks apart .
Concluding the trials depends on waiting and seeing how the virus spreads among those who @ @ @ @ @ @ @ ’ t .
That can take months .
“ The one thing you can ’ t truncate are these phase 3 trials , ” Paul Offit , director of the Vaccine Education Center at the Children ’ s Hospital of Philadelphia , told reporters during the National Press Foundation webinar .
“ The proof is in the pudding .
Phase 3 is the pudding.
” The main challenge will be demonstrating that the vaccines actually provide protection against the coronavirus .
In clinical trials , researchers have found that both mRNA and adenovirus @ @ @ @ @ @ @ to the virus and trigger a response from immune cells .
Those are good signs , but they don ’ t guarantee that the vaccine recipient is shielded from infection .
For Covid-19 , the specific combination of responses from the body that indicate whether someone is immune to the virus remains unknown .
This combination is called the correlate of protection , or the correlate of immunity .
Without knowing the correlate of protection for Covid-19 , researchers can find out if a vaccine is effective only when it ’ s tested @ @ @ @ @ @ @ waiting to see how vaccinated people respond when they ’ re exposed .
Phase 3 trials also provide an important final safety check .
Most side effects related to these new vaccine platforms — fever , muscle pain , soreness , chills — have been pretty minor in early clinical trials .
But more significant and less-frequent complications could emerge during large-scale testing , when people with imperfect health or preexisting conditions start receiving the vaccines .
It ’ s important to ensure that such problems are rare , since a Covid-19 vaccine @ @ @ @ @ @ @ billions of people .
If a new vaccine platform does get approval , making enough vaccines will be the next challenge .
The world has decades of experience producing conventional vaccines , but companies are still learning how to manufacture the new platforms in large quantities .
“ The starting line is a little further back .
We don ’ t have the reassurance from the widespread use of the same technology in a different vaccine , ” said Jesse Goodman , a professor of medicine at Georgetown University and former chief scientist @ @ @ @ @ @ @ “ For example , when we had the 2009 [ H1N1 ] influenza pandemic , those vaccines were made using the technology and facilities and manufacturing processes that we used every year for flu vaccines.
” It ’ s one thing to make small batches of an mRNA or adenovirus vaccine in a laboratory .
It ’ s quite a different endeavor to make billions of doses on multiple assembly lines in different parts of the world .
Such large-scale production would need a global supply chain and validation to ensure that the @ @ @ @ @ @ @ infrastructure has yet to be built .
And since the majority of the world remains vulnerable to the disease , any coronavirus vaccine will need to be deployed on a much larger scale than existing vaccines in order to limit the spread of the virus .
That ’ s pushing governments and institutions to take some unprecedented steps to prepare .
“ The one thing that ’ s happened with this vaccine that I ’ ve never seen happen before is that pharmaceutical companies have already started making vaccines for people , even @ @ @ @ @ @ @ yet , ” Weissman said .
But there ’ s still no guarantee that any coronavirus vaccine will come to fruition .
The first vaccine across the line may not be the best one ; multiple vaccines for different population subsets , such as the elderly , will likely be needed .
So even if an mRNA vaccine or adenovirus vaccine for Covid-19 gains approval , it may be prudent to continue pursuing a conventional vaccine as well .
And vaccines alone are not enough .
Ending the Covid-19 pandemic will still demand @ @ @ @ @ @ @ of people are vaccinated to create herd immunity .
Although the timing of when a phase 3 trial for a Covid-19 vaccine might conclude is largely out of our hands , we can set the stage for the end of the pandemic now by limiting the spread of this deadly disease .
Will you become our 20,000th supporter ?
When the economy took a downturn in the spring and we started asking readers for financial contributions , we weren ’ t sure how it would go .
Today , we ’ re humbled @ @ @ @ @ @ @ chipped in .
The reason is both lovely and surprising : Readers told us that they contribute both because they value explanation and because they value that other people can access it , too .
We have always believed that explanatory journalism is vital for a functioning democracy .
That ’ s never been more important than today , during a public health crisis , racial justice protests , a recession , and a presidential election .
But our distinctive explanatory journalism is expensive , and advertising alone won ’ t let us @ @ @ @ @ @ @ volume this moment requires .
Your financial contribution will not constitute a donation , but it will help keep Vox free for all .
Contribute today from as little as $ 3 .

As urgency mounts for a Covid-19 coronavirus vaccine, a key question for scientists is whether this pandemic will be the watershed moment for two new technologies that have never before seen widespread use in humans. If proven effective, these approaches could dramatically speed up the development of other new vaccines and drastically lower costs, heralding a new era in the fight against infectious disease.
The main technologies gaining traction are vaccines that use an adenovirus vector and mRNA. Rather than construct a new vaccine from scratch, the idea behind these technologies is to use a standard set of parts, like a repurposed virus or a nanoparticle, to carry genetic material into a cell. That material — DNA or RNA — can then code for specific proteins from a virus.
Once one of these delivery platforms are proven safe, it’s just a matter of tweaking DNA and RNA strands. That’s much faster than conventional vaccines, which involve culturing large quantities of viruses that are then weakened, inactivated, or separated into tiny fragments and purified — processes that require years of cumbersome trial-and-error and safety testing.
“If the new platforms work in a way, that may actually change how other vaccines are produced,” Rahul Gupta, senior vice president and chief medical and health officer at the March of Dimes, told reporters during a National Press Foundation webinar on August 7. “So we may be at the cusp of very much a new technology that we’re going to see for the first time in over a century, basically.”
Researchers using these new platforms have recently posted some encouraging results. On Thursday, the pharmaceutical giant Pfizer published results of its phase 1 and phase 2 clinical trials for its mRNA-based vaccine platform in the journal Nature. Moderna is now entering phase 3 trials for its mRNA platform for Covid-19.
Meanwhile, Oxford University’s Jenner Institute is partnering with AstraZeneca to develop a vaccine using an adenovirus vector platform. It has also published some early promising results.
But there is a lot of competition, with more than 200 coronavirus vaccine candidates under investigation around the world. Two dozen are undergoing testing in humans, and six are in phase 3 clinical trials as of August 13.
A vaccine effort of this scale is astonishing for a disease that was discovered less than a year ago. But the immense health and economic devastation of the Covid-19 pandemic has prompted an unprecedented level of collaboration among scientists, as well as funding from governments, private companies, and philanthropists. That’s why some scientists expect there will be enough data proving the safety and efficacy of a Covid-19 vaccine in record time, possibly by the end of the year or early 2021. An effective, widely available vaccine would be a major step toward ending the pandemic.
However, there is no guarantee that any of these candidates will succeed, let alone whether a new vaccine technology will triumph over tried-and-true methods. Although companies working with the new platforms have readily cleared the earlier stages of clinical trials, they are now at the mercy of larger, slower phase 3 trials, where a lot can happen to derail their progress.
That’s why it’s important to understand how these novel strategies for preventing infection work, what they bring to the table, and the critical caveats to consider.
How most older vaccines work
Vaccines work by coaching the immune system to fight off a specific pathogen. When you get one, your white blood cells are being introduced to a potential threat, such as a virus or bacterium. That gives the immune system time to start mounting a response so that if the pathogen shows up another time, the body can quickly neutralize it.
Vaccines have been around in various forms for centuries, but the 20th century saw a boom in new ones for diseases such as polio, anthrax, pneumonia, meningitis, Hepatitis A, and influenza.
The conventional strategies for constructing vaccines that offer strong, long-lasting immunity involve mimicking the target. One of the most effective ways to do this is with a live attenuated vaccine. Here, a live form of the virus or bacterium is cultivated in such a way that it is weakened when given to a human. The pathogen can reproduce somewhat, but rarely enough to make the recipient sick. The most common vaccines — against smallpox, measles, mumps, and rubella — use live attenuated viruses.
Vaccines can also target toxic products of a bacterium or virus. Toxoid vaccines, like those for diphtheria and tetanus, are stable and safe but often require multiple doses.
Another approach is to use an inactivated version of the pathogen, usually a live pathogen that has been deliberately killed by heat or with a chemical treatment. This is the approach behind vaccines for diseases like Hepatitis A and rabies. Inactivated pathogen vaccines also often require more than one dose or boosters to retain immunity.
But instead of using whole-virus or bacterium particles, scientists can also use purified fragments of a pathogen — known as antigens — to trigger an immune reaction. These subunit vaccines tend to be stable, but they’re tricky to do right and often generate a weaker immune response than whole-pathogen vaccines.
Developing a vaccine using any of these methods, however, is time-consuming, often taking more than a decade to demonstrate that they’re safe and effective. That’s far too long during a pandemic like the one sweeping the world right now.
The new Covid-19 vaccine platforms harness human cells to make key components
Both mRNA vaccines and adenovirus vector vaccines build on the idea of a subunit vaccine. In the case of SARS-CoV-2, the virus that causes Covid-19, the most common subunit of interest is the spike protein.
This protein is the business end of the virus. It’s what the coronavirus uses to dock with the ACE2 receptor on a human cell in order to enter the cell, make copies of itself, and then spread to other cells.
Scientists reason that they can coax the immune system to generate antibodies to this spike protein. Antibodies are proteins made by the immune system that attach to specific parts of a pathogen, thereby disabling it or marking it for destruction by other immune cells. If antibodies bind to the spike protein of a live SARS-CoV-2 virus, they could prevent it from causing an infection.
But with these new platforms, it’s not the spike protein of the virus that’s being injected, it’s the genetic instructions for making it. The main differences between mRNA vaccines and adenovirus vector vaccines are the genetic material they use and how they get it into the cell. The mRNA vaccines use mRNA, while adenovirus vaccines use DNA.
Once the instructions are inside the cell, the cell’s machinery reads them to manufacture the spike protein of the virus. The newly minted spike proteins are either secreted from the cell or attached to its surface, where other cells from the immune system can identify the spike protein and begin manufacturing antibodies to it.
The process ends up not only mimicking a key structure of the virus but also imitating how the virus works during an infection, which could potentially generate a stronger immune response and yield better protection compared with other approaches. And because these proteins are produced from within cells rather than injected from the outside, they may be less likely to provoke adverse reactions in the recipient.
How mRNA vaccines work
On August 11, President Donald Trump announced that the US government would buy 100 million doses of Moderna’s mRNA coronavirus vaccine in a deal valued at $1.53 billion, bringing the country’s total investment in the company to $2.48 billion. (The Department of Health and Human Services previously said it would buy 100 million doses of Pfizer’s mRNA vaccine.)
These are just a couple of the big bets the federal government has placed on different vaccine manufacturers, but the fact that it’s investing so much in a new approach like mRNA signals how much promise it holds.
mRNA stands for messenger ribonucleic acid. It’s a molecule that’s copied from DNA in a cell’s nucleus and used as the code for making a specific protein. If you think of the DNA in the nucleus as a giant cookbook containing all the recipes for all the meals you’ll ever eat, mRNA is the notecard you use to jot down instructions for making your favorite banana bread.
Compared to DNA, mRNA is shorter in length, less stable, and designed to be disposable. Your cells are making and breaking down mRNA strands all the time.
With an mRNA vaccine, the idea is to get a segment of mRNA that codes for a specific viral protein into a cell. For vaccine developers, that means that instead of going through the tedious process of isolating and purifying subunits of a virus, they can just change the code in a strand of mRNA. That makes the development process much faster than conventional approaches, which can take months or years.
“mRNA can literally be completed in days to weeks to create a brand-new vaccine,” said Drew Weissman, a professor of medicine at the University of Pennsylvania. He noted that it took only 66 days from when the genome of the SARS-CoV-2 virus was sequenced to when the first patient was injected with an mRNA-based Covid-19 vaccine.
One of the challenges with using mRNA is that your body can perceive it as a threat, as many viruses use RNA to encode their genomes. There are a lot of enzymes in the body that can readily digest RNA before it gets into a cell. (There are even RNA-digesting enzymes on your skin.) Free-floating mRNA strands in the body can trigger inflammation, so to shield the mRNA until it gets into a cell, developers encase it inside a lipid nanoparticle — a tiny oil bubble. The RNA strand itself is also modified to make it less inflammatory.
Once the mRNA is coded, modified, and encapsulated, it can then be injected. “All modified RNA vaccines for Covid are given intramuscularly, just like old-fashioned flu shots,” Weissman said.
While mRNA is getting a lot of attention, similar approaches are also undergoing tests. Inovio is developing a coronavirus vaccine that uses a double-stranded ring of DNA known as a plasmid. It requires a hand-held device to induce an electric current near the injection site, causing pores within the cell to open, which allows the plasmid to enter. The instructions in the plasmid can then be used to make viral proteins. The company expects to start phase 3 trials in September.
How recombinant adenovirus vector vaccines work
The other new vaccine platform technology for Covid-19 is the adenovirus vector. This is the approach companies such as CanSino Biologics and Johnson & Johnson are using for their vaccines. It’s also the basis for the famous vaccine candidate from Oxford University’s Jenner Institute, which is being developed with AstraZeneca and is now in phase 3 clinical trials.
The Russian government announced this week that it has an adenovirus vector vaccine for Covid-19, too. Dubbed Sputnik V, the vaccine has been registered for use, though many researchers outside of Russia are concerned that the vaccine gained approval without going through the full battery of clinical trials.
Adenoviruses are a family of viruses that usually cause mild illnesses with symptoms resembling those of a common cold or influenza, though an infection can be dangerous for people who have compromised immune systems or certain preexisting conditions.
“This suggests that they are less pathogenic and they can inherently induce protective immunity through nasal routes for respiratory infections,” University of Alberta Faculty of Medicine and Dentistry professor Babita Agrawal, who studies the immune system, said in an email. “Therefore, a vaccine based on [an adenovirus vector] could be certainly a good vaccine candidate against SARS-CoV-2.”
The virus itself is usually less than 100 nanometers in diameter and shaped like an icosahedron — a 20-sided shape with triangle faces, similar to D20 dice. At its corners, it has fibers that stick out.
The adenovirus is very efficient at getting into cells. Researchers have experimented with the adenovirus for years as a tool for gene therapy but are now applying it to vaccines.
Scientists figured out they could modify the virus to harness its breaking-and-entering skills without causing an infection. Instead, the virus can deliver a piece of genetic material inside a cell, serving as a vector.
In the case of Covid-19, researchers are again looking at getting the instructions for making the spike protein of SARS-CoV-2 into the cell.
The way it works is that researchers take the genome of the adenovirus and cut out the section that allows it to reproduce. Then they splice in a section of DNA that codes for the spike protein, turning the adenovirus into a recombinant vector.
Because the adenovirus is a DNA virus, it has to get its genetic material not just into a cell but into the cell’s nucleus.
“It goes into the nucleus, but it does not insert into the genome,” said Hildegund C.J. Ertl, a professor at the Wistar Institute’s Vaccine & Immunotherapy Center. “It’s a fairly transient effect.”
Once in the nucleus, the DNA coding for the spike protein is transcribed into mRNA and then transported out of the nucleus into the cell’s cytoplasm, where it’s translated into protein.
So if the modified virus can’t reproduce, how do scientists make more of them? William Wold, chair of the molecular microbiology and immunology department at the Saint Louis University School of Medicine, explained that recombinant viruses are cultured in cell lines that provide the missing hardware to allow them to make copies of themselves. “It’s easy to make large batches of the virus,” said Wold. But without these engineered cells, the virus can’t spread.
However, there are some drawbacks. Because versions of the adenovirus spread in humans, there are many people who have immunity. To get around this, groups like the team at Oxford are using a chimpanzee adenovirus as a vector, which is different enough from human adenoviruses that most people’s immune systems won’t react to it right away.
But once a vaccine is delivered using a chimpanzee adenovirus, it’s likely that many people would develop immunity to the new vector. That would make it difficult to use the same platform again for another vaccine.
The new Covid-19 vaccine platforms still face the same hurdles as conventional approaches: Phase 3 clinical trials and manufacturing
While new vaccine approaches have helped speed up early development, they are now entering phase 3 trials, where tens of thousands of people are randomly selected to receive either the vaccine or a placebo. Simply recruiting enough suitable participants can take weeks. Many vaccine candidates, including those using the new platforms, require two doses, often several weeks apart. Concluding the trials depends on waiting and seeing how the virus spreads among those who received the vaccine and those who didn’t. That can take months.
“The one thing you can’t truncate are these phase 3 trials,” Paul Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, told reporters during the National Press Foundation webinar. “The proof is in the pudding. Phase 3 is the pudding.”
The main challenge will be demonstrating that the vaccines actually provide protection against the coronavirus. In clinical trials, researchers have found that both mRNA and adenovirus vaccines can make the body produce antibodies to the virus and trigger a response from immune cells.
Those are good signs, but they don’t guarantee that the vaccine recipient is shielded from infection. For Covid-19, the specific combination of responses from the body that indicate whether someone is immune to the virus remains unknown. This combination is called the correlate of protection, or the correlate of immunity.
Without knowing the correlate of protection for Covid-19, researchers can find out if a vaccine is effective only when it’s tested against the actual virus. That means waiting to see how vaccinated people respond when they’re exposed.
Phase 3 trials also provide an important final safety check. Most side effects related to these new vaccine platforms — fever, muscle pain, soreness, chills — have been pretty minor in early clinical trials. But more significant and less-frequent complications could emerge during large-scale testing, when people with imperfect health or preexisting conditions start receiving the vaccines. It’s important to ensure that such problems are rare, since a Covid-19 vaccine would potentially have to be given to billions of people.
If a new vaccine platform does get approval, making enough vaccines will be the next challenge. The world has decades of experience producing conventional vaccines, but companies are still learning how to manufacture the new platforms in large quantities.
“The starting line is a little further back. We don’t have the reassurance from the widespread use of the same technology in a different vaccine,” said Jesse Goodman, a professor of medicine at Georgetown University and former chief scientist at the Food and Drug Administration. “For example, when we had the 2009 [H1N1] influenza pandemic, those vaccines were made using the technology and facilities and manufacturing processes that we used every year for flu vaccines.”
It’s one thing to make small batches of an mRNA or adenovirus vaccine in a laboratory. It’s quite a different endeavor to make billions of doses on multiple assembly lines in different parts of the world. Such large-scale production would need a global supply chain and validation to ensure that the facilities provide a consistent product. That infrastructure has yet to be built.
And since the majority of the world remains vulnerable to the disease, any coronavirus vaccine will need to be deployed on a much larger scale than existing vaccines in order to limit the spread of the virus.
That’s pushing governments and institutions to take some unprecedented steps to prepare. “The one thing that’s happened with this vaccine that I’ve never seen happen before is that pharmaceutical companies have already started making vaccines for people, even if they haven’t been approved yet,” Weissman said.
But there’s still no guarantee that any coronavirus vaccine will come to fruition. The first vaccine across the line may not be the best one; multiple vaccines for different population subsets, such as the elderly, will likely be needed. So even if an mRNA vaccine or adenovirus vaccine for Covid-19 gains approval, it may be prudent to continue pursuing a conventional vaccine as well.
And vaccines alone are not enough. Ending the Covid-19 pandemic will still demand measures like social distancing until sufficient numbers of people are vaccinated to create herd immunity. Although the timing of when a phase 3 trial for a Covid-19 vaccine might conclude is largely out of our hands, we can set the stage for the end of the pandemic now by limiting the spread of this deadly disease.
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