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Read an Oxford Team Immunologist Explain ChAdOx1 Vaccine Trial Results

Oxford immunologist on coronavirus vaccine: our early results look highly promising

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3 years ago

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This article was originally published by The Conversation.

 
A vaccine against COVID-19 is urgently needed if we’re to stop the virus spreading and prevent potentially millions of further deaths. We’re now one step closer to that goal. Today, we published early results from our clinical trial of the vaccine ChAdOx1 nCoV-19 (also known as AZD1222), designed by the University of Oxford and developed in partnership with AstraZeneca. The preliminary data shows that it is safe and induced a strong antibody response in all vaccinated volunteers, suggesting that an effective vaccine could be within reach. This trial was the first time that the vaccine had been given to humans: 543 healthy adults aged 18-55 were vaccinated with a single dose of ChAdOx1 nCoV-19. A further 534 people were given a control vaccine that gives similar minor reactions, including injection site redness and mild pain. Volunteers are having their immune response (both antibodies and T cell levels) monitored for at least 12 months, and will also be observed to see whether or not they develop COVID-19. The preliminary data from the trial clearly demonstrates that the vaccine induces an antibody response within 28 days. This response is in a similar range to that in individuals who have recovered from COVID-19, providing encouragement that the vaccine will be able to protect the majority of people against infection. Ten volunteers were also given a second “booster” dose of the vaccine. This increased the antibody response to even higher levels, and 100% of blood samples from this group showed neutralising activity against COVID-19 infection in a laboratory setting. The vaccine also induced T cells that specifically recognise SARS-CoV-2, the virus that causes COVID-19. It’s encouraging to see both antibody and T cell responses, as together this is the right kind of immune response that could lead to protection against the virus. Importantly, the vaccine demonstrates an acceptable safety profile, with no vaccine-induced severe adverse events – that is, no major side-effects. We were confident testing the vaccine in humans after encouraging trials with mice and rhesus macaque monkeys. These had shown that the vaccine was safe and induced a robust immune response. Significantly, the vaccinated monkeys were protected from severe disease after they were challenged with a much higher dose of SARS-CoV-2 than humans would encounter through natural exposure.

How does this vaccine work?

Vaccines work by training the immune system to recognise and fight off infectious agents (pathogens), such as bacteria and viruses. Vaccines do this by presenting the immune system with a readily identifiable part of a pathogen, which the immune system remembers so that it can quickly respond should it encounter that same pathogen in the future. Most vaccines in development for SARS-CoV-2 – including this one – focus on presenting the spike protein that decorates the surface of the virus. It’s this protein that allows the virus into human cells by binding to a molecule on their surface called ACE2.
Illustration of the SARS-CoV-2, showing the spike proteins on its surface
The coronavirus SARS-CoV-2, with its spike proteins shown in red. US Centers for Disease Control and Prevention/Wikimedia Commons
There is a broad range of approaches to vaccine design; ChAdOx1 nCoV-19 is what’s known as a viral vector vaccine. To make this vaccine, particles of a different, harmless virus (called ChAdOx1) are loaded with the portion of SARS-CoV-2 DNA that instructs cells how to build the spike protein. When these ChAdOx1 particles infect human cells, the coronavirus DNA is then “expressed”, building the spike protein for the immune system to respond to. Importantly for vaccine safety, the viral vector can’t replicate and cause an ongoing infection. The ChAdOx1 viral vector has been used to make eight vaccines already in clinical trials for other human diseases, including Mers (Middle Eastern respiratory syndrome), a coronavirus that is related to SARS-CoV-2.

What happens now?

Crucially, we need to demonstrate that the vaccine is effective – that it results in significantly lower (ideally zero) cases of COVID-19 in the ChAdOx1 nCoV-19 vaccinated group versus the control group. Falling infection rates in the UK are an excellent outcome for the health of the nation, but may compromise the ability to show this. If there are no cases of COVID-19 in the group receiving the control vaccine, comparing that group to the vaccinated group would be meaningless. Deliberately infecting people with the virus may be possible in future (after careful consideration of the ethical implications), but is not currently allowed. For this reason, a second trial has been launched in approximately 10,000 UK individuals, focusing on health workers, and further trials are being conducted in Brazil and South Africa, where infection rates are much higher. The expanded UK trial will include children and older adults to estimate vaccine efficacy in these age groups. Immune responses in people over 70 are often lower than those in younger adults. It’s essential to follow the vaccine-induced immune response over a period of at least one year, to estimate whether booster injections will be required, and if so how often. My personal prediction – based on decreases in antibody levels in individuals infected with other types of coronavirus, rather than data from the current vaccine trial – is that we’re likely to need yearly boosters, similar to annual flu jabs. Finally, if the vaccine proves effective, rapid manufacture of potentially billions of doses would be required to supply the world. To facilitate this, AstraZeneca has already initiated a large-scale vaccine manufacturing programme, aiming to have hundreds of millions of doses with delivery starting by the end of 2020. Agreements are in place to provide the vaccine to low-income and middle-income countries and also to the UK, Europe and the US.

Rebecca Ashfield consults for SpyBiotech Ltd and OSI (Oxford Science Innovation) although these organisations will not benefit from this article. She is CSO of Ducentis Biotherapeutics Ltd, which develops novel therapies for autoimmune diseases and inflammation.

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International

Fighting the Surveillance State Begins with the Individual

It’s a well-known fact at this point that in the United States and most of the so-called free countries that there is a robust surveillance state in…

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7 hours ago

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October 23, 2023

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It’s a well-known fact at this point that in the United States and most of the so-called free countries that there is a robust surveillance state in place, collecting data on the entire populace. This has been proven beyond a shadow of a doubt by people like Edward Snowden, a National Security Agency (NSA) whistleblower who exposed that the NSA was conducting mass surveillance on US citizens and the world as a whole. The NSA used applications like those from Prism Systems to piggyback on corporations and the data collection their users had agreed to in the terms of service. Google would scan all emails sent to a Gmail address to use for personalized advertising. The government then went to these companies and demanded the data, and this is what makes the surveillance state so interesting. Neo-Marxists like Shoshana Zuboff have dubbed this “surveillance capitalism.” In China, the mass surveillance is conducted at a loss. Setting up closed-circuit television cameras and hiring government workers to be a mandatory editorial staff for blogs and social media can get quite expensive. But if you parasitically leech off a profitable business practice it means that the surveillance state will turn a profit, which is a great asset and an even greater weakness for the system. You see, when that is what your surveillance state is predicated on you’ve effectively given your subjects an opt-out button. They stop using services that spy on them. There is software and online services that are called “open source,” which refers to software whose code is publicly available and can be viewed by anyone so that you can see exactly what that software does. The opposite of this, and what you’re likely already familiar with, is proprietary software. Open-source software generally markets itself as privacy respecting and doesn’t participate in data collection. Services like that can really undo the tricky situation we’ve found ourselves in. It’s a simple fact of life that when the government is given a power—whether that be to regulate, surveil, tax, or plunder—it is nigh impossible to wrestle it away from the state outside somehow disposing of the state entirely. This is why the issue of undoing mass surveillance is of the utmost importance. If the government has the power to spy on its populace, it will. There are people, like the creators of The Social Dilemma, who think that the solution to these privacy invasions isn’t less government but more government, arguing that data collection should be taxed to dissuade the practice or that regulation needs to be put into place to actively prevent abuses. This is silly to anyone who understands the effect regulations have and how the internet really works. You see, data collection is necessary. You can’t have email without some elements of data collection because it’s simply how the protocol functions. The issue is how that data is stored and used. A tax on data collection itself will simply become another cost of doing business. A large company like Google can afford to pay a tax. But a company like Proton Mail, a smaller, more privacy-respecting business, likely couldn’t. Proton Mail’s business model is based on paid subscriptions. If there were additional taxes imposed on them, it’s possible that they would not be able to afford the cost and would be forced out of the market. To reiterate, if one really cares about the destruction of the surveillance state, the first step is to personally make changes to how you interact with online services and to whom you choose to give your data.

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International

Stock Market Today: Stocks turn higher as Treasury yields retreat; big tech earnings up next

A pullback in Treasury yields has stocks moving higher Monday heading into a busy earnings week and a key 2-year bond auction later on Tuesday.

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7 hours ago

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October 23, 2023

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Updated at 11:52 am EDT U.S. stocks turned higher Monday, heading into the busiest earnings week of the year on Wall Street, amid a pullback in Treasury bond yields that followed the first breach of 5% for 10-year notes since 2007. Investors, however, continue to track developments in Israel's war with Hamas, which launched its deadly attack from Gaza three weeks ago, as leaders around the region, and the wider world, work to contain the fighting and broker at least a form of cease-fire. Humanitarian aid is also making its way into Gaza, through the territory's border with Egypt, as officials continue to work for the release of more than 200 Israelis taken hostage by Hamas during the October 7 attack. Those diplomatic efforts eased some of the market's concern in overnight trading, but the lingering risk that regional adversaries such as Iran, or even Saudi Arabia, could be drawn into the conflict continues to blunt risk appetite. Still, the U.S. dollar index, which tracks the greenback against a basket of six global currencies and acts as the safe-haven benchmark in times of market turmoil, fell 0.37% in early New York trading 105.773, suggesting some modest moves into riskier assets. The Japanese yen, however, eased past the 150 mark in overnight dealing, a level that has some traders awaiting intervention from the Bank of Japan and which may have triggered small amounts of dollar sales and yen purchases. In the bond market, benchmark 10-year note yields breached the 5% mark in overnight trading, after briefly surpassing that level late last week for the first time since 2007, but were last seen trading at 4.867% ahead of $141 billion in 2-year, 5-year and 7-year note auctions later this week. Global oil prices were also lower, following two consecutive weekly gains that has take Brent crude, the global pricing benchmark, firmly past $90 a barrel amid supply disruption concerns tied to the middle east conflict. Brent contracts for December delivery were last seen $1.06 lower on the session at $91.07 per barrel while WTI futures contract for the same month fell $1.36 to $86.72 per barrel. Market volatility gauges were also active, with the CBOE Group's VIX index hitting a fresh seven-month high of $23.08 before easing to $20.18 later in the session. That level suggests traders are expecting ranges on the S&P 500 of around 1.26%, or 53 points, over the next month. A busy earnings week also indicates the likelihood of elevated trading volatility, with 158 S&P 500 companies reporting third quarter earnings over the next five days, including mega cap tech names such as Google parent Alphabet  (GOOGL) - Get Free Report, Microsoft  (MSFT) - Get Free Report, retail and cloud computing giant Amazon  (AMZN) - Get Free Report and Facebook owner Meta Platforms  (META) - Get Free Report. "It’s shaping up to be a big week for the market and it comes as the S&P 500 is testing a key level—the four-month low it set earlier this month," said Chris Larkin, managing director for trading and investing at E*TRADE from Morgan Stanley. "How the market responds to that test may hinge on sentiment, which often plays a larger-than-average role around this time of year," he added. "And right now, concerns about rising interest rates and geopolitical turmoil have the potential to exacerbate the market’s swings." Heading into the middle of the trading day on Wall Street, the S&P 500, which is down 8% from its early July peak, the highest of the year, was up 10 points, or 0.25%. The Dow Jones Industrial Average, which slumped into negative territory for the year last week, was marked 10 points lower while the Nasdaq, which fell 4.31% last week, was up 66 points, or 0.51%. In overseas markets, Europe's Stoxx 600 was marked 0.11% lower by the close of Frankfurt trading, with markets largely tracking U.S. stocks as well as the broader conflict in Israel. In Asia, a  slump in China stocks took the benchmark CSI 300 to a fresh 2019 low and pulled the region-wide MSCI ex-Japan 0.72% lower into the close of trading.
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Government

Forget Ron DeSantis: Walt Disney has a much bigger problem

The company’s political woes are a sideshow to the one key issue Bob Iger has to solve.

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7 hours ago

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October 23, 2023

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Walt Disney has a massive, but solvable, problem.

The company's current skirmishes with Florida Gov. DeSantis get a lot of headlines, but they're not having a major impact on the company's bottom line.

Related: What the Bud Light boycott means for Disney, Target, and Starbucks

DeSantis has made Walt Disney (DIS) - Get Free Report a target in what he calls his war on woke, an effort to win right-wing support as he tries to secure the Republican Party nomination for president. 

That effort has generated plenty of press and multiple lawsuits tied to the governor's takeover of the former Reedy Creek Improvement District, Disney's legislated self-governance operation. But it has not hurt revenue at the company's massive Florida theme-park complex.  

Disney Chief Executive Bob Iger addressed the matter during the company's third-quarter-earnings call, without directly mentioning DeSantis.

"Walt Disney World is still performing well above precovid levels: 21% higher in revenue and 29% higher in operating income compared to fiscal 2019," he said. 

And "following a number of recent changes we've implemented, we continue to see positive guest-experience ratings in our theme parks, including Walt Disney World, and positive indicators for guests looking to book future visits."

The theme parks are not Disney's problem. The death of the movie business is, however, a hurdle that Iger has yet to show that the company has a plan to clear.

Boba Fett starred in a show on Disney+.

Image source: Walt Disney

Disney needs a plan to monetize content 

In 2019 Walt Disney drew in more $11 billion in global box office, or $13 billion when you add in the former Fox properties it also owns. In that year seven Mouse House films crossed the billion-dollar threshold in theaters, according to data from Box Office Mojo.

This year, the company will struggle to reach half that and it has no billion-dollar films, with "Guardians of the Galaxy Vol. 3" closing its theatrical run at $845 million globally. 

(That's actually good for third place this year, as only "Barbie" and "The Super Mario Bros. Movie" have broken the billion-dollar mark and they may be the only two films to do that this year.)

In the precovid world Disney could release two Pixar movies, three Marvel films, a live-action remake of an animated classic, and maybe one other film that each would be nearly guaranteed to earn $1 billion at the box office.

That's simply not how the movie business works anymore. While theaters may remain part of Disney's plan to monetize its content, the past isn't coming back. Theaters may remain a piece of the movie-release puzzle, but 2023 isn't an anomaly or a bad release schedule.

Consumers have big TVs at home and they're more than happy to watch most films on them.

Disney owns the IP but charges too little

People aren't less interested in Marvel and Star Wars; they're just getting their fix from Disney+ at an absurdly low price. 

Over the past couple of months through the next few weeks, I will have watched about seven hours of premium Star Wars content and five hours of top-tier Marvel content with "Ahsoka" and "Loki" respectively. 

Before the covid pandemic, I gladly would have paid theater prices for each movie in those respective universes. Now, I have consumed about six movies worth of premium content for less than the price of two movie tickets.

By making its premium content television shows available on a service that people can buy for $7.99 a month Disney has devalued its most valuable asset, its intellectual property. 

Consumers have shown that they will pay the $10 to $15 cost of a movie ticket to see what happens next in the Marvel Cinematic Universe or the Star Wars galaxy. But the company has offered top-tier content from those franchises at a lower price.

Iger needs to find a way to replace billions of dollars in lost box office, but charging less for the company's content makes no sense. 

Now, some fans likely won't pay triple the price for Disney+. But if it were to bundle a direct-to-consumer ESPN along with content that currently gets released to movie theaters, Disney might create a package that it can price in a way that reflects the value of its IP.

Consumers want Disney's content and they will likely pay more for it. Iger simply has to find a way to make that happen.

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