What’s The Difference Between Covid-19 Coronavirus Vaccines

Coronavirus COVID-19 single dose small vials and multi dose in scientist hands concept. Research for new novel corona virus immunization drug.

The world can’t return to normal without safe and effective vaccines against the SARS-CoV-2 coronavirus along with a coordinated global vaccination programme.

Researchers have been racing to develop potential drugs that could help end the ongoing Covid-19 pandemic. There are currently around 200 vaccine candidates and about a quarter passed preclinical tests and are now undergoing clinical trials.

What’s the difference between the various candidate vaccines?

A pie chart of candidates can be cut several ways. One is to slice it into six uneven pieces according to the technology (or ‘platform’) that’s used to produce the drug. Those six technologies can be grouped into three broader categories: dead or disabled viruses, artificial vectors, and viral components.

Dead or disabled viruses

Traditional vaccines contain a dead or disabled virus, designed to be incapable of causing severe disease while also provoking an immune response that provides protection against the live virus.

1. Live-attenuated viruses

Attenuated means ‘weakened’. Weakening a live virus typically involves reducing its virulence — capacity to cause disease — or ability to replicate through genetic engineering. The virus still infects cells and causes mild symptoms.

For a live-attenuated virus, an obvious safety concern is that the virus might gain genetic changes that enable it to revert back to the more virulent strain. Another worry is that a mistake during manufacturing could produce a defective vaccine and cause a disease outbreak, which once happened with a polio vaccine. MORE FOR YOUJapan Has Opened Hayabusa2’s Capsule, Confirming It Contains Samples From Asteroid RyuguDonald Trump’s Presidency Will End On The Day Of A Comet, A Meteor Shower And A Total Eclipse Of The SunIn A New Epidemiological Study, Daily Doses Of Glucosamine/Chondroitin Are Linked To Lower All-Cause Mortality

But using a live-attenuated virus has one huge benefit: vaccination resembles natural infection, which usually leads to robust immune responses and a memory of the virus’ antigens that can last for many years.

Live-attenuated vaccines based on SARS-CoV-2 are still undergoing preclinical testing, developed by start-up Codagenix and the Serum Institute of India.

2. Inactivated viruses

Inactivated means ‘dead’ (‘inactivated’ is used because some scientists don’t consider viruses to be alive). The virus will be the one you want to create a vaccine against, such as SARS-CoV-2, which is usually killed with chemicals.

Two Chinese firms have developed vaccines that are being tested for safety and effectiveness in large-scale Phase III clinical trials: ‘CoronaVac’ (previously ‘PiCoVacc’) from Sinovac Biotech and ‘New Crown COVID-19’ from Sinopharm. Both drugs contain inactivated virus, didn’t cause serious adverse side-effects and prompted the immune system to produce antibodies against SARS-CoV-2.

Sinopharm’s experimental vaccine has reportedly been administered to hundreds of thousands of people in China, and both drugs are now being trialled in countries across Asia, South America and the Middle East.

COVID-19 vaccine landscape (left) and platforms for SARS-CoV-2 vaccine development (right)
The global COVID-19 vaccine landscape (left) and Vaccine platforms used for SARS-CoV-2 vaccine … [+] Springer

Artificial vectors

Another conventional approach in vaccine design is to artificially create a vehicle or ‘vector’ that can deliver specific parts of a virus to the adaptive immune system, which then learns to target those parts and provides protection.

That immunity is achieved by exposing your body to a molecule that prompts the system to generate antibodies, an antigen, which becomes the target of an immune response. SARS-CoV-2 vaccines aim to target the spike protein on the surface of coronavirus particles — the proteins that allows the virus to invade a cell.

3. Recombinant viruses

A recombinant virus is a vector that combines the target antigen from one virus with the ‘backbone’ from another — unrelated — virus. For SARS-CoV-2, the most common strategy is to put coronavirus spike proteins on an adenovirus backbone.

Recombinant viruses are a double-edged sword: they behave like live-attenuated viruses, so a recombinant vaccine comes with the potential benefits of provoking a robust response from the immune system but also potential costs from causing an artificial infection that might lead to severe symptoms.

A recombinant vaccine might not provoke an adequate immune response in people who have previously been exposed to adenoviruses that infect humans (some cause the common cold), which includes one candidate developed by CanSino Biologics in China and ‘Sputnik V’ from Russia’s Gamaleya National Research Centre — both of which are in Phase III clinical trials and are licensed for use in the military.

To maximize the chance of provoking immune responses, some vaccines are built upon viruses from other species, so humans will have no pre-existing immunity. The most high-profile candidate is ‘AZD1222’, better known as ‘ChAdOx1 nCoV-19’ or simply ‘the Oxford vaccine’ because it was designed by scientists at Oxford University, which will be manufactured by AstraZeneca. AZD1222 is based on a chimpanzee adenovirus and seems to be 70% effective at preventing Covid-19.

Some recombinant viruses can replicate in cells, others cannot — known as being ‘replication-competent’ or ‘replication-incompetent’. One vaccine candidate that contains a replicating virus, developed by pharmaceutical giant Merck, is based on Vesicular Stomatitis Virus (VSV), which infects guinea pigs and other pets.

4. Virus-like particles

A virus-like particle, or VLP, is a structure assembled from viral proteins. It resembles a virus but doesn’t contain the genetic material that would allow the VLP to replicate. For SARS-CoV-2, the VLP obviously includes the spike protein.

One coronavirus-like particle (Co-VLP) vaccine from Medicago has passed Phase I trials to test it’s safe and has entered Phase II to test that it’s effective.

While there are currently few VLPs being developed for Covid-19, the technology is well-established and has been used to produce commercial vaccines against human papillomavirus (HPV) and hepatitis B.

Viral components

All vaccines are ultimately designed to expose the immune system to parts of a virus, not the whole thing, so why not deliver just those parts? That’s the reasoning behind vaccines that only contain spike proteins or spike genes.

5. Proteins

Protein-based vaccines can consist of the full-length spike protein or the key part, the tip of the spike that binds the ACE2 receptor on the surface of a cell — ACE2 is the lock that a coronavirus picks in order to break into the cell.

Manufacturing vaccines containing the protein alone has a practical advantage: researchers don’t have to deal with live coronaviruses, which should be grown inside cells within a biosafety level-3 lab.

A vaccine against only part of the protein — a ‘subunit’ — will be more vulnerable to being rendered useless if random mutations alter the protein, known as ‘antigenic drift‘, but full-length proteins are harder to manufacture. The immune system can recognize either as an antigen.

One candidate vaccine based on protein subunits is ‘NVX-CoV2373’ from Novavax, where the spike subunits are arranged as a rosette structure. It’s similar to a vaccine that’s already been licensed for use, FluBlok, which contains rosettes of protein subunits from the influenza virus.

6. Nucleic acids

Nucleic-acid vaccines contain genetic material, either deoxyribonucleic acid or ribonucleic acid — DNA or RNA. In a coronavirus vaccine, the DNA or RNA carries genetic instructions for producing a spike protein, which is made within cells.

Those spike genes can be carried on rings of DNA called ‘plasmids’, which are easy to manufacture by growing them in bacteria. DNA provokes a relatively weak immune response, however, and can’t simply be injected inside the body — the vaccine must be administered using a special device to force DNA into cells. Four DNA-based candidates are in Phase I or II trials.

The two most famous nucleic-acid vaccines are the drugs being developed by pharmaceutical giant Pfizer, partnered with BioNTech, and Moderna. Pfizer’s ‘BNT162b2’ and Moderna’s ‘mRNA-1273’ both use ‘messenger RNA’ — mRNA — to carry the spike genes and are delivered into cells via a lipid nanoparticle (LNP). The two mRNA vaccines have completed Phase III trials and preliminary results suggests they’re over 90% effective at preventing Covid-19.

As the above examples show, not only there are many potential vaccines but also various approaches. And while some technologies have already provided promising results, it remains to be seen which will actually be able to defeat the virus.

Full coverage and live updates on the CoronavirusFollow me on Twitter or LinkedIn. Check out my website or some of my other work here

JV Chamary

JV Chamary

I’m a science communicator specialising in public engagement and outreach through entertainment, focusing on popular culture. I have a PhD in evolutionary biology and…

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TODAY

Dr. Ashish Jha, dean of Brown University’s School of Public Health, joins the 3rd hour of TODAY to break down the differences between Moderna’s and Pfizer’s coronavirus vaccine candidates. He also comments on speculation of another national shutdown and whether families should still get together over Thanksgiving. » Subscribe to TODAY: http://on.today.com/SubscribeToTODAY » Watch the latest from TODAY: http://bit.ly/LatestTODAY About: TODAY brings you the latest headlines and expert tips on money, health and parenting. We wake up every morning to give you and your family all you need to start your day. If it matters to you, it matters to us. We are in the people business. Subscribe to our channel for exclusive TODAY archival footage & our original web series. Connect with TODAY Online! Visit TODAY’s Website: http://on.today.com/ReadTODAY Find TODAY on Facebook: http://on.today.com/LikeTODAY Follow TODAY on Twitter: http://on.today.com/FollowTODAY Follow TODAY on Instagram: http://on.today.com/InstaTODAY Follow TODAY on Pinterest: http://on.today.com/PinTODAY#COVID19Vaccines#AshishJha#TodayShow

Billionaire Eric Lefkofsky’s Tempus Raises $200 Million To Bring Personalized Medicine To New Diseases

On the surface, Eric Lefkofsky’s Tempus sounds much like every other AI-powered personalized medicine company. “We try to infuse as much data and technology as we can into the diagnosis itself,” Lefkofsky says, which could be said by the founder of any number of new healthcare companies.. But what makes Tempus different is that it is quickly branching out, moving from a focus on cancer to additional programs including mental health, infectious diseases, cardiology and soon diabetes. “We’re focused on those disease areas that are the most deadly,” Lefkofsky says. 

Now, the billionaire founder has an additional $200 million to reach that goal. The Chicago-based company announced the series G-2 round on Thursday, which includes a massive valuation of $8.1 billion. Lefkofsky, the founder of multiple companies including Groupon, also saw his net worth rise from the financing, from an estimated $3.2 billion to an estimated $4.2 billion.

Tempus is “trying to disrupt a very large industry that is very complex,” Lefkofsky says, “we’ve known it was going to cost a lot of money to see our business model to fruition.” 

In addition to investors Baillie Gifford, Franklin Templeton, Novo Holdings, and funds managed by T. Rowe Price, Lefkofsky, who has invested about $100 million of his own money into the company since inception, also contributed an undisclosed amount to the round. Google also participated as an investor, and Tempus says it will now store its deidentified patient data on Google Cloud. 

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“We are particularly attracted to companies that aim to solve fundamental and complex challenges within life sciences,” says Robert Ghenchev, a senior partner at Novo Holdings. “Tempus is, in many respects, the poster child for the kind of companies we like to support.” 

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Tempus, founded by Lefkofsky in 2015, is one of a new breed of personalized cancer diagnostic companies like Foundation Medicine and Guardant Health. The company’s main source of revenue comes from sequencing the genome of cancer patients’ tumors in order to help doctors decide which treatments would be most effective. “We generate a lot of molecular data about you as a patient,” Lefkofsky says. He estimates that Tempus has the data of about 1 in 3 cancer patients in the United States. 

But billing insurance companies for sequencing isn’t the only way the company makes money. Tempus also offers a service that matches eligible patients to clinical trials, and it licenses  de-identified patient data to other players in the oncology industry. That patient data, which includes images and clinical information, is “super important and valuable,” says Lefkofsky, who adds that such data sharing only occurs if patients consent. 

At first glance, precision oncology seems like a crowded market, but analysts say there is still plenty of room for companies to grow. “We’re just getting started in this market,” says Puneet Souda, a senior research analyst at SVB Leerink, “[and] what comes next is even larger.” Souda estimates that as the personalized oncology market expands from diagnostics to screening, another $30 billion or more will be available for companies to snatch up. And Tempus is already thinking ahead by moving into new therapeutic areas. 

While it’s not leaving cancer behind, Tempus has branched into other areas of precision medicine over the last year, including cardiology and mental health. The company now offers a service for psychiatrists to use a patient’s genetic information to determine the best treatments for major depressive disorder. 

In May, Lefkofsky also pushed the company to use its expertise to fight the coronavirus pandemic. The company now offers PCR tests for Covid-19, and has run over 1 million so far. The company also sequences other respiratory pathogens, such as the flu and soon pneumonia. As with cancer, Tempus will continue to make patient data accessible for others in the field— for a price. “Because we have one of the largest repositories of data in the world,” says Lefkofsky, “[it is imperative] that we make it available to anyone.” 

Lefkofsky plans to use capital from the latest funding round to continue Tempus’ expansion and grow its team. The company has hired about 700 since the start of the pandemic, he says, and currently has about 1,800 employees. He wouldn’t comment on exact figures, but while the company is not yet profitable he says Tempus has reached “significant scale in terms of revenue.” 

And why is he so sure that his company’s massive valuation isn’t over-inflated? “We benefit from two really exciting financial sector trends,” he says: complex genomic profiling and AI-driven health data. Right now, Lefkofsky estimates, about one-third of cancer patients have their tumors sequenced in three years. Soon, he says, that number will increase to two-thirds of patients getting their tumors sequenced multiple times a year. “The space itself is very exciting,” he says, “we think it will grow dramatically.” Follow me on Twitter. Send me a secure tip

Leah Rosenbaum

Leah Rosenbaum

I am the assistant editor of healthcare and science at Forbes. I graduated from UC Berkeley with a Master’s of Journalism and a Master’s of Public Health, with a specialty in infectious disease. Before that, I was at Johns Hopkins University where I double-majored in writing and public health. I’ve written articles for STAT, Vice, Science News, HealthNewsReview and other publications. At Forbes, I cover all aspects of health, from disease outbreaks to biotech startups.

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Eric Lefkofsky

To impact the nearly 1.7 million Americans who will be newly diagnosed with cancer this year, Eric Lefkofsky, co-founder and CEO of Tempus, discusses with Matter CEO Steven Collens how he is applying his disruptive-technology expertise to create an operating system to battle cancer. (November 29, 2016)

For access to live and exclusive video from CNBC subscribe to CNBC PRO: https://cnb.cx/2JdMwO7 » Subscribe to CNBC TV: https://cnb.cx/SubscribeCNBCtelevision » Subscribe to CNBC: https://cnb.cx/SubscribeCNBC » Subscribe to CNBC Classic: https://cnb.cx/SubscribeCNBCclassic Turn to CNBC TV for the latest stock market news and analysis. From market futures to live price updates CNBC is the leader in business news worldwide. Connect with CNBC News Online Get the latest news: http://www.cnbc.com/ Follow CNBC on LinkedIn: https://cnb.cx/LinkedInCNBC Follow CNBC News on Facebook: https://cnb.cx/LikeCNBC Follow CNBC News on Twitter: https://cnb.cx/FollowCNBC Follow CNBC News on Instagram: https://cnb.cx/InstagramCNBC

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Walmart Joins Pharmaceutical-Tracking Blockchain Consortium MediLedger

Big-box retail giant Walmart has joined MediLedger, a consortium building a blockchain for tracking the provenance of pharmaceuticals.

A spokeswoman for the Bentonville, Arkansas-based company confirmed Walmart’s participation to CoinDesk but had no further comment.

The move represents a deepening of Walmart’s involvement with blockchain technology. Separately, the retailer is a key participant in IBM’s Food Trust, a system for tracking fresh produce through the supply chain that’s built on the Hyperledger Fabric platform.

Walmart has insisted that its suppliers of leafy greens integrate the IBM blockchain, and it should bring similar supply-chain clout to MediLedger, whose members already include pharmaceutical manufacturers such as Pfizer and the three largest pharmaceutical wholesalers, McKesson, AmerisourceBergen, and Cardinal Health. 

“Health and wellness,” a category that includes pharmacy and over-the-counter drugs, accounted for $35 billion of Walmart’s U.S. sales in the fiscal year ended Jan. 31, or 10% of the total, according to the company’s annual report.

Unlike Food Trust, MediLedger uses an enterprise version of the ethereum blockchain, built with a modified version of the Parity client and a consensus mechanism called proof of authority. The consortium is spearheaded by San Francisco-based blockchain firm Chronicled, which closed a $16 million funding round earlier this year.

Walmart joins as MediLedger prepares to kick off a pilot project with the U.S. Food and Drug Administration (FDA) in early June. The agency is testing various approaches to creating an interoperable, digitized system for tracking and verifying prescription drugs, something Congress has mandated it deliver by 2023. 

Eric Garvin, co-lead of MediLedger, told CoinDesk:

“The pilots only really make sense if you are working with a group of collaborators.”

MediLedger initially focused on the verification of drugs that are returned to be resold – a sliver of the pharma market, but one that’s still worth over $6 billion. Legislation to help prevent fraudulent products being resold comes into effect in November of this year.

Now the expanded group will start work on the more broad-ranging tracking of all pharma products which involves interoperable data and packaging serialization.

Why blockchain?

It could be argued that in places like the U.K. where the healthcare system is largely run by the government, a digitized system like the one FDA has been mandated to create might be implemented more easily using a centralized system.  

But the U.S. is the largest privatized healthcare system in the world (with the highest prices), which makes for a sprawling fragmentation of siloed databases, supporting the case for a decentralized solution.

The Congressionally mandated 10-year roadmap to a standardized form of serialization on all drug packaging began with the very largest firms complying with electronic tracking of lot shipments, i.e. 100 boxes of some medicine at a time. The next goal was more granular serialization at the level of pillbox or bottle

The third plank of the legislation was that the data being gathered had to be technically interoperable.

That last requirement made some people in the industry think “blockchain is the perfect solution,” said Maria Palombini, director of communities and initiatives development for emerging technology at the IEEE Standards Association.

Palombini stressed that the FDA does not advocate one technology over another and its only prescription is the use of recognized standards within each pilot’s tech stacks.

However, making data (and metadata) interoperable presents the industry with a challenge, she said:

“I think some companies will try and embrace this, and some others will try and stay away from blockchain. Because there is one word that scares them – transparency.”

Garvin said nodes are distributed and operated by industry participants and technology providers, but that data privacy is being addressed with zero-knowledge proofs, a cryptographic method that allows someone to prove something is true about a set of data without exposing the data itself.

This data transparency question is especially pointed at the ends of the supply chain with large pharma dispensers like Walmart, who are unaccustomed to potentially sharing their sales data with competitors.

“They have to try and figure out a way to share this data give far more visibility into the inventory, but also now the retailers are going to have to give data back which they have never really been required to do so,” said Palombini. “That’s going to be a really hard part here.”

Walmart Pharmacy image via Shuttersto

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Source: Pivot – Blockchain Community

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