Apr 23, 2020

Axios Science

By Alison Snyder
Alison Snyder

Welcome to the first Axios Special Report about the science being used to tackle this pandemic — and prepare for future ones.

  • Over the next four weeks, we'll look at vaccines and treatments, the biology of viruses, and how science is intersecting with ethics and politics.
  • As a subscriber to Axios Science, Future or Vitals, you'll receive these reports.
  • Please send us your feedback. You can reach me at alison@axios.com, or hit reply to this email. Eileen is at eileen@axios.com, and Miriam is at miriam@axios.com.
  • This newsletter is 1,988 words, a 7 1/2-minute read.
1 big thing: The race to make vaccines faster

Illustration: Sarah Grillo/Axios

In the race to create a vaccine for the novel coronavirus, some researchers are testing new approaches they hope can ultimately produce vaccines in months rather than years, Eileen Drage O'Reilly and I write.

Why it matters: The global COVID-19 outbreak is a harsh reminder of the urgent need to be able to vaccinate large swaths of the population fast — in this pandemic and the next.

What's happening: The world is pinning its hopes on a vaccine for COVID-19 to save lives, return to normal, and emerge from an economic recession.

  • Experts estimate it could take at least 12–18 months for a vaccine to be widely available, with glimmers of hope for some limited availability sooner tempered by a reality that vaccines typically take multiple years to develop.

State of play: There are at least 92 vaccines under development for COVID-19 (see below).

  • 22 of those are experimental DNA- or RNA-based vaccines, which provide the most hope for speedy development.
  • "These technologies will be pushed to limits they’ve never been pushed to before, and we’ll see how they perform," Harvard Medical School's Dan Barouch says of DNA and RNA vaccines. "We’ll know a lot more about the status of these technologies at the end of COVID-19."

Background: For more than 200 years, vaccines have worked by introducing the body to either a version of the virus itself that doesn't cause disease, or an antigen that's typically a protein on the virus surface. Both prime the immune system and spur it into action should someone encounter the virus.

  • Those approaches gave the world effective vaccines for polio, measles, hepatitis B and other diseases.
  • But each time, researchers have to develop anew the biological machinery — cells and reactor conditions — needed to manufacture the vaccines.
  • This simply takes too much time during a crisis, says Johns Hopkins Center for Health Security's Amesh Adalja.

What's new: DNA and RNA vaccines are a potential avenue for speeding up vaccine development.

  • Instead of delivering the antigen, these vaccines introduce the DNA or RNA sequence that encodes the antigen, and it is produced by the body's cells. (RNA acts as an information-carrying intermediary between DNA and the protein it encodes.)
  • When a new virus emerges, the idea is an antigen from it could be quickly sequenced and the genetic code plugged into an already-approved vaccine platform with an existing tried-and-true manufacturing process. That would eliminate the long process of developing a line of cells for producing the vaccine.

But, but, but: No RNA and DNA vaccines have been approved for humans — for any virus.

  • DNA vaccines, which have been in development for two decades, sometimes struggle to cause a strong immune response to a virus.
  • RNA vaccines are a newer approach, and delivering them to the right cells can be a challenge.

Several teams are working on RNA vaccines for SARS-CoV-2, the virus that causes COVID-19, including biotech company Moderna and the NIH's Vaccine Research Center. Their RNA vaccine is in Phase I trials at three sites, testing the safety of doses and its ability to induce an immune response.

  • "If it works, it is a good technology to respond quickly. It has not been shown to work in terms of protection and to be mass produced, " Barouch says. "It doesn’t mean they can’t be; they just haven’t yet."

Meanwhile, Barouch and his collaborators at Johnson & Johnson are taking a different approach, using a non-infectious version of an adenovirus — a common cold virus — to shuttle DNA for an antigen into the body's cells.

The big picture: Testing vaccines quickly and not relying on cells to manufacture them would be a game changer for future pandemics.

  • Moving vaccine production out of cells could be one component for decentralized, local production of medicine, vaccines and diagnostics for responding to pandemics and addressing antibiotic-resistant microbes, says Northwestern University's Mike Jewett, a biochemical engineer who is developing systems for manufacturing vaccines and drugs without cells.

The bottom line: This pandemic is a testbed for the next generation of vaccine technologies.

Bonus: All the vaccines underway
Data: Milken Institute; Chart: Andrew Witherspoon/Axios

Vaccines under development around the world for the COVID-19 disease are based on different approaches, ranging from the traditional one of using an inactivated form of the virus to experimental gene-based vaccines.

Why it matters: As more vaccine platforms are cleared for safety, the process for approving new vaccines using the same platforms will be faster, says Johns Hopkins' Amesh Adalja.

The bottom line: The more successful candidates — whether traditional or modern — the better.

2. The high stakes of low scientific standards

Illustration: Aïda Amer/Axios

In the midst of this pandemic, science is suffering from low standards for some research, a new study argues.

The big picture: Science — which is slow, methodical and redundant — isn't necessarily made for the immediacy and acute public interest brought on by a health crisis, Miriam Kramer reports.

What's happening: The new paper out today in the journal Science warns that many of the clinical trials and studies first published about treatments and other issues involving the current pandemic were designed poorly or had other issues that affected their outcomes.

  • Studies that have yet to go through peer-review — like a recent, flawed study on the use of hydroxychloroquine to treat coronavirus — have found their way into news stories, leading to problematic reporting and real-time peer review through Twitter.
  • Early, flawed work has potentially increased the risk that later results may have gotten false positives and more media attention than they deserved, the new study says.

Yes, but: While the pandemic is exacerbating these problems with misinformation and lax research standards, it isn't the cause of them.

  • "Some of the problems that we're seeing right now are actually not that exceptional compared to the problems that we have under normal conditions as well, just that maybe they're a little bit more amplified and have a little more visibility," says Jonathan Kimmelman, director of the Biomedical Ethics Unit at McGill University and one of the authors of the new paper.

What's next: Many of these issues around varying standards of research and communication could be remedied through better communication among researchers and the agencies funding their work.

  • Instead of having a number of fragmented studies competing for resources and looking for effective treatments, the researchers say it would make more sense to bring the studies under one umbrella, allowing them to coordinate.
  • The authors are also calling on clinicians to resist performing their own small studies, instead opting to join up with larger trials.

Go deeper.

3. What's not helping: An infodemic

Illustration: Eniola Odetunde/ Axios

We may not have seen a global pandemic like this for the past century — but that doesn't mean we won't see another one for another 100 years.

The big picture: Experts expect infectious disease outbreaks to increase in frequency and are already noting how we can improve moving forward, Eileen writes.

Background: Last year, 15 government and business leaders took part in Event 201, a simulated pandemic exercise based on the spread of a fake coronavirus. The results were brutal.

  • By the end, it had killed 65 million people worldwide, and the global economy was wrecked.

While COVID-19 is not expected to cause that level of devastation, Johns Hopkins' Tara Sell and Eric Toner, who led Event 201, say there's already a lot to learn from this pandemic and how it differs from what they had prepared for in the exercise.

What's working: Social distancing is "flattening the curve" of infection rates, and the U.S. health care system has not yet been as overwhelmed as originally anticipated.

What's not working: There has been disparate messaging among different authorities, leading to confusion and growing distrust in the government, Sell says. This has left a void that's being filled with misinformation in what the World Health Organization has dubbed an "infodemic."

  • Event 201 also found private-public partnership was key in handling problems, and this wasn't really seen in the first three months of the COVID-19 outbreak, Toner says.

Another wild card in pandemics is how little is known about any novel pathogen.

"We've found in this outbreak that it's so hard to make decisions because there's so much uncertainty" about how it spreads and case fatality, among other things, Sell says.

What's next: There was a consensus among most leaders in the exercise on the need for a new entity connected to, but not part of, the WHO that could take charge during pandemics.

Go deeper.

4. Worthy of your time

Lawmakers say volunteers should be allowed to be infected with coronavirus (Jon Cohen — Science)

  • So-called challenge trials are a controversial strategy being put on the table to speed vaccine testing.

The people who risked death for immunity (Sarah Zhang — The Atlantic)

  • "The diseases are not perfect analogues, but in a world upended by a pandemic that has killed more than 137,000 people, immunity may once again become a dividing line," Zhang writes.

Saving coronavirus history from internet oblivion (Abby Ohlheiser and Tanya Basu — MIT Tech Review)

  • We may not want to remember this time, but history will.

The myth of the disease-spreading migrant (Lourdes Medrano — Undark)

  • "Although there have been historical instances of immigration-related disease transmission ... studies reaching back decades have repeatedly found no link between modern migration and the importation of infectious disease to host populations," Medrano writes.
5. 1 viral thing: (Corona)virus changes

Illustration: Sarah Grillo/Axios

Viruses change as they spread — the novel coronavirus included.

Why it matters: A key question for the development of diagnostic tests, vaccines and treatments is how much a virus mutates — and how efforts to fight it may have to adjust to keep up.

How it works: Viruses mutate as they replicate in host cells, producing thousands of mutations that evolution then acts upon as the virus spreads through a population.

  • RNA viruses — HIV, influenza and coronaviruses, for example — tend to mutate faster than DNA ones.
  • But unlike other RNA viruses, coronaviruses have proofreading capabilities that allow them to catch errors that arise as the virus copies itself.

Where it stands: There are no direct measurements of the raw mutation rate of SARS-CoV-2, but it is likely less than influenza and HIV viruses, says Rafael Sanjuán, who studies virus evolution at the University of Valencia in Spain.

  • As the novel coronavirus spreads around the world, researchers are tracking the changes that are occurring — a reflection of the virus' spontaneous mutations that are shaped by natural selection and other forces.
  • One example: A mutation appears to be recurring at different times and in clusters of people, suggesting it isn't random and increases the fitness of the virus, according to unpublished data that is itself evolving.
  • Yes, but: "Fitness doesn't necessarily mean a virus is more lethal," says Phoebe Lostroh, a molecular biologist at Colorado College.

The big picture: There are tradeoffs between how fast a virus replicates, how efficiently it is transmitted and how lethal it is.

  • The original SARS virus behind the outbreak in 2003 replicated low in the respiratory system, whereas SARS-CoV-2 replicates in the upper tract — meaning it can be transmitted more easily through coughing and the symptoms are less severe, letting the virus sneak under the radar in many cases.
  • The Ebola virus had a less than 50% fatality rate in the 2014 epidemic compared to 90% for all previous (and smaller) outbreaks, perhaps because mutations in the virus allowed it to be transmitted more efficiently but also made it less lethal, Sanjuán says.

Keep in mind: Technology has kept up with changes in influenza and other viruses by monitoring mutations, and there are strategies to target multiple regions of a virus with drugs and vaccines.

Bonus pic du jour

Zookeeper Lisa Fletcher interacts with Mirri the Dingo on a walk at Perth Zoo on April 23, 2020. Photo: Paul Kane/Getty Images

There are isolated cases of humans spreading COVID-19 to animals — tigers, cats and dogs — prompting zookeepers and pet owners to wear masks and socially distance from animals in an effort to protect them.

Driving the news: Two cats in New York state are the first U.S. pets to test positive for COVID-19.

"The cats, from different parts of the state, are showing only mild symptoms and are expected to be fine."
— NYT's James Gorman writes
Alison Snyder

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