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Notebook Medicine

Long shots, moonshots, and your shots

(Bill Oxford/iStock)


Long shots, moonshots, and your shots

Checking in on the global effort to create a COVID-19 vaccine

In the race to defeat the coronavirus, the finish line is the mass production of a safe, effective vaccine.

Just as Jonas Salk’s vaccine helped transform polio from feared menace to historical curiosity in most countries, a good vaccine against today’s coronavirus would restore the world’s confidence, both socially (potlucks! concerts! sports!) and economically. So where does the vaccine race stand now?

The U.S. federal government’s unprecedented Operation Warp Speed project involves building factories to produce yet-unproven vaccines. That will allow the vaccines to come to market quickly if studies bear out their effectiveness. The Food and Drug Administration is speeding up the normal multiyear approval process with a “rolling review” that evaluates safety data as it comes in. (Here’s an excellent graphical summary.) The FDA has decided that, to be approved, a vaccine must make people 50 percent less likely to contract coronavirus or must reduce symptoms by 50 percent.

The nearly 150 coronavirus vaccine research projects—as of the World Health Organization’s latest count—have the same goal, but differ in their methods: Should a vaccine use an inactivated strain of the now-circulating SARS-CoV-2? Or should it use another, less dangerous virus, genetically modified to appear similar enough to the coronavirus that it will fool the person’s immune system? What if the vaccine doesn’t use a virus at all, but rather a protein the virus makes, or the messenger RNA (“mRNA”) that encodes a protein?

The World Health Organization (WHO) lists 19 vaccine candidates as having started human clinical trials as of July 6—with 130 more in pre-clinical animal studies. (Clinical research typically begins in phase 1, involving dozens of participants, and progresses to phase 3, involving thousands.)  

  • WHO lists only one vaccine candidate as having started phase 3 trials: ChAdOx1-S vaccine, a modified adenovirus vector from the University of Oxford and AstraZeneca. Sinovac’s inactivated virus vaccine is also about to start recruiting patients in Brazil for its own phase 3 trial. (The New York Times says a Wuhan-based team has also started a phase 3 trial in the United Arab Emirates.) 
  • Moderna’s mRNA vaccine has reached phase 2, with phase 3 anticipated for later this month. 
  • Oddly, the only vaccine already approved for human use is still in phase 2: China has approved CanSino’s vaccine for use in its military. That’s a risky call: A May article in Nature Biotechnology pointed out that CanSino based its vaccine on an adenovirus called Ad5—a vector to which the author estimated 45 percent of Chinese are already immune. That means the vaccine likely wouldn’t work in almost half of the population.
  • Six more candidates are in “phase 1/2” status, combining the first two stages of research by automatically proceeding with the highest vaccine dose that did not cause harmful side effects.

Thinking even further outside the box, an Australian-led team is investigating a long-known phenomenon in which the bacillus Calmette-Guérin (BCG) vaccine, used to prevent tuberculosis in the developing world, seems to boost immunity more generally. Could it reduce the chances of severe COVID-19 infection? This team had a head start, since BCG has undergone extensive study over the years. Since the only question is whether it protects against the coronavirus, the team went straight to a phase 3 trial.

If we count the repurposed BCG vaccine along with Oxford’s, Sinovac’s, and Moderna’s coronavirus-specific vaccines, the end of July will likely see four phase 3 trials progressing simultaneously—with several more planned in months to come. Even the first trials won’t finish until fall, and successful mass production doesn’t mean instantaneous availability. But accelerated approval and pre-built factories should limit delays if one or more of the candidates prove worthy.

“This is not the end. It is not even the beginning of the end,” as Churchill once said. “But it is, perhaps, the end of the beginning.”


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  • Nanamiro
    Posted: Tue, 07/07/2020 10:59 pm

    It is so bizarre that, with all the new viruses that come out every 5 years or so, we are treating this one so dramatically differently. It sounds like most people who get this virus don't even know they have it. It's already proving to be less fatal that 4 months ago. Yet we are demanding a vaccine, now.

  • PK
    Posted: Wed, 07/15/2020 10:38 am

    I am very disappointed that your coverage of possible Covid19 vaccines neglects to address the issue of how many of these vaccines are using fetal tissue lines that were obtained by elective abortions. As a Christian who is strongly pro-life, this presents serious ethical problems. I have always seen World magazine standing for the rights of the unborn, and yet in this instance you remain silent- why? 

  • jclark53
    Posted: Thu, 07/16/2020 08:36 pm

    The first thing I look for in a vaccine is fetal cells. WI-38. MRC-5.
    The next thing is whether it has live virus.

    If those are in there I really don't care how effetive it is.

  • OlderMom
    Posted: Tue, 07/21/2020 05:02 pm

    Yes, please report on which vaccines use fetal cells. 

    Also, I would like to know, what is the goal here? Are we trying to totally eradicate the virus? Is that even possible, and is this disease the same level of threat as polio? Why are there no big-picture explanations of why we should react differently about this virus?