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A closer look at one of the COVID vaccine candidates

Posted on March 25, 2020March 28, 2020 by Sunil Kowlgi

A vaccine or cure for COVID is the most anxiously awaited development at the moment. There are at least 60 teams working on different approaches to a vaccine, this article is about one such vaccine.

Moderna, a US-based company developing a vaccine called mRNA-1273 for COVID, has announced they may begin a limited rollout of the vaccine in the Fall (between September to November 2020). The initial vaccine will be available only to emergency workers. A commercial rollout of the vaccine for the general public is expected to take at least 12 (March 2021) to 18 months.

Moderna is developing what is called an mRNA vaccine, which stands for Messenger Ribonucleic Acid. COVID is caused by the SARS-CoV2 virus, which our body has never seen before and thus cannot mount a defense against it. If the virus gets into our lungs, it can infect lung cells and multiply before the immune system senses something is wrong.

The SARS-CoV2 virus is spherical in shape and has what are called Spike proteins on its exterior. These are literally spike like structures and give the impression of spikes on a crown đź‘‘. The Latin word for crown is corona and therefore this virus is called a coronavirus.

This is the spike protein for #COVID2019 #SARSCoV2
You can think of it like the key that the virus uses to gain entry into our lung cells. Thanks to @McLellan_Lab for providing this model. We have more soon with up and down configurations, and hopefully some animations. #Emory pic.twitter.com/93o6rPnHJH

— EmoryVME (@EmoryVme) February 27, 2020
A 3D model of the Spike protein

A human cell is enclosed by a cell membrane. The membrane has inlets called receptors, through which things can enter a cell. There are many kinds of receptors, each receptor is like a lock and only the right shaped key can bind with it. It so happens the Spike proteins on the SARS-CoV2 can bind with the ACE2 receptor in a lung cell, letting the virus enter a lung cell, multiply and damage it in the process.

Andrew Pekosz, a virologist at Johns Hopkins University, compared viruses to particularly destructive burglars: They break into your home, eat your food, use your furniture and have 10,000 babies. “And then they leave the place trashed,” he said.

The coronavirus isn’t alive. That’s why it’s so hard to kill. – Washington Post

Check out this cool SARS-CoV-2/COVID-19 animation from @ElaraSystems that uses the spike structure we determined earlier this year with Barney Graham @NIH @KizzyPhD pic.twitter.com/r0EjgenTRo

— McLellan Lab (@McLellan_Lab) March 18, 2020
Animation showing SARS-CoV2 invading a cell

The way the mRNA vaccine is going to work is when it is injected into someone, it will make their muscle cells produce the Spike protein and then show that protein to the immune system. This way the immune system is taught to recognize the Spike protein on SARS-CoV2, and develop antibodies for it.

The vaccine is currently in Phase 1 clinical trials, which were started in Seattle. Phase 1 involves testing on 45 people. Phase 2 will involve 100s of people. Finally, there will be a large scale trial with thousands of people.

Interview with scientists working on the mRNA-1273 vaccine

Vaccine development typically takes decades, but this vaccine was ready for clinical trials 60 days from getting the genetic sequence of the virus. The previous record was for a Zika vaccine that was injected into someone 200 days into the program.

The timeline of vaccine development:

  • January: Chinese scientists release genetic sequence of SARS-CoV2
  • February: Jason McLellan’s team comes up with the atomic structure of the Spike protein
  • March: Moderna uses knowledge of the Spike protein structure to develop a vaccine and starts Phase 1 trial of the vaccine.

The scientists collaborating to develop the vaccine were able to deliver a test vaccine in record time for a couple reasons

  1. basic research on a different virus called RSV led to the development of vaccines targeting the Spike protein, and
  2. technology like Cryo Electron Microscopy (CryoEM), which was used to determine the atomic structure of the Spike protein. The invention of CryoEM was awarded the Nobel Prize in Chemistry in 2017.

It is the hard work and genius of scientists working on a vaccine and investment into research that will help get back our normal lives. Until a cure is available, we have to suppress COVID by testing, social distancing and supporting healthcare workers.


Update on March 28th, 2020

There is some research to show that targeting the Spike alone as viral antigen may have detrimental effects. Details in this twitter thread

This is a cautionary tale of how anti-Spike antibody may make COVID disease worse. In this study, the authors show that anti-Spike IgG made SARS-CoV disease worse by switching macrophage from wound-healing to proinflammatory phenotype. A thread (1/n)https://t.co/T8ipHt5tRH

— Prof. Akiko Iwasaki (@VirusesImmunity) March 28, 2020

3 thoughts on “A closer look at one of the COVID vaccine candidates”

  1. Parimala says:
    March 25, 2020 at 11:10 pm

    Thank You

    Reply
  2. Srinivasan says:
    March 26, 2020 at 4:23 am

    Good one and very informative.
    I wish all success to all scientists, Doctors and Health care workers.

    Srinivasan.K.V

    Reply
  3. K Srinivasa Rao says:
    March 26, 2020 at 4:35 am

    Thank you Sunil for a very informative article. Great contribution by the scientists and hope that the vaccine is available as early as possible for the benefit of humanity.

    Reply

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