What’s inside a COVID-19 vaccine, and how was it developed so fast?
Ten years of work in less than ten months — Research, Trials, and Approval
Making a vaccine is typically a very long process and can take up to 10 years from the start of research to actually distributing it to the public. The process involves various steps:
- Research
- Pre-Clinical Trials
- Phase 1 trials
- Phase 2 trails
- Phase 3 trials
- Manufacturing
- Approval by the governing body
- Distribution to public
These steps ensure that the vaccine is safe (has none or minimal side effects) and effective.
More than 72 million people are infected already, and more than 1.6 million people have died of the pandemic. A vaccine was the only hope humanity had. And scientists around the world have delivered. We now have a vaccine in less than a year since the outbreak.
Research:
One big misconception about the COVID-19 vaccine is that the research on vaccine development started after the outbreak. In the past, there have already been a few coronavirus outbreaks:
a. SARS in 2002
b. MERS in 2012
And now, we had SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in 2019–20.
Some researchers worldwide were already focused on developing a vaccine for such future coronavirus outbreaks.
At the end of 2019, the US CDC and the Chinese CDC informed of a possibility of a beta coronavirus outbreak in Wuhan, China. Soon researchers in China decoded the virus’s genome and published it online. As soon as researchers around the world got this information, they started working on developing a vaccine.
So what does a vaccine do?
Vaccines contain a weak or inactive part of a particular organism (antigen — in this case, a virus) that triggers an immune response within the body. It trains our immune system to know what a germ, such as a virus, looks like. So when the actual virus enters the body, the body recognizes the virus, knows how to fight it, thus keeping us safe.
The COVID-19 virus:
The SARS-CoV-2 virus contains three major parts:
a. Membrane Protein
b. Envelope Protein
c. Spike Protein
In figure 2, the spike proteins are the structures sticking off the side of the virus. The spike proteins are the most critical part, and they give the name of the virus — coronavirus — since they look like a crown. The virus uses its spikes to enter our cells. The spike’s 3D shape helps the virus latch on to the outside of a cell, and then it sneaks inside.
Figure 3 shows the 3 steps by which a coronavirus enters our body.
A. The 3D shaped spike proteins help the virus attach to the receptors on the outside of our cells.
B. The cell then latches on with the coronavirus.
C. Finally, the coronavirus sneaks inside and completely enters the cell.
Our body’s immune system checks these 3D spike proteins to figure out if it should attack this foreign body or not. One big problem is when the virus enters the body for the first time, the immune system does not recognize the spike proteins and is thus very slow to respond. By the time it figures out that the foreign body is a coronavirus, the virus has already multiplied multiple times, creating billions of copies of itself.
Here comes the role of a vaccine. The vaccine trains the immune system about the virus beforehand. So when there is an actual virus invasion, the immune system recognizes it instantly and is already prepared to fight it. The immune system can then kill the virus even before they enter our cells.
What’s inside the coronavirus vaccine?
A vaccine contains weak or dead viruses in many cases: Polio and Measles vaccine.
But nowadays, the vaccine contains a small piece of the virus. The COVID-19 vaccine contains just the ‘SPIKE, But for that spike to work, and to train our immune system, such that our body can recognize the actual virus, it needs to have the same 3D shape as the spike on the complete virus.
Making this spike was the challenge that researchers and scientists faced while developing the vaccine. The spike alone is a floppy floating structure and does not look like the spikes on the coronavirus.
Previous studies:
For years scientists have been studying the SARS and MERS viruses, which are very similar to the COVID-19 virus. So the scientists already knew what tiny tweaks to make to freeze the coronavirus's spikes into the perfect shape. There are two particular amino acids that, when tweaked, can stabilize the spike protein.
The spike in the coronavirus is a protein. Proteins are long folded string of individual units called amino acids. These strings of amino acids are built using code written in RNA (Ribonucleic acid) and stored in DNA (Deoxyribonucleic acid). By changing or mutating some letters of the DNA code, the amino acids in a protein can be tweaked. And this is exactly what scientists did.
Creating the spike protein:
Scientists can grow special immortal human cells outside the body. They put a modified gene for something like a spike protein into the cells, and then the cells will start creating multiple copies of these spike proteins. These cells are then run through special purification machines and isolate a pure sample of the spike protein.
The next challenge is to know if the lab-grown spike proteins look exactly like the coronavirus's original spike proteins. To overcome this problem, images are taken of the lab-grown spike using a cryo-electron microscope and compared with the coronavirus's original spikes.
Cryo-electron microscopy — Jacques Dubochet, Joachim Frank, and Richard Henderson were awarded the prize in 2017 for their work in developing cryo-electron microscopy (cryo-EM), a technique that fires beams of electrons at proteins that have been frozen in solution, to deduce the biomolecules’ structure. A beam of electrons is fired at a frozen protein solution. The emerging scattered electrons pass through a lens to create a magnified image on the detector, from which the protein structure can be worked out. Cryo-electron microscopes are so precise that they have attained the ability to locate individual atoms within a protein. Regular microscopes take pictures on the nanometer scale, but the scientists wanted to see atoms in the protein molecule, which are in the Angstrom scale. Hence a cryo-electron microscope was used.
This machine took a 3D picture of the coronavirus spike and helped design the very first coronavirus vaccines.
To take a 3D picture of the coronavirus protein using a cryo-electron microscope, a drop of protein is placed on a metal grid. It is then frozen in place using liquid ethane ( -88 degree centigrade to -182 degree centigrade). Beams of electrons are then shot at these frozen protein samples. The proteins are present in random orientations, and the electron beams leave a shadow of each of the proteins. Powerful computers then look at these 2D images, combine them to create a final 3D shape. Using the cryo-electron microscope it was seen that the lab-created spikes had the same 3D structure as the spike proteins of the coronavirus.
Trials:
These created spikes were then put in people and scientists could see if it trains the immune system of these people, and protects them from the real virus. And, it worked. The spikes protected people from COVID-19.
This is the process being used by most companies such as Pfizer-BioNtech and Moderna. The development of these vaccines is even better. The spike proteins are not created in tank cells in factories. Instead, the vaccines contain genetic instructions for making the spike, on a molecule called mRNA. When the vaccine is injected into the body, the body uses the instructions in the mRNA to make the spikes on its own. The human body itself is the factory to create the spikes.
Phase 3 trials:
Pfizer-BioNtech phase 3 trials show efficacy was consistent across age, gender, race, and ethnicity demographics; observed efficacy in adults over 65 years of age was over 94%. This vaccine has already been approved in the UK and USA.
Moderna’s COVID-19 vaccine also reached an efficacy of 94.5%.
Distribution:
While many countries have already started distributing the vaccine, it may still take a few months for everyone to receive the vaccine. Nevertheless, after 2020 being devastated by waves after waves of coronavirus, hospitals flooding with patients, and strict lockdowns across the globe, 2021 will start with new hope, thanks to science and the scientists working tirelessly to develop a virus so quickly.
Conclusion:
No vaccine in history has ever been invented this fast. It is highly effective at stopping COVID-19 and is safe. It was possible to do this so quickly, as scientists worldwide were ready. They were already studying other coronaviruses, SARS, and MERS, and they have spent years trying to understand these viruses. So when SARS-CoV-2 showed up, scientists already knew what to do and how to come up with a vaccine so quickly.