Why don’t we have a COVID-19 vaccine yet? PART- I

I remember going through Instagram stories in late March, people were ranting about the pandemic, the subsequent lockdown and were venting their general frustration about the whole situation. One recurring theme was people’s anger at scientists for not having developed a vaccine for COVID-19 yet. I read people urging scientists to work harder and get on top of the situation. As a student of biotechnology who had recently taken the pharmacology course, those posts infuriated me.

On second thought, I could understand people’s frustration. It was not fun to be locked in our houses and see the world crumble around us. A lot of people are unaware of the systematic scientific process that leads to the development of a vaccine. Lack of that knowledge will lead us to believe that developing a vaccine should be easy enough and the scientists should have completed it by now at least, if not by April.

That is why I decided to write about the actual process of developing a vaccine and the steps leading up to the release of the vaccine to the general public. This post will be Part 1 of a series and will focus on pre-development and the initial research. Developing a vaccine is an arduous process that usually costs somewhere between $ 100 Million to $ 1 Billion. The cost estimate is influenced by the development cost, research expenses and the success of the drug at each phase of the clinical trial. In most cases, the entire drug development process takes somewhere between 10–12 years. So expecting scientists to have a COVID-19 vaccine ready by late March is a bit impractical. Let's see why...

The first step to develop a vaccine is to understand what you are trying to fight, in this case, COVID-19. The most challenging part of vaccine development was even harder this time as COVID-19 is a novel coronavirus, meaning, the genetic makeup of this virus has never been seen before. Researchers had to sequence the entire viral genome, which is now relatively easier due to advancement in sequencing technology and put together the entire sequence accurately. This can be especially tricky with viruses that mutate and recombine very frequently, as the viruses in the Coronaviridae family do. The entire sequenced genome was released in late January by Chinese officials.

Following this, scientists need to decipher how the virus attacks the human body, the viral proteins and the human receptors that interact for successful initiation of the infection. They need to understand the human immune response to the infection and how the virus evades it. The white blood cells (WBCs) in our body fight against any foreign particle, however, viruses evolve rapidly to dodge these defence mechanisms and establish themselves in a host body.

When developing a vaccine, scientists usually try to inhibit one of the key processes for the successful establishment of a viral infection. This means they could try to stop one of the following processes or the proteins involved. These are called drug targets.

1. Attachment of the virus to the host cell through viral protein-host receptor interaction. Think of it like a plug (viral protein) and socket (host cell receptor). The major issue here is that most of the human receptors used by viruses for attachment are usually important for other physiological functions. So just getting rid of the receptor can be fatal as it may interfere with crucial biochemical processes necessary for life. Kind of like suggesting beheading as a remedy for a headache. Works but not very effective.
2. Preventing the entry of the virus into the cell by blocking transport mechanisms. This is also a delicate process to tackle as the same transport mechanism is used to transport life-sustaining biomolecules into the cells.
3. Preventing replication of the viral genome. Viruses don’t have their own replication machinery. They use their host’s proteins to replicate their DNA and synthesize proteins. These processes can be blocked using some modified DNA particles that inhibit viral replication, however, it is very tricky and may end up interfering with human DNA replication, which is not ideal, to say the least. It can lead to cancer or severe mutations, and as much as I truly love Deadpool, I don’t think humanity is ready for that yet.
4. Preventing viral assembly and release. Once these little bastards use our own proteins against us, they take all their DNA and proteins and package it nicely into new viruses that are ultimately released into the bloodstream. A few drugs have been developed that stop these processes but their efficiency is still debated.

> The last approach is to enhance our immune response against the virus and tackle their evasion mechanisms so that our WBCs can successfully fight the infection and kill all the viruses.

Currently, many drugs that were used during the SARS and MERS outbreak are being repurposed to fight COVID-19 as they all belong to the same family of human coronaviruses. Drugs like Remdesivir and Lopinavir/Ritonavir are such potential drugs. However, the most successful COVID-19 vaccine until now, being developed by Oxford University called ChAdOx1 nCoV-19 targets T cells, a type of WBC and helps produce antibodies against the virus, thereby employing the last strategy discussed above.

On discovering a potential drug target and a molecule that acts in accordance with our hypothesis, scientists conduct many biochemical tests to characterise the drug molecule and understand the feasibility of mass production of the vaccine. Furthermore, toxicity studies need to be conducted to ensure there are no fatal side effects to the drug as that would destroy the whole purpose of drug development. If the potential drug passes all these stages, it has to be then submitted to the regulatory body of the country for clinical trials and further scrutiny. I will detail the exact process of clinical trials in the next part.

As I conclude, I want to emphasize that I have barely scratched the surface with this post. Pharmacology was a 4 credit course to be studied over an entire semester, something I can’t possibly fit into a blog post. I have skipped over quite a few important processes and barely explained in detail the exact mechanisms involved in each step. But I want to reiterate, just pre-development and research of any drug and vaccine, in itself is an excruciating process with new failures every day. The resilience and perseverance shown by scientists is nothing short of extraordinary. All of this is made more challenging by the fact that this is a virus and a disease we are still learning about. There is no solid foundation for people to base their work on and barely any time. Give our scientists some more time, show a little more patience and give them the encouragement they so desperately need.

Until next time,

Stay Safe. Wear a mask.

Shreya