You there—want to make a coronavirus vaccine? Come on. I'll show you how.
Here in New Zealand, we have eliminated community outbreaks of coronavirus twice. With the use of masks, contact tracing, and strict lockdowns, the Kiwi government's "go hard, go early" approach kicked COVID right up the arse. The fact that we are a remote island nation with a population of 5 million helped immensely.
But we're still acutely aware that infections are still entering at the border every day via returning residents. A single case, if ill-managed in quarantine, could bring devastation to the country. Just as it has in virtually every other country in the world.
So, like everyone else, we're still waiting on a coronavirus vaccine to bring us herd immunity. A COVID vaccine is the only way to restore normality and start repairing the haemorrhaging economy.
So how do you make a coronavirus vaccine?
- Is The Coronavirus Alive?
- How Many Coronaviruses Are There?
- What Does Coronavirus Do To Your Cells?
- How Your Immune System Reacts to Coronavirus
- What Does Coronavirus Do To Your Lungs?
- How to Make a Coronavirus Vaccine
- How Vaccines Undergo Clinical Trials
Is The Coronavirus Alive?
At home in the horror movie genre, the coronavirus bases its appearance on Pinhead by covering itself in spikes.
Spikes aside, the coronavirus is simply a squiggle of genetic material (RNA) inside a protein membrane (a capsid).
As you can see, it lacks most of the critical structures and processes that constitute life, meeting only two of the seven biological criteria:
- Order? YES - Viral RNA is made of smaller building blocks of nucleic acids. And the shell is made of smaller subunits called capsomeres.
- Reproduction? NO - While viruses do replicate, they are forced to hijack the reproductive equipment of living cells to do so.
- Growth and Development? NO - New viruses are replicated in a fully formed state, and don't use energy to increase in size or complexity.
- Energy Processing? NO - Viruses have no means to process energy. The energy required to replicate is supplied and expended by the host cell.
- Response to Environment? NO - Viruses don't actively respond to external stimuli (like light or heat) nor move of their own volition.
- Regulation? NO - While the capsid provides protection, viruses don't undertake homeostasis to maintain a constant internal environment.
- Adaptation and Evolution? YES - The outsourced replication of RNA gives rise to mutation. And viruses enter active (lytic) and dormant (lysogenic) phases which constitutes adaptation.
Overall, biologists tend to agree that the coronavirus isn't alive. But it's not quite inanimate either. It's like a whole new category unto itself.
How Many Coronaviruses Are There?
COVID-19 is a new type of coronavirus, which creates the disease SARS-CoV-2, but it's actually one of seven types of coronaviruses that are known to infect humans.
Four types of coronaviruses give us common colds. So you've already had many coronaviruses in your life. We know that they've been around for millennia because they were described in Ancient Egyptian medical texts.
Three types of coronaviruses are new, having evolved in other animals and jumped the species barrier to humans in the last two decades. These are SARS, MERS, and COVID-19.
The recent outbreaks of SARS and MERS were relatively well contained. But nature's latest microbial antagonist is really getting carried away with itself.
COVID-19 is highly contagious. In some people, it's lethal. In some, it creates flu-like symptoms. And in others, it's completely asymptomatic.
Part of the problem is that it's brand new. There is no form of immunity whatsoever. There are even documented cases of people contracting the novel coronavirus twice, thanks to the evolution of different strains.
What Does Coronavirus Do To Your Cells?
First, coronavirus needs to get inside your body. It prefers to travel as an aerosol—a suspension of fine particles in the air. Aerosols drift through the air like vapour, which is why COVID spreads more easily indoors (where there is poorer air circulation) and where people are talking, shouting, or singing.
For this reason, it's extremely wise to avoid churches, rallies, and parties during a coronavirus pandemic.
An infected person carries trillions of coronavirus particles in their airways. Every time they breathe, talk, cough, and sneeze, they eject tens of thousands of viral particles which can naturally end up in your personal airspace. COVID can even enter your body through your eyes.
Once inside, the coronavirus particles are carried to the back of your nose and throat. It attaches to your cells by binding its spike proteins to a corresponding protein receptor in your cell membranes.
This unlocks your cell, which engulfs the virus by surrounding it with its fatty membrane.
Imagine dipping a chicken nugget into a big glob of BBQ sauce until it's fully submerged. That has nothing to do with this, I just thought it would be a nice thing to imagine.
The membrane-bound virus is now inside the host cell. It injects its RNA into the cell cytoplasm.
The invasive RNA now floats freely inside your cell. Like Romeo at a Capulet masquerade party, it's operating undercover.
Soon, the cell discovers the viral RNA and mistakes it for your own human RNA. (Yes, we have RNA too. It's just a single-stranded version of DNA which is ready for expression or replication.)
The cell then gets to work translating the viral RNA into proteins. This is how coronavirus hijacks your cell's machinery to build its own viral army.
Tiny proteins called ribosomes think they're being helpful by reading the viral RNA strand the way you're reading this sentence, except they do it three letters at a time.
Then they convert the RNA code into a chain of amino acids. Here's way too much information:
The newly synthesised proteins make up all the components of a new coronavirus particle. Chemical interactions compel the parts to self assemble and—BAM!—you've cloned yourself a virus.
This viral replication occurs at scale until the cell is positively brimming with millions of newly synthesised viral particles.
The host cell has no chance. Eventually it bursts and dies, having fulfilled its ugly destiny.
The coronavirus swarm goes on to infect more cells, scaling up the rate of infection exponentially.
All of this takes place during the ~5 day incubation period, where infected people are contagious but not symptomatic.
The question on everyone's mind is: "How the flip did that evolve?"
The virus-first hypothesis says that viruses evolved from complex molecules before the first cells appeared on Earth. Which means they may have contributed to the rise of cellular life.
This idea is supported by the fact that viral genomes code for proteins that have no cellular equivalent.
*Awards issued by myself—to myself.
**The after party was amazing.
***The after party went on to win dozens of after party awards.
****These awards were also issued by me.
How Your Immune System Reacts to Coronavirus
After a few days of covert infiltration, the presence of the virus elicits an immune response. White blood cells called lymphocytes make their coordinated attack.
The main class of lymphocytes are called T cells where I'm assuming the T stands for terrific. They're covered in around 100,000 receptors which recognise the coronavirus spike protein. They bind—lock and key style—and disarm the virus.
The other major class of lymphocytes are called B cells which I'm going to go ahead and say stands for brilliant until someone corrects me. These release antibodies which circulate and stick to the virus.
To help things along, inflammatory chemicals called cytokines make their way to the brain and trigger a fever. Cranking up your body temperature helps lymphocytes to recognise infected cells.
Fun fact: every time you encounter such an infection, your immune system builds up its pathogenic library. It makes blueprints of known offenders so it can respond rapidly should they ever return. This is why you only get chicken pox once.
However, viruses like COVID mutate so fast that they are no longer recognised as the same original virus you already had.
This is why common colds always come back for more—and why we don't have vaccines for them. Mutant strains of COVID-19 (of which there are at least eight) could affect the efficacy of a coronavirus vaccine. We are likely to need annual shots to stay ahead of this thing, just as we do with influenza.
What Does Coronavirus Do To Your Lungs?
It takes your body several days to make B cells and T cells tailored to the coronavirus. And this latency gives the virus the opportunity to make a real mess of your insides.
You've got a fever, you're coughing, and you're fatigued. Life's not fair. But you're fighting trillions of viral particles right now. In a week or so you'll feel much better.
Or not. Around 20% of people infected with coronavirus need hospital treatment because it blasts through the upper respiratory tract and reaches the lower respiratory tract, known to you and I as the lungs.
Things aren't looking good. Down here, the coronavirus attacks the cells that make up the lining of the lungs. They damage the air sacs that exchange oxygen and carbon dioxide to your bloodstream. So now it's hard to breathe.
Once infected, lung cells fill up with fluid which lets in a secondary infection: bacterial pneumonia. Now your immune system is fighting two types of invasion.
Ventilators are very handy at this point, as you struggle to breathe enough oxygen to stay alive. About 5% of coronavirus patients end up on ventilators in intensive care.
And that's if they're lucky. Some countries are so overloaded that their hospitals can't even accept new coronavirus patients. People die from respiratory failure in their homes.
But let's say you did make it to a hospital. What happens next just takes the biscuit.
Remember those cytokines? They were very helpful in initiating the immune response. But now they're freaking out.
In a cytokine storm, the immune response goes into overdrive. Immune cells start attacking both infected and healthy cells.
The lungs fill with fluid, and inflammation ramps up even more. Then the whole body joins in, leading to organ failure. Even with treatment (like corticosteroids) the death rate from a cytokine storm is around 30%.
We really need to deal with this pandemic thing. I'm so glad you volunteered to make a coronavirus vaccine.
How to Make a Coronavirus Vaccine
Around the world, there are more than 100 COVID-19 vaccines in development. Plus yours—and personally I think you've got this sussed.
Most vaccine solutions introduce the spike protein to your body, but not the viral RNA.
The goal is to add the spike protein to your pathogenic library. If and when you catch coronavirus, you can then make the complementary antibodies much faster. This is the essence of immunity.
Back in March 2020, a team at the University of Texas decoded the molecular structure of the spike protein.
How? They got hold of the complete COVID-19 genome from scientists in China. It turned out to be 30,000 nucleotides making up just 15 genes. For comparison, a human has 3 billion nucleotides and 30,000 genes.
This genetic analysis told us a great deal about the origins of COVID-19. For example, it's 89% similar to the SARS virus which jumped from bats to humans in Guangdong province in China in 2002. It's also 92% similar to coronavirus in pangolins and 96% similar to a newly discovered coronavirus in bats in the Yunan province.
In fact, the study of viruses in bats (spurred by the emergence of SARS) has revealed many more betacoronaviruses which can potentially make the species jump and create new future pandemics.
But let's deal with the issue at hand first. From the decoded COVID-19 genome, the Texas team inferred the specific set of genes required to build the spike protein.
Those spike genes were replicated, then injected into mammalian cells in the lab. Being agreeable chaps, the cells started translating the genes and throwing off spike proteins for the team to study.
They then used cryo-electron microscopy to create a 3D molecular map of the SARS-2-CoV protein spike.
The colour coding reveals which genes relate to which part of the protein, which fold together into a specific functional shape. This atomic map has been invaluable in making a coronavirus vaccine.
This is a slightly new approach to immunity, though.
Traditionally, vaccines contain dead or weakened versions of entire virus particles to train up the immune system. However, this new method strips the vaccine down to the bare essentials.
How Vaccines Undergo Clinical Trials
Although you can make a coronavirus vaccine in just a few days or weeks, it takes months to check that it actually works—and doesn't do more harm than good.
All of the coronavirus vaccines in development have to go through comprehensive trials to determine dosage, formulation, side effects, adverse effects, and overall efficacy.
Imagine if we rushed out a vaccine tomorrow, which turned out to be 95% effective but had catastrophic side effects, like rendering you infertile. Or giving you brain damage. Or destroying your immune system. It would be worse than the virus itself.
Similarly, we might develop a vaccine that's completely safe, but is only 40% effective, or wears off after a few months. The short and long term efficacy must be measured, and that takes many months of waiting.
Here's how scientists run vaccines through clinical trials::
- Preclinical Trials. These are typically done with animals. Tests of coronavirus vaccines on mice generated promising results and progressed these candidates to human clinical trials.
- Phase One. Small groups of healthy humans show the effects of the new vaccine against a placebo vaccine. Antibody production, health outcomes, and side effects are measured. Dosages start small and scale up. Moderna's COVID-19 vaccine undertook this phase in March 2020.
- Phase Two. Hundreds of healthy participants reveal the immune response across a more diverse population. Researchers continue to explore different schedules of dosage, timing, and delivery method (eg, needle injection, oral dose, or the emerging microneedle array). Pfizer and BioNTech have completed a vaccine at this stage.
- Phase Three. Thousands of human participants get involved to test the vaccine at scale. Toxicity, efficacy and serious adverse events are monitored. Moderna and Pfizer are waiting for their phase three participants to contract coronavirus to test efficacy. Meanwhile, the UK's 1Day Sooner campaign is seeking participants to be vaccinated and then, somewhat controversially, actively infected with COVID to speed up the trial process. Successful completion of phase three means the FDA can review all the data and approve the vaccine for general use.
- Phase Four. Once a vaccine is approved, it enters phase four in which after-market data is collected. Scientists monitor long term immunity, adverse events, and drug interactions. This continues for years.
The eager beavers among you can volunteer for COVID-19 vaccine trials, although you have to be aware of the risks and sign a hefty legal disclaimer. Things can and do go wrong, and healthy people have died as a result of clinical trials in the past.
Here's a pretty shocking documentary about what happened when a phase one drug trial went horribly wrong in London in 2006.
The coronavirus has created such economic turmoil that governments are doing something they've never done before. They're mass producing multiple vaccine candidates before they've even been approved for general use.
By backing every horse, we're guaranteed to have a stockpile ready to go when one or more of those horses finishes the race. Those vaccine candidates that don't finish the race will be made redundant.
A vaccine isn't the only pharmaceutical player in this pandemic.
Scientists and doctors on the front line are exploring multiple coronavirus treatment options, including the use of existing FDA-approved drug combinations and the antibody-rich blood of COVID-19 survivors.
But a return to business-as-usual is a long way off. A vaccine or some other preventative drug solution is the only foreseeable route to slowing the coronavirus death count, now more one million worldwide.
The need for clinical trials means that our most optimistic hope is to begin mass distribution of a coronavirus vaccine sometime in 2021.