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. We've used masks, contact tracing, border control, and strict lockdowns to drive a "go hard, go early" approach to kick COVID right up the arse. The fact that we are a remote island nation helped immensely.
But we're still acutely aware that infections are still entering at the border through returning residents. A single case, ill-managed in quarantine, could devastate the country. So we're also waiting on a coronavirus vaccine to create herd immunity and open the country up again. Widescale uptake of a COVID vaccine is the only way to move past this pandemic and repair the haemorrhaging economy.
So how do you make a coronavirus vaccine?
SUMMARY: COVID-19 is novel to humanity. We need to mass vaccinate at least 60-70% of the global population to break the chain of transmission and end the pandemic. Such vaccines teach the immune system how to recognise—and therefore quickly disarm—the coronavirus.
- Is The Coronavirus Alive?
- How Many Types of Coronavirus 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).
It may surprise you that viruses are not living organisms. They lack the critical structures to self-regulate and process energy, and can't even replicate without hijacking the reproductive mechanisms of living cells.
But viruses are not exactly inanimate either. They do replicate and evolve, and even have adaptive mechanisms to shift between dormant and active phases. So they belong in a whole other category unto themselves; a kind of pseudo-lifeform.
How Many Types of Coronavirus Are There?
There are seven types of coronavirus that infect humans.
Four types of human coronavirus (229E, NL63, OC43, and HKU1) cause common colds. So you've already had a number of coronavirus infections in your life. We know they've been around for millennia because their symptoms were actually described in ancient medical texts.
Three types of human coronavirus (SARS, MERS, and COVID-19) are brand new. They came about in the last two decades, by evolving in other animals and jumping the species barrier to infect humans.
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 creates the disease SARS-CoV-2 and is highly contagious. In some people, it's completely asymptomatic. In some, it creates flu-like symptoms. And in others, it's lethal.
Clearly, COVID-19 is not your basic common cold.
The problem is it's brand new to the human population, so we haven't developed any natural immunity to it yet. However, like the common cold, you can get COVID-19 twice.
How is that possible? Shouldn't our natural immunity protect us?
Not when the virus mutates. Viral evolution is many orders of magnitude faster than human evolution. Viruses can produce a new generation of offspring within hours; in humans it takes decades. That's an arms race we can't win within our lifetime, which is why we need to synthesize a coronavirus vaccine if we want to knock it out.
What Does Coronavirus Do To Your Cells?
Coronavirus prefers to travel as an aerosol: a suspension of fine particles in the air. Aerosols drift around like vapour, which is why COVID-19 spreads more easily indoors, and when people talk, shout, and sing.
This is why it's a good idea to avoid churches, rallies, and bars during a coronavirus pandemic. You can also help stop viral particles entering your body by wearing a mask.
A person with COVID-19 carries trillions of coronavirus particles in their airways. Every time they breathe, talk, cough, and sneeze, they eject tens of thousands of viral particles into the air. These particles can enter your body via your mouth, nose and even your eyes.
Once inside, the viral particles are carried to the back of your nose and throat. They attach to your cells by binding a spike protein, lock-and-key style, to a corresponding protein receptor in your cell membrane.
Each cell then engulfs the virus by surrounding it with its fatty membrane. Imagine dipping a chicken nugget into 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.
Now the membrane-bound virus is now inside the host cell. It injects its genetic material, or RNA, into the cell cytoplasm.
The invasive RNA now floats freely inside your cell cytoplasm. Like Romeo at a Capulet masquerade party, it's operating undercover.
How weird is that? The genetic material of a virus is built from the very same components as your own. Or maybe it's not so weird at all, considering both evolved on the same planet. It tells us that, very distantly, we are actually related to the viruses that are trying to kills us.
This is why, when your cell discovers the viral RNA, it mistakes it for your own human RNA. (RNA is the single-stranded version of DNA before it's expressed.)
This might be my favourite thing about cell biology, so I'm going to go into way too much detail for a moment.
Thinking they're being helpful, the ribosomes in your cells translate the viral RNA strands into proteins. They read the base pairs (G, A, C, and T/U) in sub-groups of three letters at a time called codons. Then they convert the sequence of codons to the corresponding amino acid to form a chain. Here's a ribosome doing just that:
This amino acid chain amalgamates with other chains and then folds into a very specific shape for form a functional protein. These molecules are the building blocks a new viral particle.
Chemical interactions compel the parts to self assemble and—BAM!—you've replicated a virus. No sex required.
"No sex?!" you cry, aghast.
Nope. This is essentially cloning, or asexual reproduction if you want to think of it that way. Just how bacteria do.
A Note on Viral Mutation
Occasionally, it is possible for viruses to undergo sexual reproduction, when a cell is infected with two similar strains at the same time. The newly cloned body parts mingle to produce hybrid offspring, which is one way mutant strains form.
Viruses can also mutate through coding errors in their replication. The mutants produced may be be non-functional (what we would consider disease in humans), or have superpowers like the X-Men. It's total luck of the draw.
The viral cloning occurs at scale until your cell is positively brimming with a viral army of millions. 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. And all of this takes place during the ~5 day incubation period, where infected people are contagious but not symptomatic.
Where Do Viruses Come From?
One hypothesis suggests that viruses evolved first from complex molecules, even before there were single-celled organisms. They may even have contributed to the rise of cellular life on Earth.
Another hypothesis suggests viruses arose from genetic elements that gained the ability to escape and move between cells. Read up on the Regressive, Progressive, and Virus-First hypotheses here.
*Awards issued by myself—to myself.
**The after party was amazing.
***The after party went on to win dozens of after party awards.
****These after party awards were also issued by me.
How Your Immune System Reacts to Coronavirus
After a few days of covert infiltration, the increasing volume of viral particles triggers an immune response. White blood cells called lymphocytes make their coordinated attack:
- T cells, matured in the thymus, are covered in receptors which recognise the viral spike protein. They bind to the virus, once again by lock-and-key style, and disarm it.
- B cells produce pathogen-specific antibodies which circulate and lock on to the virus. This marks them for destruction by other immune cells.
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.
But it takes your body several days to make B cells and T cells tailored to COVID-19. And this latency gives the virus the opportunity to make a real mess of your insides.
What Does Coronavirus Do To Your Lungs?
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.
And 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.
Some vaccine solutions introduce the spike protein to your body, while others use mRNA. The goal is to add COVID-19 to your pathogenic library without actually infecting you with the disease. This means when you encounter coronavirus out in the world, you can make the complementary antibodies much faster.
Every time you encounter a virus, either through natural exposure or vaccination, your immune system creates the corresponding antibodies and builds up its pathogenic library. These blueprints help it respond rapidly with T-cells and B-cells next time you encounter the disease. It's why you only get chicken pox once.
Of course, some viruses mutate so often that your old textbook editions become out of date. This is the case with influenza, and may well occur with COVID-19, too. Only time will tell.
In March 2020, a team at the University of Texas decoded the molecular structure of the spike protein.
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 that COVID-19 is an 89% match to the SARS virus which jumped from bats to humans in Guangdong province in 2002. It's also a 92% match to coronavirus in pangolins, and a 96% match to coronavirus in bats in the Yunan province.
Rather ominously, the study of viruses in bats has revealed many more types of betacoronavirus which could make the species jump to humans and create future disease outbreaks.
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 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. This new method strips the vaccine down to the bare essentials.
As of late 2020, Moderna and Pfizer have progressed mRNA vaccines to late stage clinical trials, proven to be 94.5% and 90% effective, respectively. They specifically use mRNA, where the m stands for messenger, to teach your body how to recognise the unique signature of COVID-19.
Crucially, mRNA vaccines won't infect you with COVID-19 because the genetic code is incomplete. It only offers a preview of key fragments of the viral genome, and so can't be translated into entire viral particles.
These mRNA vaccines are quite different from traditional vaccines. With the influenza vaccine, for example, scientists have to spend time creating vast batches of the weakened virus. But mRNA vaccines provide your body with the genetic instructions to perform the task of manufacturing viral proteins.
After receiving an mRNA vaccine, your muscle cells will use the partial genetic code to produce parts of the coronavirus. Peak levels occur 24-48 hours later and are sustained for a few days. A second dose after three weeks ensures maximum immunity is achieved across a population.
One downside of using mRNA vaccines is they need to be kept super cold. Pfizer says its vaccine needs to be stored at around -70°C (-94°F) lest the mRNA breaks down, and would degrade within five days in a standard freezer at 0°C (-32°F).
There are ways around this, such as modifying the mRNA and cocooning it at the molecular level. Moderna claims to have cracked the problem, offering an mRNA vaccine that can be stored in standard freezers for up to six months. This overcomes huge logistical problems and ensures fewer COVID-19 vaccines go to waste.
How Vaccines Undergo Clinical Trials
Although you can make a spiked-based or mRNA-based 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 coronavirus vaccines 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. The widescale fallout could be even 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.
- 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).
- Phase Three. Thousands of human participants get involved to test the vaccine at scale. Toxicity, efficacy and serious adverse events are monitored. 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.
A vaccine isn't the only pharmaceutical player in the coronavirus pandemic. Scientists and doctors on the frontline 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 1.3 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.