You there -- want to make a coronavirus vaccine? Come on. I'll show you how.
After weeks of lockdown, people are starting to wonder about the long term exit plan for coronavirus. When can we get back to the workplace? When can we go out to restaurants? When can we party?
Here in New Zealand, with less than 1,000 cases to date, we are one of the few nations able to toy with the possibility of eliminating the virus pre-vaccine. It's a wild dream. One that underlines our international status as a safe haven while the world struggles with the relentless social and economical fallout of a deadly pandemic.
But what if elimination by social distancing isn't possible? Then, like 7.6 billion other people in the world, we are also waiting on that critical vaccine. A COVID-specific vaccine is the only way to restore any semblance of social normality and start repairing the battered economy.
So how can we make a coronavirus vaccine? To understand this, let's first look at what the coronavirus does to your body.
What Coronavirus Does to Your Cells
At home in the horror movie genre, the novel coronavirus bases its appearance on Pinhead by covering itself in spikes.
The virus is technically not even alive. It's just a squiggle of genetic material inside a membrane. And the spikes, of course. The spikes are key.
The spikes give the viral particle an outer glow that looks like a corona.
The newly evolved disease is one of seven types of coronaviruses that are known to infect humans:
- 4 coronaviruses take the form of common colds. These have been around for millennia and were described in Ancient Egyptian medical texts.
- 3 novel coronaviruses have recently jumped the species barrier to infect humans. These are SARS, MERS and COVID-19.
While outbreaks of SARS and MERS were comparatively well contained, nature's latest microbial antagonist has got really carried away with itself.
A large part of the problem is it's brand new. So everyone in the world is a potential host with zero immunity.
An infected person carries trillions of coronavirus particles in their airways.
When they cough, sneeze, talk or even breathe they can eject tens of thousands of droplets into your personal airspace.
Each coronavirus particle travels to the back of your nose and throat and attaches itself to your cells. It binds one of its spikes to a corresponding protein receptor in your cell membrane.
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 genetic material (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 factory workers discover the viral RNA and mistake it for your human RNA. They get to work translating the viral RNA in proteins.
In other words, it hijacks your cell's machinery to build its viral army.
Next, helpful ribosomes read the RNA strand the way you're reading this sentence, except he does it three letters at a time. He converts the code into amino acids. Here's way too much information:
The newly synthesised proteins look exactly like the components of a coronavirus. In fact, I'd go as far as saying they are the components of a coronavirus. Chemical interactions compel these 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.
The 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 f*** did that evolve?!"
I don't know. But I will point out that all life on Earth is connected by the same genetic code. And all life on Earth evolved together.
*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 covertly infiltrating your cells and using them to replicate, 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 antigen 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 a few degrees helps the lymphocytes to recognise infected cells.
But the process of producing the relevant B cells and T cells takes a few days. This latency allows the virus to make a real mess of your insides.
To combat this, your immune system has evolved a kind of 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.
Alas, coronavirus is novel. No human had ever encountered it prior to December 2019, so no-one had any COVID-19 reference material.
And although COVID-19 is similar to the SARS virus, it's sufficiently different that your immune system needs to develop a whole new specialised set of antibodies and antigen receptors.
Back to the war raging inside your infected body.
You've got a fever, you're coughing, 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. Although the global data is loose due to under-detection, currently around 20% of people infected with coronavirus need hospital treatment and 5% end up in intensive care. According to the WHO, between 1% and 3.4% of those infected will die.
That's because in some people, the virus blasts through the upper respiratory tract and reaches the lower respiratory tract, known to you and I as the lungs.
The coronavirus attacks the cells that make up the lining of the lungs. This sucks because it affects the air sacs that exchange oxygen and carbon dioxide to your bloodstream. So now it's hard to breathe.
Lung cells die en masse and 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. But 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. Inflammation ramps up even more. The whole body joins in. And your organs fail. Even with treatment (such as corticosteroids) the death rate from a cytokine storm is around 30%.
We really need to deal with this coronavirus thing. I'm so glad you volunteered to help make the new vaccine.
How to Make a Coronavirus Vaccine
Around the world, there are 40 or so teams of scientists trying to develop safe and effective coronavirus vaccines. Plus yours - and I know you very well, better perhaps than you know yourself, and personally I think you've got this sussed.
Most vaccine solutions target the spike protein, which has a complex molecular structure unique to this strain of coronavirus. The goal is to train your body up to make the complementary antibodies that target the spike protein.
One team - led by Jason McLellan at the University of Texas - has already 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 20,000 genes.
This genetic analysis tells us a great deal about the origins of the novel coronavirus. For example, COVID-19 is 89% similar to the SARS virus which jumped from bats to humans in Guangdong province in China in 2002. It's also 96% similar to a newly discovered coronavirus in bats in the Yunan province.
In fact, the intensive study of viruses in bats in recent years (spurred by the great surprise of SARS) has revealed many more betacoronaviruses which can potentially make the species jump and create more future pandemics.
But let’s deal with the issue at hand first. From the decoded COVID-19 genome, McLellan and his team inferred the specific set of genes required to build the spike protein.
The 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.
McLellan used cryo-electron microscopy to create this 3D molecular structure of the SARS-2-CoV protein spike.
Each colour shows a different protein (and its corresponding gene) which fold together into a specific functional shape. This crucial atomic map is now available to scientists everywhere to help develop vaccines.
"The molecule looks really good; it's really well behaved," said McLellan.
This is a new approach to immunity, though. Traditionally, vaccines contain dead or weakened versions of entire virus particles to train up the immune system. However, this method focuses on a small but critical appendage of the virus, stripping down the vaccine to the bare essentials.
So will it work?
That's the question which even optimistic scientists explain will take 12-18 months to fully answer. That's because it can take a few days or weeks to create a vaccine, but it takes months to check that it works and doesn't actually do more harm than good.
Without exception, all coronavirus vaccines under development will 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 99% 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.
Here's the gist of the clinical trial system:
Preclinical Trials. Typically done with animals. Tests of coronavirus vaccines on mice have generated promising results, progressing these candidates to human clinical trials.
Phase One Trials. Small groups of healthy humans show the effects of the new vaccine against a placebo. Antibody production, health outcomes and side effects are measured. Dosages start small and scale up. Some vaccines are now in this stage, such as Moderna Inc’s COVID-19 vaccine given to healthy volunteers in March 2020.
Phase Two Trials. Hundreds of healthy participants reveal the immune response across a diverse population. Researchers continue to explore different schedules of dosage, timing and method of delivery (eg, needle injection, oral dose, or the emerging microneedle array).
Phase Three Trials. Thousands of human participants get involved to test the vaccine at scale. Toxicity, efficacy and serious adverse events are monitored. Success at this stage means the FDA can review all the data and approve the vaccine for general use.
Phase Four Trials. After-market data is collected to monitor immunity long term, 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.
Here's a great 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 wins the race (that is, earns its FDA approval). Those vaccine candidates that don't finish the race will be made redundant. Let's just hope at least one horse finishes this round - otherwise the COVID saga will drag on for a long time to come.
Is Coronavirus Like The Flu?
There's a myth flying between non-scientists that coronavirus is just like the flu and therefore shouldn't be classed as a pandemic.
Here are a few stats to silence the backchat:
Our healthcare systems can't cope with this load all at once, hence the urgent construction of new hospitals to deal with the pandemic. Insufficient hospital beds, equipment and medical staff mean more people die - not just from coronavirus, but from all kinds of diseases.
The death rate from flu is 0.1% while the death rate from coronavirus is 1.8-3.4%, making COVID-19 up to 34 times deadlier.
Influenza has been around for centuries, making 40% of people immune to the flu thanks to previous infections. This herd immunity also protects the weak. Comparatively, only 0.01% of the population have so far developed an immunity to COVID-19.
The flu vaccine is given to 160 million people each year. This helps vulnerable people generate a rapid immune response. There is no coronavirus vaccine to protect those millions of sensitive individuals, so we can't think of this novel virus as "just another flu".
Flu is still a killer. I'm not belittling flu. And the flu vaccine was a great idea - without it, we'd be seeing a lot more deaths.
Likewise, a coronavirus vaccine (even if it has to be renewed annually) is the best hope we have for dealing with this disease.
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 dropping the social distancing rules.
Right now, our most optimistic hope is to begin mass distribution of a coronavirus vaccine from around September 2021.