By Guest Author 24/04/2020


Becky Casale

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? In short, when will social distancing end?

In New Zealand, we are one of the few nations able to toy with the possibility of eliminating the virus pre-vaccine. It’s a wild dream. A dream that underlines our international status as a safe haven while the rest of the world struggles with the relentless social and economical implications 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 of course 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 will a coronavirus vaccine work and how can we be sure it’s safe? To understand this, let’s first take a look at our body’s natural defences against the coronavirus.

How Your Immune System Reacts to Coronavirus

When you’re infected with COVID-19, viral particles covertly infiltrate the cells in your nose and throat and use them for replication. This is called the incubation period.

After a few days, 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. 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. 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 which emerged in 2002, it’s sufficiently different that even if you had SARS, 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 underdetection, 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 me 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 a vaccine to stop this deadly impact of the coronavirus.

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. 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.

Image Source: https://science.sciencemag.org/content/367/6483/1260

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.

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 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 volunteers on 16 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 coronavirus has created such economic turmoil that pharmaceutical companies are doing something they’re never done before. They’re mass-producing multiple different coronavirus vaccines before they’ve even been approved for general use.

By backing every horse, they’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.

This article was originally published on Science Me.