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Making a vaccine no easy feat

Viruses may seem invisible. We can’t see them with our naked eyes. We can’t track their spread with our senses. But they are not invisible; just really, really small. Viruses are typically 30 to 100 nanometres in diameter.
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Viruses may seem invisible. We can’t see them with our naked eyes. We can’t track their spread with our senses. But they are not invisible; just really, really small.

Viruses are typically 30 to 100 nanometres in diameter. Much smaller than bacteria but much bigger than atoms or molecules. Indeed, a virus is little more than a bundle of molecules – a chain of some 30,000 or so RNA bases surrounded by a casing of proteins.

They all work in pretty much the same way by using the body’s biochemistry for the production of exact copies. They are that sneaky office mate who takes advantage of the copy machine when you forget to clear your code.

In the case of COVID-19, it is a coronavirus. It is encased in a capsid with spikes all over the surface. It looks like the rubber suction balls that were popular a few years ago. And the surface spikes are critical to the way the virus invades the cell.

Each spike has a protein recognition domain that targets a very specific receptor on the surface of our cells. The ACE-2 receptors are an essential component of the body’s blood pressure control mechanism.

Once the virus has latched on to an ACE-2 receptor, it is transported across the cells membrane inside a vesicle – a small sack of lipids rendering the virus soluble in the membrane and able to pass into the cytoplasm. Inside the cell, the vesicle opens allowing the virus to disperse its RNA.

Our cells produce RNA in the nucleus to be used in the cytoplasm as instructions manuals for making proteins. By releasing their own RNA, viruses hijack our protein-making machinery. In this way, they make more viruses, which are subsequently released into the body.

Our immune system normally detects these viruses. Antigen presenting cells (APCs) engulf a virus and display a small portion of its membrane proteins to activate T-helper cells. Essentially, the APCs teach the T cells what they are hunting for. And the T cells enable other immune responses.

B cells make antibodies able to block the virus from infecting other cells as well as marking the virus for destruction. Cytotoxic T cells identify and destroy virus-infected cells. Under normal conditions, our immune system keep invaders in check. B and T cells provide a long-lived memory that can protect the body against future infections.

With COVID-19, it is a novel virus our immune system doesn’t recognize. As a consequence, it spreads quickly through the body, from the lungs to kidneys and other organs, causing damage wherever it goes. By now, we are all far too familiar with the consequences of the disease.

Work on vaccines that would kick start the body’s immune system is proceeding along a number of fronts. Some are old approaches – using inactivated or weakened viruses – while others depend on modern DNA and RNA technology.

Attenuated viruses are used to treat measles and polio. Essentially, a weakened virus is created by passing it through animal or human cells multiple times until it picks up enough mutations to render it ineffective in generating disease but with enough similarities to the more virulent form so that it engages the immune system.

With modern genetic engineering, we can now short circuit the process by editing the virus’s genetic code. Or we can use chemicals, such as formaldehyde, or heat to deactivate the viral genes. But there is a fair degree of risk with this process and the resulting vaccine requires extensive testing to ensure it is safe for use.

Another alternative is to use an existing weakened vaccine virus, such as measles or adenovirus, and genetically modify its code to generate the coronavirus spike proteins. The newly approved Ebola vaccine employs this approach. With this approach, it is hoped the resulting vaccine will provoke a strong immune response and be safe for use. But there is always some risk in any case where gene insertion occurs.

A different and likely safer approach is to use human cells to generate copies of the viral protein. These would need to occur outside of the body, which would lead to issues with production. But the use of inserted DNA into human cells eliminates a number of concerns about potential adverse reactions.

The approach to a vaccine being explored by the largest number of research teams is to create the viral protein sub-units by themselves. While this would likely require the use of adjuvants to administer the vaccine, it has the advantage of providing the absolute minimum intrusion into the body. A slightly more complex version is to use empty viral shells.

All of these approaches are intended to block the proliferation of the virus once it has entered the body. They are intended to prepare our immune system by identifying the enemy before the battle. And perhaps allow us to win the war against our invisible enemy.