The nuts and bolts

Covid-19 vaccines explained by Thomas Abraham.

Credit: James Thew/Alamy

Scientists in laboratories across the world seized upon the genome sequence of the new virus: a 30,000-character-long string of four molecules – adenine, cytosine, guanine and uracil.

Some used it to try to re-create and grow the virus in the lab; others to trace the virus’ origins and understand its place in the larger coronavirus family. And a small group of vaccine developers in Europe, North America and China used the genetic data to create prototype vaccines against Covid-19.

Within months, they had created a groaning buffet table of prototype vaccines, using a range of techniques from the traditional kind that Louis Pasteur would have been familiar with, to vaccines that are little more than tiny fragments of genetic material that can prime the immune system to ward off an infection by the SARS-CoV-2 virus.

Much focus was on cutting-edge technologies and vaccine delivery platforms that had been developed over the last decade, many of which had only been used in clinical trials, never in the general public.

Sarah Gilbert at Oxford University’s Jenner Institute had been creating a variety of prototype vaccines based on viral vector platforms, or using parts of one virus as a base to carry the proteins of another virus into the body.

Gilbert had developed a vaccine against Middle East Respiratory Syndrome (MERS), another coronavirus disease, using a chimpanzee adenovirus that had been genetically engineered to express the spike proteins of the MERS virus. When injected into the body, this vaccine virus would enter human cells and take over the cell’s machinery to make copies of the spike protein, which immune cells would recognize and build defences against.

When the new virus appeared in Wuhan, it was relatively simple to use the same technique to insert the genes for the spike proteins of this virus into the same chimpanzee adenovirus platform.

To create a vaccine, this tiny speck of genetic information is encased in a lipid bubble which allows it to penetrate a cell where it creates copies of itself

After showing promise in early clinical trials, the Anglo-Swedish pharmaceutical company AstraZeneca bought global marketing and development rights to what is now commonly referred to as the AstraZeneca vaccine.

Other vaccine developers were working on ways to simplify vaccines even further by creating so-called protein sub-unit vaccines: essentially taking the spike protein and injecting it straight into the body where it would train the immune system to create antibodies as well as other cellular defences.

Novavax, a US-based pharmaceutical company, developed a sub-unit vaccine by inducing moth cells to produce coronavirus spike proteins. These coronavirus spikes are then packaged into nanoparticles with an adjuvant to increase immune response and injected into the body.

An even more minimalist vaccine technology was used by Moderna in the US and BioNTech (which teamed up with Pfizer) in Germany.

Like most vaccine manufacturers, scientists at these two companies focused on that part of the coronavirus that was essential to infect humans: the spike the virus uses to lock onto and infiltrate cells. However, Moderna and BioNTech used not the spike itself, but the genetic code for the spike, expressed as messenger RNA, or mRNA, the form of RNA that the machinery of a cell uses to manufacture proteins.

To create a vaccine, this tiny speck of genetic information is encased in a lipid bubble which allows it to penetrate a cell where it creates copies of itself. This foreign matter replicating in the cells is detected by the immune system, which gets rid of it, and is primed for future attacks by the virus itself.

Amid this flurry of vaccine development using the latest technologies, traditional methods have not fallen by the wayside. Two Chinese companies, Sinopharm and Sinovac, had developed vaccines using one of the oldest methods available: killing the virus and injecting it into the body, to prime the immune system for future attacks.

Safety and efficacy

With this range of vaccines already in use, and more still in the pipeline, it is important to understand how safe they are and how well they protect against disease. A vaccine’s phase-three clinical trials – when it is tested on tens of thousands of people, often in different parts of the world – is where data on safety and efficacy is generated.

Both mRNA vaccines, from Moderna and Pfizer BioNtech, have produced impressive vaccine efficacy results of around 95 per cent. This figure, simply put, compares the number of vaccinated people who got Covid-19 during clinical trials to the number of unvaccinated people who got the disease. In the case of both these vaccines, being vaccinated reduced the risk of catching the disease by about 95 per cent.

Novavax reported 89-per-cent efficacy for its vaccine after its third phase of clinical trials, while AstraZeneca had an efficacy of around 70 per cent. All these vaccines comfortably exceed the minimum 50-per-cent efficacy that the World Health Organization has suggested.

As millions of doses of vaccines roll out of manufacturing plants, what impact will this have on the pandemic?

The hope is that as more and more people become immunized across the world, the virus will find less and less space to circulate and fewer and fewer people to infect, and eventually become like influenza in its behaviour: always present, but not a real threat to life, except for a few vulnerable groups like the aged, or the very young, or those who have other serious illnesses.

For this to happen, several things need to fall in place. A sizeable proportion of the world needs to be immunized. Mathematical models estimate that the number of people who need to be immunized to create so called ‘herd immunity’ ranges from 60 per cent (a best-case scenario) to over 80 per cent of the world’s population. Assuming that vaccines are distributed equitably to countries all over the world (which is unlikely) it would take two to three years for vaccine manufacturers to churn out the numbers of doses required.

While vaccine manufacturers are responsible for supply, the demand has to come from the public, supported by governments. People need to trust the vaccine, and governments need to ensure that people across the world have access to and can afford the vaccine.

As more people get vaccinated, the virus will respond to this pressure by evolving. Variants, with tiny genetic changes that are able to evade the antibodies and cell-based immune responses induced by the vaccine, will spread more easily. This is already happening with the variants that were detected in the UK, South Africa and Brazil and are now spreading globally. The creation of so many effective vaccines, at a speed that the world has not seen before, is a demonstration of what science can do. But the impact this will have on the course of the pandemic will be determined by a complex of factors: vaccine supplies, access of vaccine globally and within different countries, and the natural force of viral evolution.

Thomas Abraham teaches Journalism and Media Studies at Hong Kong University. His research work involves risk communication during infectious disease epidemics. 

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