COVID VACCINES
More than 180 different COVID-19 vaccines have been in the pipeline – and the majority of them can be placedin one of four vaccine categories. One is a classic. Two are comparatively recent. And one has never before been approved for use in humans.
Vaccines normally take up to 15 years to develop. Yet we have seen multiple vaccines for COVID-19 arrive inside a year. Here’s how they did it.
In January 2020, few people even understood the danger facing the world. But only 11 months later, scientists were ready to vaccinate against the pandemic. And after the fastest race in the history of medicine, a whole new generation of vaccines may tackle diseases beyond just COVID-19.
Physician Ugur Sahin received an email late one Friday night near the end of January 2020. At the time, very few people had realised that a new coronavirus was about to take the world’s population in its grip. But as Sahin read the scientific article to which the email directed him, he understood what was about to happen – the beginning of a war against an enemy that had not yet demonstrated its full potential. And he decided to do something about it.
At that point in time, few knew about the new virus that had emerged in the Chinese city of Wuhan and spread to the rest of China and a handful of neigbouring countries. The virus, which was later named SARS-CoV-2, had infected a total of 1347 people, of whom 41 had died of a new type of pneumonia.
In the scientific article that Sahin read, scientists from China and Hong Kong were describing how the infection had spread in a family. By studying the time period between infection and disease symptoms in each fam
ily member, the scientists concluded that the virus was spreading from human to human.
Sahin was the CEO of German drug maker BioNTech, and he realised immediately that the virus could sweep across the world, and that a vaccine would be the only efficient weapon against the nascent pandemic. Over that weekend, Sahin considered the possible paths of action, and on Monday, he summoned BioNTech’s board of directors, asking permission to immediately launch ‘Project Lightspeed’. Its aim was to develop a vaccine for COVID-19 – and to do so in record time.
Scientists find new ways
Normally, it takes 10-15 years to develop a new vaccine. The all-time record was four years. This time it was going to be achieved in under a year – and with more than 180 competitors in action.
Scientists not only had to work extremely fast, they also had to choose the most efficient method for producing their vaccine. Like all vaccines, their goal was to make the immune system produce antibodies and T cells that could combat the virus. The classic method for a vaccine is to use an inactivated or weakened version of the virus being targeted, but with this type of vaccine, scientists cannot control which parts of the virus the immune system will aim its antibodies at. Ideally, the antibodies must be aimed at a protein on the surface of the virus, one that exists only on that specific virus, so that the immune system doesn’t waste energy attacking other harmless viruses. Scientists had previously solved this problem by making a vaccine consisting of that specific protein. It’s a method that certainly works, but it is complex and time-consuming to develop. Ugur Sahin feared that such existing methods would be simply too slow. He decided that BioNTech needed to opt for a new approach.
Code trains the immune system
BioNTech already specialised in immune therapy against cancer – a type of treatment that is similar to vaccines. In both cases, the immune system is stimulated to combat the enemy. One of their preferred methods was the use of mRNA molecules. These are similar to DNA, and like DNA they can carry a genetic code that cells then use as a blueprint to produce a protein. By injecting mRNA with the code for a specific virus protein, the scientists could make the body’s own cells produce the protein − and hence train the immune system to recognise the virus.
BioNTech’s expertise with the mRNA method made Sahin believe that a COVID-19 vaccine could be developed the same way, even though other scientists had previously experimented with mRNA vaccines, and nobody had yet succeeded. However, the potential advantages were clear. An mRNA vaccine can be designed and made in the lab in less than a week, whereas it takes months to make more conventional vaccines. So by early February BioNTech had already made a series of prototypes of the vaccine that they could test on animals. Rhesus macaques and mice had a number of mRNA molecules injected into their bodies, and the scientists studied how the animals’ immune systems reacted, and whether the animals became immune to coronavirus.
BioNTech lags behind
By early April, these animal trials had been completed, and a vaccine candidate with the code name of BNT162b2 looked like a winner. The vaccine’s mRNA molecule made the immune system attack part of the spike protein on the surface of coronavirus, which the virus uses to enter body cells. One single injection of BNT162b2 made the treated animals produce sufficient quantities of both antibodies and T cells to attack SARS-CoV-2. And the vaccine protected the animals efficiently against pneumonia.
With these promising results, BioNTech teamed up with big American drug company Pfizer, and in late April, they were allowed to begin human trials in both Germany and the United States.
But in spite of such a rapid response, BioNTech and Pfizer were not leading the race to develop a COVID-19 vaccine. In the US, the companies Moderna and Inovio were already busy testing vaccines on humans. Like BioNTech, Moderna had used mRNA in its vaccine, whereas Inovio used DNA. In China, the company CanSino Biologics was testing another vaccine, this one consisting of a harmless cold virus that made body cells produce the coronavirus spike protein.
Swedish-British firm AstraZeneca had also developed a vaccine – following the same methodology as CanSino Biologics’ – and on 22 May 2020, its vaccine was the first to reach final phase 3 trials on humans. At that time, there were 19 different vaccines being tested in experiments on humans across the world, while 130 other vaccine candidates were being tested on animals. Only AstraZeneca had reached phase 3, in which the vaccine is tested on thousands of people.
In cooperation with the UK’s University of Oxford, AstraZeneca chose to carry out its trials in Brazil, where the number of new COVID-19 cases was growing rapidly day by day. Because the 40,000 test subjects were facing a high potential infection rate, the scientists had an excellent opportunities to test the vaccine’s efficiency.
Vaccines sprint towards the goal
BioNTech and Pfizer kept working. They had positive results from their phase 1 and 2 trials on humans, and in July they initiated phase 3, which involved more than 43,000 people in Germany, the USA, Brazil, Argentina, South Africa and Turkey. At the same time, they made binding agreements with authorities in the UK, the US and Japan for 250 million doses of the vaccine – although nobody yet knew if it would ultimately be approved. Australia entered into four separate agreements for the supply of vaccines once they proved effective. Meanwhile the money from the BioNTech/ Pfizer sales were quickly spent on a new vaccine factory to ensure rapid deliveries of huge quantities of vaccine once approved.
By early November, BioNTech and Pfizer had taken the lead in the vaccine race, the first to publish the preliminary results of their crucial phase 3 experiments. At that time, a total of 94 of the 43,000 test subjects had tested positive for coronavirus – 86 of them from the placebo group which had not received the vaccine, and only eight from the vaccinated group. The scientists were thereby able to conclude that the vaccine offered higher than 90% protection against infec
tion with SARS-CoV-2. The vaccine was a success. As more test results were received the result was adjusted to 95% protection.
Only one week later, Moderna reported equally good results for its mRNA vaccine candidate. And in late November, AstraZeneca finished its vaccine trials. It scored only 70% for protection, but with the advantage that it can be stored at fridge temperatures rather than the -70°C required by its competitors.
The authorities are watching
The health authorities didn’t stand idly by during the vaccine race. Whereas normally they would not begin evaluating a vaccine until after the final phase 3 trial results were available, the severity of the global situation persuaded them to follow a far more rapid strategy – though to do so without compromising on safety.
Known as a rolling review, the faster procedure involves drug makers continously submitting all preliminary results to the health authorities, which can thereby get an ongoing general idea of the vaccine’s efficiency and any side effects or similar critical results – all long before the phase 3 trials are fully completed. This allows the authorities to make a qualified decision about approval only a few weeks after receiving the final results. And that is exactly what happened to BioNTech and Pfizer with their vaccine.
The companies submitted final research results on 18 November, and on 2 December the vaccine was already approved in the UK. On 11 December, it was approved in the US, and on 21 December in the EU. Australia gave it provisional approval on 25 January 2021. At the same time, preparations for vaccination were under way. Doses had already been manufactured, the authorities had ordered and paid for them, and the infrastructure behind the distribution of the vaccines was being put into place. The EU’s first injections occurred only six days after their approval there; the first Australian vaccination took place on the morning of February 21st.
Competitors cooperate
In the wake of the Pfizer/BioNTech vaccine, the vaccines from Moderna and AstraZeneca were also approved. Many more vaccines are in the pipeline – which is a good thing. No single company could manufacture enough doses of vaccine to inoculate the whole world within a reasonable time frame. Also, the vaccines based on different principles may deliver separate strengths and weaknesses. Scientists expect that some vaccines will be more efficient for the elderly, others for young people. Some vaccines might offer very high protection that lasts for a relatively short period of time, whereas others may offer a lower level of protection over much longer periods. Scientists do not yet know which vaccines will perform best in different scenarios.
As scientists gradually answer such questions, different health authorities will be able to develop the best strategy for their struggle against coronavirus. Scientists still have much work to do, even in connection with the approved vaccines. They need to monitor who gets which vaccines when, and how many still get ill. Further research is needed on the emerging variants of SARSCoV-2, and on how long the benefits of vaccination will last.
The brains behind the Pfizer vaccine, Ugur Sahin and his team from BioNTech, are optimistic. According to Sahin, the pandemic can be effectively contained before the end of 2021 if a major part of the population is vaccinated before the third quarter of the year. Once that has happened, Sahin will aim his new mRNA weapon at other contagious diseases. Hence the race against the pandemic may eventually help cure HIV, malaria, or influenza.