The timing could hardly have been better. The number of coronavirus infections had risen to a horrific high, as had the number of deaths from the virus, when the news hit global headlines: A new kind of vaccine is 90 percent effective against COVID-19.
"This data brings us a step closer to a possible solution for the current global pandemic," says Uğur Şahin, medical doctor and CEO of BioNTech, the Mainz-based biotech company that developed the vaccine together with the American pharmaceutical firm Pfizer. The two companies are currently seeking regulatory approval in the United States.
The breakthrough may not only signify the beginning of the end of the corona crisis -- it could also end up radically changing the entire approach to vaccine development. People receiving serums developed with this technology are injected with a packaged molecule containing a construction blueprint in the form of messenger RNA, or mRNA.
These molecules are absorbed by cells in the body, whereupon the mRNA prompts them to produce a specific protein. This protein, though, is "foreign" to the body and is attacked by immune cells -- thus developing immunity.
"An Historic Result"
Research into the technology has been ongoing for decades due to its potential effectiveness in fighting all kinds of diseases, including cancer. And now, in the fight against the SARS-CoV-2 virus, BioNTech and Pfizer have apparently proven that it works.
"This is a historic result, the first mRNA vaccine to show interim efficacy," says immunologist Nicholas Jackson of the Coalition for Epidemic Preparedness Innovations, an international alliance for the advancement of vaccine research. If there are no setbacks, Jackson told DER SPIEGEL, "this positive result could drive a new era of effort to apply mRNA technologies towards infectious diseases."
Norbert Pardi, a research assistant professor at the University of Pennsylvania, agrees. In comments to DER SPIEGEL, he said: "It is fantastic that the mRNA vaccine works so well." Should it prove itself, he believes, "there will very likely be more and more approved mRNA vaccines against cancer and infectious diseases in the coming years."
Researchers turned to mRNA technology for the production of vaccines in part because traditional methods are so laborious. Such vaccines are produced using weakened viruses or parts of viruses. For the production of the flu vaccine, for example, 500 million eggs are used each year to breed the influenza virus. Furthermore, this approach has proven ineffective in the battle against certain infectious diseases, such as AIDS or Dengue fever - much less in the production of a vaccine for cancer patients.
As such, it seemed all the more attractive to program cells in the body to produce the vaccine by introducing mRNA containing the appropriate construction blueprint. Researchers began experimenting with this approach more than three decades ago, injecting foreign mRNA into laboratory animals – which then implemented the blueprint and produced the foreign substance in their muscle cells.
A Cancer Vaccine?
But after this encouraging start, the field saw few advances for quite some time. The reason: mRNA proved to be extremely instable, often breaking down immediately after being injected into the body or disappearing completely. The goal became that of employing molecular tricks to pack the mRNA in such a way that it could find its way into cells without being damaged. Only in the last 10 years, says Pardi, have technical innovations and research funding transformed mRNA into a "promising therapeutic tool."
The medical expert Özlem Türeci and her husband Uğur Şahin both participated in that research. The couple was hoping to discover improved methods for treating tumors – and early on, they dreamed of being able to produce a cancer vaccine.
The basis for that vision: When cancerous tissue begins to grow, abnormal cells that look foreign to the immune system are produced. Türeci and Şahin compared healthy tissue with abnormal tissue from a specific cancer patient and were thus able to find those cells that looked foreign. They then produced mRNA containing a blueprint for precisely these foreign structures. They also improved the mRNA so that it would, in fact, reach the target cells in the body.
In one study, Türeci and Şahin administered the appropriate mRNA to 13 patients suffering from malignant melanoma, and found that each patient's immune system responded. Eight of them experienced no remission in the 12 to 23 months afterward. The treatment is unable to prevent cancer, but it could help treat it and to prevent metastasis.
The trick is that each patient receives an mDNA that is precisely tailored to the genetic profile of the cancer they are suffering from. These personalized cancer immunotherapies are still considered experimental, but the results of the initial study were so promising that Türeci, Şahin and their team were able to publish their results in July 2017 in Nature, the prominent scientific magazine. Almost two years later, a 52-year-old skin cancer patient in the U.S. received the experimental BioNTech treatment, after which he told Nature: "I was actually witnessing the cancer cells shrinking before my eyes."
Such statements should always be approached with caution, of course, but these days, dozens of companies and universities are conducting research into the technology. Clinical studies with mRNA vaccines - targeting breast cancer, lung cancer, prostate cancer and colon cancer, among others – are underway. The variety of different kinds of cancer being targeted, mRNA expert Pardi said not long ago, prove that mRNA vaccines can be instrumental in the fight against the disease.
1.3 Billion Doses
In January, though, Türeci and Şahin jumped into the race for a coronavirus vaccine essentially overnight, once they realized the gravity of the looming pandemic. Inside BioNTech, they slapped together a team that was initially 40-people strong. On the basis of the virus' genetic sequence, that team rapidly developed 20 possible vaccine candidates and began testing them on laboratory animals, narrowing down the field of potential serums. At the same time, BioNTech turned to the pharmaceuticals giant Pfizer with an offer to team up for the clinical study phase.
More than 43,500 people have thus far taken part in the Phase III study. Some of the participants received two injections of a placebo three weeks apart, with the others receiving the vaccine candidate. Neither the test subjects nor the participating doctors knew who received what. Once a total of 94 of the test subjects came down with COVID-19, the data was analyzed for the first time by independent experts. According to that analysis, the vaccine produced "more than 90 percent" protection, as the press release noted.
What about the other mRNA vaccines in direct competition with BioNTech? Franz-Werner Haas, CEO of the Tübingen-based biotech firm Curevac, told DER SPIEGEL that his company's vaccine candidate has proven to be safe at all dosage levels tested. The decisive study for approval, he said, will begin before the end of the year. And the biotech company Moderna, located in Cambridge, Massachusetts, says Norbert Pardi, could soon be able to show "similar results" to those produced by BioNTech.
Until that happens, though, all eyes are on the biotech company in Mainz, the mRNA pioneer. Despite the fact that the vaccine has to be stored and transported at minus 70 degrees Celsius, despite the fact that each dose is to cost almost $20 in the U.S., and despite its efficacy not yet being conclusively proven, the vaccine is sold out through the end of 2021. Every single one of the projected 1.3 billion doses.