A publicly too little acknowledged achievement of scientists and the chorus of public nagging
There is currently barely a more hotly debated topic in the US, the UK, the EU, and Switzerland than the slow progress of Corona vaccinations. Journalists, politicians, managers, and all sorts of other public voices are nagging that the amount of vaccines is too small, that therefore various countries are outpacing others (as if this was a race), that the vaccination centres are not sufficiently well organized, that incidence values, R-values or other statistical quantities are subject to arbitrariness, or in general that the whole thing is not progressing fast enough. Thereby, most people lost sight of what an extraordinary scientific achievement the development of the vaccine against the SARS-CoV-2 pathogen in fact represents. It is only out of a certain ignorance that one can write, as Spiegel columnist Thomas Fricke did on March 5, 2021: „It is hard to grasp that Germany is not succeeding in vaccinating people faster in such an emergency.“ Have we already become so numb in the emotionally brackish waters of the pandemic that we can no longer show respect or even enthusiasm for the enormous scientific achievement of developing multiple COVID vaccines at once and instead prefer to wallow in the mire of permanent nagging? Has scientific progress already become such a matter of course in people’s attitudes that it can no longer even be explicitly seen and appreciated?
As for the availability of the vaccine, it was already clear a year ago, when the pandemic had just become the focus of global attention:
„The testing of the new potential vaccine is a highly complex, multi-stage process […] Such studies take months […] The biggest hurdle, however, is the production of the vaccine and its subsequent large-scale administration. Even the most optimistic pharmaceutical representative would hardly claim that the vaccine will be ready before the end of this year.“
(Lars Jaeger, What do we believe in during the Corona crisis? – In Science, March 16, 2020)
It is in fact amazing how predictable the development of the vaccine has been. One first testing subject was already vaccinated with a vaccine candidate from BioNTech on April 23, 2020. It thus took only a little more than three months from the time the gene sequence of the virus was determined (January 10, 2020) to the production of a vaccine candidate by a German company. The genetic information thus served as a blueprint for a substance (a so-called „messenger RNA“, or „mRNA“ for short, which encodes a certain specific protein of the virus) that enables the cells of a vaccinated person to produce a certain viral protein themselves. Once the body produces this protein, it is recognized by the immune system as not being the body’s own and is destroyed by appropriate antibodies and memory T cells produced by the body. This prepares the vaccinated person to fight the real virus. His or her body is thus enabled to destroy cells with this protein, just as if it had been infected with the real corona virus and was now immune to it. In the case of the SARS-CoV-2 virus, the target protein encoded in the mRNA is the special corona spike protein that sits on the surface of Sars-CoV-2 and docks with the host cells.
The American company Moderna (also using such a mRNA vaccine) was initially even faster. The first clinical vaccine sequence was completed and undergoing initial testing as early as Feb. 7, 2020, and then shipped to the U.S. National Institutes of Health (NIH) on Feb. 24, just over a month after the gene sequence announcement. The first participant in the Moderna phase 1 trial received a test vaccination on March 16, just around two months after sequence announcement. In addition to Moderna and BioNTech, another German biotech company set out to develop mRNA-based vaccines in those weeks. In June, the company, CureVac, received the green light to start a phase 1 clinical trial with its own SARS-CoV-2 vaccine candidate. It then began its second phase clinical trial in September.
By July 2020, the first results from the preclinical and clinical data from the first two phases were available for the BioNTech and Moderna vaccine candidates in Germany and the U.S. Thus, in late July the manufacturers initiated the final phase of their studies, each with more than 30,0000 volunteers, to test the efficacy and tolerability of the potential vaccines on a large scale. CureVac’s phase 3 trial began in December. So as of late summer 2020, it was clear that there was a very good chance of an effective vaccine by the end of the year. The United States, the European Union, the United Kingdom, Israel, Switzerland, and many other countries therefore began to negotiate supply contracts with the companies (some more, some less successfully).
And indeed: In November, first BioNTech and a few weeks later Moderna announced that their vaccines showed efficacy levels above 90% in each of the trials, so that they were finally emergency-approved by the authorities in both the U.S. and Europe in December „for active immunization to prevent COVID-19 disease in persons 18 years of age and older.“ In Q2 2021, CureVac, in collaboration with Novartis, will likely equally be able to move forward with the production of their own COVID-19 vaccine candidate. This will likely come with a key advantage: Unlike the vaccines from BioNTech and Moderna, it will remain stable as a ready-to-use vaccine for at least three months at a standard refrigerator temperature of +5°C and for up to 24 hours at room temperature. This makes it much more eligible for broad use. CureVac itself speaks of „positive effects on distribution, costs and material consumption.“
Meanwhile, in addition to the mRNA vaccines by BioNTech, Moderna and CureVac, also successful adenovirus-based vaccines have been developed (AstraZeneca, Johnson & Johnson, Russia’s Sputnik V, China’s CanSino Biologics). Here, the crucial gene to make the protein against the virus is inserted into a genetically modified version of a cold virus (often from monkeys), called an „adenoviral vector.“ These vaccines have an advantage over those from Moderna and BioNTech in that they are more stable than the mRNA variants: they can be stored (like CureVac’s stuff) in the refrigerator for several months, so they are considered more suitable for use in countries with weak infrastructure. In addition, they are less expensive to produce. The side effects of adenovirus-based vaccines are similar to those of the three mRNA vaccines (quite contained), as tests show, but their efficacies are somewhat lower.
These two forms are joined by vaccines that contain inactivated or attenuated viruses directly as the active ingredient (some Chinese companies rely on those), and by protein-based vaccines in which proteins of the corona virus are administered directly to stimulate the body to produce antibodies. The latter are being targeted by the U.S. company Novavax, which is currently conducting clinical trials (phase 3) in the United Kingdom and the United States. Another protein vaccine candidate is that from the pharmaceutical companies Sanofi and GlaxoSmithKline, in which much hope has long been pinned, but which disappointed in clinical trials and is now being tested in new variants.
But how come it all happened so quickly? Do we not hear time and again that the production of new vaccines takes years or even decades to succeed? This is where the enormous progress made in recent years in the long-devilled field of genetic engineering comes into play, especially in the case of mRNA vaccines. Even before the COVID-19 pandemic, it was becoming apparent that „genetic vaccines“ such as the mRNA-based agents that are now so prominent will have a significant impact on the general development of future vaccines. They were also already seen as having promising applications in cancer treatment (for example, Uğur Şahin and Özlem Türeci, the founders of BioNTech, have long been experts in identifying and characterizing new targets (antigens) for cancer tumor immunotherapy). The genetic information for combating the viruses is, so to speak, biotechnologically „programmed“ into them which is then after administration translated by the patient’s own body cells into the corresponding effective proteins. From the mRNA sequences produced are thus suitably assembled the smallest information units to combat the virus (combinations of three nucleotides for sequencing a respective amino acid). Is a comparison with the creation of a computer program too far-fetched here? Hardly, as can also be well seen from the power of the new vaccine in combating the virus’ mutations. Here, in fact, it should be possible to simply reprogram the „genetic software“ appropriately to combat the new variants. This is exactly what the mRNA vaccine manufacturers have already announced they will do.
The most time-consuming stage on the way to global effectiveness of the vaccines against the pandemic is, however, their large-scale production and subsequent equally large-scale administration. We are currently in this intermediate stage of the massive ramp-up of vaccine production with the parallel establishment of the appropriate vaccination infrastructure, which is testing our patience to such an extent that the public press seems to be in a state close to hysteria. Vaccines will soon be available in any desired quantity. On sober reflection, their development and production has so far proceeded with astonishing straightforwardness and predictability – which f we should or counter with a resounding „bravo“ to the scientists. For unlike in the professional lives of many people, the outcome and success of scientific work are anything but predetermined. What the scientists have achieved is anything but self-evident. And now, because of their success, we will finally soon be out of the woods.