Life-saving Corona vaccines: hope vs. research reality

Stefan, as a molecular biologist yourself, you have spent many years in research labs. Tell us, how is it possible to accelerate development times for a vaccine so drastically? What are the factors that can serve as accelerators?

It is a big step in the right direction that, alongside the more traditional methods for developing a vaccine, several novel lines of attack are also being explored. This more diversified approach should increase the chances of success. As of today, we estimate that there are more than 150 different Coronavirus vaccine candidates being pushed through development, at maximum speed. Under normal circumstances, it would not make sense to develop so many vaccines, all against the same virus. But the circumstances are not normal. First, since these tremendous efforts need substantial financing, governments and trusts are providing strong financial support. And second, in order to ensure that these investments are made in the most sensible way possible, collaboration is essential. Information needs to flow freely if we want to increase the chances of success for all of these projects. One example that you will often see referred to is the collaboration between the French company Sanofi and the British firm GlaxoSmithKline – which both belong to the few large producers of vaccines and, as such, are actually direct competitors. So collectively, there is an absolute desire to cooperate on a Coronavirus vaccine, from development all the way through to manufacturing. During clinical trials as well, collaboration is taking place between vaccine manufacturers. This means it should be possible to get mass production started as soon as one of the drug candidates has proven successful in trials.

“A production chain is only as fast as its slowest link.”

Everybody is pushing for speed to market. Can this have a positive outcome, or do you think that the risks are too great? After all, there’s a reason why vaccine development usually takes years, or even decades…

Because of the time pressure we’re under, vaccine candidates are moved faster to clinical trials, with time spent in pre-clinical testing kept relatively short. This will lead to a higher rate of products dropping out of clinical development compared to what we normally observe in vaccine development. In addition, it means that vaccine candidates will be tested in fewer trial participants – and that will result in fewer data available to evaluate the efficacy and safety of the drug.

In other words, in order to reach the market earlier, there is not sufficient time to optimize the vaccine. However, when development times are shortened, the risks are simply passed on to the regulatory authorities that need to give their approval for launch. For a vaccine, this process would normally take a year. But here, too, there is pressure to shorten the approval timelines. Thus, the shorter the development timelines, the higher the pressure on regulatory authorities to assume risks for the approval.

“Even worse than delayed data is disordered data.”

Leaving the US successes behind for a moment, let’s look at China. Initially, this country was accused of being very tight-fisted in the way it shared crucial data with the rest of the world. In principle, how important is it to share data immediately?

There are two aspects here that need to be balanced. On the one hand, it is essential that new findings related to SARS-CoV-2 and COVID-19 are shared as quickly as possible, in an open and transparent way. The media help make sure this is the case, as well as other channels such as scientific journals that mostly provide all relevant content free of charge. On the other hand, no matter the time pressure, the validity of the data needs to be ensured. At the onset of the pandemic, the world was more dependent on information from China, which has never enjoyed a reputation for credibility. There was also criticism that important scientific findings from other parts of the world were being published in scientific journals instead of being made directly available on the web, which caused further delay because of the peer-review process. In my view, however, if we sacrifice the extra time for reviewing and validating scientific data, crucial information would get lost in a sea of second-class speculations, observations and opinions. Sometimes you simply need to take some extra time to reach a goal even faster.

Will 12 to 18 months become the “new normal” timeline for vaccine development? Do you think that the current emergency approach will eventually lead to a disruption of traditional processes?

I don’t think so. Especially in the case of vaccines, thorough testing – particularly for safety – is of utmost importance, as these products are given to millions of healthy people.

Nonetheless, a new vaccine development technology has moved into the spotlight, the so-called “mRNA-” and “DNA-vaccines”. Contrary to traditional vaccines that use attenuated – i.e. weakened – virus, this new technology uses genetic viral material that is translated into viral protein in the body, where it is recognized by the immune system as foreign. This triggers an immune reaction that should provide the body with immunity to the real virus. This new type of vaccine can be developed and manufactured much faster compared to traditional vaccines. As great as this sounds, though, the caveat is that even though this novel approach has been in development for the past decades, it has never yet worked in humans. In other words, besides the will to win, we also need some luck that this new technology will actually prove effective, for the first time, in this emergency situation.

“Too great a speed at the beginning jeopardizes the risk/benefit assessment in the end.”

And a final question – even at the risk that your answer will already have to be revised tomorrow: Where do we currently stand? How do you judge the latest developments from “Moderna”, which has received USD 483 million from the US Biomedical Advanced Research and Development Authority (BARDA)?

Moderna’s mRNA vaccine candidate is currently among the projects that are furthest out front in the race for a Corona vaccine. On Monday, May 18th, the company published interim data from a Phase 1 clinical trial. Their vaccine candidate triggered binding antibodies in all the participants, and neutralizing antibodies were elicited in the first 8 participants to be analyzed. Neutralizing antibodies are those believed to be necessary to provide immunity. So this is exciting news and an important step in the right direction. A Phase 2 is planned with more participants to be tested, and if successful, a pivotal Phase 3 will start in July. If the Phase 3 trial is positive, the company plans to supply a few hundred million doses of the vaccine before the end of the year. As you can see, many pieces of this puzzle still need to fall into the right place – but the first, important one is already in position.