‘In the case of many vaccines, we don't even know how they protect us’
The rocky road of vaccine development
Cécile van Els, Professor of Vaccinology, gave her inaugural lecture on 8 June. Eight months earlier, when she was appointed professor, Van Els perhaps never suspected that her field would become so tremendously relevant and constantly be making headlines by the time she would be giving her lecture. We asked Van Els, who works for Utrecht ľϸӰ and the RIVM, about what goes on behind the scenes when a vaccine is being developed.
The coronavirus pandemic has the entire world looking expectantly at vaccine developers. Who are these developers?
‘Luckily, large-scale collaboration is taking place. Scientists and small biotech firms are cooperating with the major companies operating in the field. By doing so, they are combining the fundamental and specific knowledge of scientists with the experience major companies have amassed in connection with bringing vaccines to market. These partnerships are vital in order to prepare a solid approach. If a vaccine becomes available soon, we'll obviously be injecting it into healthy people, so we definitely do not want to make them sick.’
So what exactly is a vaccine intended to do?
‘A vaccine is a safe way to introduce a body to a pathogen. It gives the body a chance to build up an immune response.’
How long does it usually take to develop a vaccine?
‘Ten to fifteen years on average. The current record is five years, which was for the vaccine against Ebola. Right now, over a hundred vaccine developers are working on a vaccine for COVID-19, the disease caused by the novel coronavirus SARS CoV 2. This is a huge number. I think there's a good chance we'll break the record. But remember, around 90% of
all designs for potential vaccines wind up in the rubbish bin. Making a vaccine that is both safe and effective is no easy task. It can even prove impossible for some diseases. In certain cases, the interaction with the host is so complicated that developing a vaccine becomes an unbelievably complex undertaking. This doesn't give much cause for hope.’
around 90% of all designs for potential vaccines wind up in the rubbish bin
What's the predication in connection with the novel coronavirus?
‘Like any other vaccine, a vaccine for COVID-19 will need to meet the standards for safety and effectiveness. But in order to significantly shorten the development time, a number of matters are being done differently. Scientists are exchanging knowledge about the virus, vaccine technologies and testing methods at an international level, and that knowledge is informing their efforts. The stages of the vaccine development are being shortened and consolidated. What’s more, manufacturers are starting to produce vaccine candidates before it is clear whether they’ll make it to the finish line. International compensation of the risks to the private sector is making this possible. I expect that a year from now, we'll have a vaccine. This would be exceptionally fast. At that point, there's no guarantee that we'll fully understand the underlying mechanism by which the vaccine offers protection. But to be honest, there are very few vaccines for which we do know this. Our knowledge in that area is still very much in its infancy.’
Does that mean all existing vaccines were happy accidents?
‘No, I wouldn't go so far as that. Since the start of the previous century, scientists have known that the human body will make protective substances when injected with weakened pathogens. While vaccine development always makes use of evolving insights, in many cases we don't know the precise basis for the resulting protection. That's something I intend to focus on in my research. I want to unravel the chain reaction of immune responses that lead to effective and long-lasting protection.’
How do those immune responses work?
‘First to respond is the body's innate immunity, which is the immunity you are born with. This is kind of like a burglar alarm. It recognises intruders and triggers all the alarms that wake up the rest of the immune system. Next comes the most important response: the adaptive immune response, also known as acquired immunity. It specifically targets and destroys the pathogen and then ‘remembers’ it for the next time. While this immune response is very thorough in its work, it is also quite slow. The full response takes several days – and in some cases even weeks – to develop. A vaccine allows us to artificially trigger this response without time pressure, so that the recipient's immune system can go ahead and record the pathogen in its “memory”. The next time their body is infected by that particular pathogen, the vaccine recipient's adaptive immune response will immediately recognise the intruder and be able to act more quickly in response. That gives them a major advantage over the pathogen.’
This is what we all want in connection with the novel coronavirus, of course, and so the whole world is hoping vaccine developers can deliver. What is happening in that field?
‘The first thing you need is knowledge about the virus, and in particular about how it interacts with the human body and immune system. Where does such a pathogen enter the body and which components are essential for it to do so? Once you know that, you can start assembling a vaccine candidate. Next, scientists conduct studies to determine whether the product is safe and if it leads to an immune response. This is done using lab animals. That testing yields a selection of the most promising vaccine candidates.’
Are potential vaccines always tested on animals?
‘Yes, always. In order to demonstrate whether a vaccine design truly protects the recipient, scientists must conduct experiments in which the vaccinated organism is infected with the actual pathogen. When no treatment is available, as is the case with SARS-CoV-2, we obviously can't infect humans with the pathogen. Doing so could have serious consequences, which is why we still need lab animals today. Animals are also used to test the safety of the product. Only after any harmful effects have been ruled out do scientists begin to test the product on people.’
‘We might need different vaccines for specific target groups, such as elderly individuals or those with a chronic illness’
What does this involve?
‘It starts with small groups, of course: several dozen adult trial subjects and low doses of the vaccine. This is phase 1. In this phase, we are mostly testing safety. Then, in phase 2, we begin to focus more on how the vaccine affects a larger number of trial subjects: several hundred, this time. We study how often and in which dosage we must administer the vaccine. Phase 2 also includes testing on the specific target group, such as elderly individuals.’
Who is the target group for a vaccine against COVID-19?
‘Vaccines are being developed for all sorts of different age groups and target groups. People with chronic illnesses may have a different immune response than healthy individuals, and so may require a different vaccine. The same could be true for the elderly. As we age, our immune system changes. It is possible that elderly individuals will need a more powerful vaccine in order to prompt an effective immune response.’
When is a vaccine considered ready?
‘When the vaccine is both safe and effective. Scientists can demonstrate the latter in phase 3 by creating two very large groups. These will involve several thousand test subjects, ideally in a population in which the pathogen is circulating. One group is given the vaccine and the other is not. The million-dollar question then becomes: will the vaccinated group have fewer cases of illness than the non-vaccinated group? If so, the vaccine is ready.’