The science behind the search for a COVID-19 vaccine: How do vaccines work?
Hildegund Ertle: The more different vaccines we have, the more likely we are to find one that actually works .
Humanity hopes to stop the COVID-19 pandemic with a vaccine. At least 11 vaccines are currently in the third stage of clinical trials /, Hildegund Ertl, professor at the Wistar’s Vaccine Immunotherapy Center, told the Russian service of the Voice of America how vaccines are created and how they are tested for their effectiveness and safety.
Margot Gontard: Should we expect a vaccine to appear in the near future?
Hildergund Ertl: I cannot say with absolute certainty as we do not have the results of the third phase of clinical trials yet. The results of the first and second phases of trials look promising, but they tell us nothing about the effectiveness of the vaccine..
Several vaccines are currently in Phase III clinical trials. Its goal is to recruit a large enough number of subjects to determine whether there is a significant difference in the incidence of disease between the placebo control group and the vaccinated group. The result of these tests and allows you to determine the effectiveness of the vaccine.
M.G .: How the different phases of vaccine clinical trials progress?
H.E .: There are three phases of clinical trials. The first phase is very limited trials regarding the safety of the vaccine. People are given different doses of the vaccine, starting with the smallest dose, making sure that there are no side effects.
The second phase – tests on a larger group of volunteers, usually about a hundred. At this stage, they are convinced of the safety of the vaccine and pay attention to the response of the immune system: whether antibodies and t-lymphocytes appear. During trials, vaccines against COVID-19 very often combine the first and second phases..
The third phase is key: about half of the vaccines fail at this stage. These are large-scale trials needed to compare the incidence of disease between two groups of test subjects, one receiving a placebo and one receiving a vaccine. For example, if 50 people got sick in the control group, and only 10 percent in the vaccinated group, then we can say that the vaccine is 80 percent effective. At the moment, the US Food and Drug Administration has set a goal to bring the vaccine efficacy rate to at least 50 percent. For example, if you get sick 50 people in the control group, and 25 in the vaccinated group, then you can end the test. If you get sick 50 people who received the placebo, and 26 in the vaccinated group, then you should either continue observations or declare failure.
For this phase of the trial, enough volunteers must be recruited so that there are enough cases in the control group to be able to see a statistically significant difference. For example, if you have an infection rate of about 0.1 percent in a certain month: that is, one out of a thousand people will get sick. This is not a statistically significant event. Therefore, it calculates how many people need to be recruited in order to get a statistically significant indicator in your group by a certain time. COVID-19 vaccine trials began in the summer, when the epidemic subsided in most countries. Now, with the arrival of autumn, the number of cases is growing again. So this is a floating figure.
In the process of creating a vaccine, you will inevitably face side effects. If you vaccinate a million people, it can cause unwanted reactions in some of them. And here the question is in the ratio of potential risks and benefits. For example, if five percent of those infected with coronavirus die, and one in a hundred thousand is vaccinated with side effects, but survives, then the benefits can be considered to outweigh the risks, which means you can continue to work on the vaccine..
Then you need to wait and observe which of the participants in the trials gets sick. Sometimes you have to wait for 12 months, but in the current situation we do not want to do this. Therefore, a lot of people participate in the tests..
There is another possibility that is being discussed now in the UK, but I do not like it: not to wait until people get sick, but to infect them artificially. However, the coronavirus is extremely dangerous.
Young healthy volunteers are usually recruited for such trials. As a result, you will learn how to protect young people from coronavirus, while first of all it is necessary to protect the elderly and people with chronic diseases..
M.G .: What types of vaccines are being worked on?
H.E .: Vaccines from the firms Moderna and Pfizer, which are in the third phase of clinical trials, are RNA vaccines. We have very little experience with similar vaccines..
Adenovirus vaccines, like the vaccines that Johnson Johnson and AztroZeneca are working on, have been tested to fight many infections. Adenoviral vectors are very promising platforms for vaccines, they are easier to make thermally stable – and this is a huge advantage..
RNA vaccines need to be stored at very low temperatures, minus 80 degrees Celsius. Once I got stuck in a traffic jam and, for fun, calculated how many refrigerators we need in the United States to store such vaccines: it’s just an incredible amount. And what will happen to developing countries, which are also desperate for a vaccine and do not have such refrigerators?
M.G .: How different vaccines are compared?
H.E .: All companies use different methods to test the immune response of subjects. The methods are not standardized; research is carried out in different laboratories. To check the response of the immune system to the virus, a person is injected with a vaccine, then blood is taken from him and tested for the presence of antibodies and t-lymphocytes. To do this, you can use a variety of test methods, you can use different concentrations of the virus, and also such tests can be carried out at different intervals. You can use different methods, and they all work, but they cannot be compared.
For example, in the United States, there is the HIV / AIDS Vaccine Trials Network. This is a group of people in Seattle who are working to standardize clinical trials. Most clinical trials are conducted in the United States with this network and, as a result, vaccines are comparable. This group is also involved in trials related to COVID-19..
So far, no such comparisons have been made between COVID-19 vaccines, making it very difficult to determine the best vaccine. But the more different vaccines we have, the more likely we will find one that actually works..
M.G .: What is known about the Russian vaccine “Sputnik V”?
H.E .: I am always worried when the third phase of clinical trials is not carried out, and they (the creators of “Sputnik V” – GA) began to vaccinate people without going through this phase. Also of concern is the lack of transparency and the rush to vaccinate people without sufficient large-scale safety trials. I have not even seen any reports of side effects or the mechanism of action of this vaccine
M.G .: Is the process of creating a vaccine for COVID-19 different from how vaccines are usually developed??
H.E .: I would not call him normal. For example, Johnson Johnson produces millions of doses of vaccine. No manufacturer will do this before a vaccine is licensed. So everything is being done in a hurry now. But in the end, the results will be passed on to an independent group of experts – they are not representatives of business or government, they are scientists. They will analyze the data and make a verdict on the vaccine: is it effective, is it safe?
Another question is that after the first billion people are vaccinated, we may find some side effects where they were not expected to be. But this happens with almost every vaccine..
M.G .: Who will be the first to receive the vaccine?
H.E .: Those who need it most will receive it first. These are the ones who take the first blow of the pandemic: doctors, nurses, police officers. The next will be the elderly, then people with serious chronic diseases. Perhaps later it will be given to teachers and children. People like you and me who are at medium risk will get it after people who need it more..
M.G .: Is it difficult to create a vaccine?
H.E .: It’s not very difficult to create a vaccine. With COVID-19, we are somewhat lucky, because we have encountered coronaviruses before: for example, there have been outbreaks of SARS and MERS. For example, a vaccine against the MERS virus was created in Oxford. They knew which antigen to use to create a vaccine, which greatly accelerated the process in the case of COVID-19..
I am constantly making vaccines. If I know the antigen, I can create it in a month. This means that I will have the vaccine in a test tube. But the most difficult part of the job is to test it, make sure it is safe and reproduce it in series..
On the other hand, it is really unusual how quickly everyone got involved in the process. Thanks to the state, the laboratories have money to work on the vaccine. It usually happened differently: if I made a vaccine that works well on animals, it would take 9 months before I was told, “Okay, keep working.” In another two or three years, I would have received money for the next step. And now everything is happening much faster.