Since the vaccine was manufactured, there have been audiences asking whether the vaccine has an ADE effect. Recently, a study published in the Journal of Infectology explored the answer to this question. So whether the vaccine may cause the ADE effect, can you ask Dr. Dong? Let's do some explanations. First of all, before I talk about the ADE effect, I might want to introduce you to the concept of antibody. What is antibody? This I brought you a model to props this is a company that makes antibodies for us to do it for us. It’s a tool, so you can see that the shape of the antibody is a Y-shape. It has two arms on it, just like a person stretches out two arms. The bottom is its legs. This is the area of these two Y-shapes. This place is very important. What is this place? This is the role of its antibodies.
The antigens that bind antigens are viruses and bacteria. Their various surface protrusions are very characteristic. This place is the variable area of antibodies. It is like a transformer. It can bind a variety of different types of antigens. For example, suppose this is an antigen of a virus. What about the arm of this antibody? This multifunctional arm can hold the antigen firmly, right ? After living, it will be able to clear and eliminate the elimination that should be eliminated. This is the role of good antibodies, but this is the most anticipated vaccine. Why design a vaccine is also people hope that it can produce a lot of good antibodies. Enveloping the virus clusters and then destroying the virus in this way. But on the one hand, it is a good antibody, but in fact, there are many protrusions on the surface of the virus. It also has some antibodies that produce not good antibodies or bad antibodies. What about these bad antibodies? Not only can it not play the role of helping the antibody to eliminate it, but it may also make it possible for the antibody to catch the virus and bring it into the cell to make it easier for it to reproduce in the cell.
Antibody and its combination of the two types of good and bad antibodies that clear the virus. The antibody-dependent enhancement ADE is an abbreviation of ADE, which is Antibody-Dependent Enhancement. This antibody, the ADE effect, is related to the effect of bad antibodies. The earliest was in 1964 when Australian virologists first observed that we put the virus in a low-concentration immune serum. Why is it low-concentration? Because the concentration of the antibody in the low-concentration serum is very low when the virus is in In the environment of a very low concentration of this antibody, it found that its replication will not be inhibited but will be promoted. It promotes the virus to more easily infect other cells. It named this effect for the first time as the ADE effect and then in 1977. Scientists who studied dengue fever in the last year linked the ADE effect to the severe disease caused by dengue fever and the clinical manifestations of dengue fever.
In other words, in history, there have been reports of viruses that clearly have ADE phenomenon, dengue fever virus and SARS virus SARS virus has also reported this very serious ADE phenomenon, so let's talk about the ADE effect again here. A specific picture of what kind of a mechanism we are here is from an article published in "Nature Magazine" to explain some basic principles of this ADE effect. We can see that the picture in the upper left corner is in this Y-shape. The Y-shaped thing is an antibody, right? A good antibody is that it will draw this virus, this new coronavirus, and this virus will surround it tightly.
After it surrounds it, it is equivalent to we just encircle it. It’s the same, and finally it’s swallowed up by the phagocytes and then cleared. Doesn’t it wipe out the virus ? It’s equivalent, right? This is the ideal situation where good antibodies are produced by protective antibodies . Then we finish the new crown vaccine. What everyone measures is the titer of this good antibody. This good antibody also has an effect, which means that after it surrounds these virus clusters , the receptor of the spike protein on the surface of the virus The binding domain is masked. If it is masked, it will not bind to the ACE2 receptor on the surface of the receptor cell. This directly blocks the virus that is covered by the antibody bound by the antibody, so it cannot be very easy.
To infect this cell, so this is the protective effect of the antibody on the human body. It protects the virus from infecting it . This is a good function of this antibody. Let’s make it clear and then look at the right and draw a picture on the right. How can it be in this picture? When the site of the antibody is not the site where the good antibody binds, then it binds to the virus, but it does not bind very tightly. It just gently binds it to the site that is not the most critical. Then it turns out that this bottom end of this bottom end can pull it onto the surface of the cell. Finally, it can promote the virus to infect the cell better because it does not completely cover it.
When it pulls it in, it actually promotes the link of infection. In this case, I don’t know if I can say it like this. This is the meaning of this. Then we are saying that there is another one that is this. Of course this is before. A common phenomenon that people have observed is that this ADE effect does not happen to every virus because people often use antibody therapy to treat some viral infections, such as hepatitis B virus, such as chickenpox virus, a DNA virus. Basically, the ADE effect is not observed . It seems that the ADE effect is more like a virus-specific phenomenon . The examples just mentioned are dengue virus and SARS virus RNA viruses or The reason is that this more complex and changeable virus seems to be more prone to this ADE phenomenon. Then it is implemented in the new crown epidemic. Is there such ADE phenomenon in the new crown epidemic? We have seen a study from Duke University in the United States. It was published in In the in vitro experiment in Cell Magazine, it put the three things of virus, antibody, and cell in the same petri dish.
It found that in this case, it is targeted, that is, there is a part of the antibody. It may promote not only It will inhibit this virus from infecting cells, but it will promote these new coronaviruses to infect more and more easily infect cells. This is a basic principle shown in this picture. Of course, this mechanism has two situations. One is dependent on this ACE. Another mechanism of the portal on the cell surface of the virus that depends on the ACE2 receptor but does not depend on the invariant fragment of the antibody is to rely on the column of the antibody, so it has two different mechanisms, but this has been discovered. It is clear that this kind of in vitro experiment can promote the phenomenon that the virus infects cells. But there is a good place is that the in vivo experiment uses the same design principle to find that it does not promote the infection of the virus.
This is what it does in the in vivo experiment for everyone. In the same picture, these antibodies that can cause infection in vitro and promote infection in the body do not promote the infection of the new coronavirus. So this thing is to give you a reminder, but you don't need to worry too much, but at least this is the first one. This is for everyone to clarify The reminder that the factors that may increase the infection do exist in the case of the new coronavirus. It is based on this experiment. Before the emergence of Omicron , when the Delta variant was popular, it came from the French National Institute of Health and Medicine. In August this year, the scientists published a study in the Journal of Infection. They followed the previous study and went on to do it because the study just used the old virus and the old virus was used, and it was discovered that there was antibody dependence.
They replaced the Delta mutant virus with the Delta mutant virus and saw if there was this phenomenon, and found that the Delta mutant virus also has this phenomenon, and they have made the mechanism more in- depth to what level it is he Take the fragment of the antibody that has been observed in the previous study that clearly can cause the enhancement of antibody dependence to make a molecular simulation with this Delta variant virus and make a three-dimensional one-molecule simulation picture. We can see on the left. On the left of this picture, see the part of the cell membrane in the picture.
The red part is this is a component of the cell membrane, and then on the far right is a large inverted triangle and a cone-shaped structure. This is a three-dimensional structure of the spike protein and then the yellow area. It’s the N- terminal binding domain. There are some fragments of the N-terminal binding domain. This is some fragments that produce bad antibodies. Look at this. The bad antibody is marked with the green one. The bad antibody binds to a certain part of the spike protein and at the same time it also binds to a part of the cell membrane. Then how does it promote this virus to better Delta virus It’s easier to infect the cells of the human body. People zoomed in on the sequence of the bad antibody and finally found that the bad antibody has two circular structures. Just the right picture. The right picture has two circles. It’s like this boat, when it’s going to dock, the cable that it will throw out has to be tied to the anchor, right ? These two ring structures are tied to the yellow area of the spike protein on one side, which is N This area on the other end is tied to the part where the spike protein binds to the cell membrane surface.
This is the red area. So for another analogy, it’s like a person holding the bad antibody with two hands and one hand. It pulls this part of the spike protein and the other hand pulls this part of the cell membrane, which is equivalent to a strong bond, which significantly strengthens the adhesion between the spike protein and the cell surface, so it further promotes The conformational change of the receptor binding domain of the spike protein is the next step of the membrane fusion process for the virus to infect cells, which promotes the process of membrane fusion, laying a very fast membrane fusion and laying a foundation. With this step , the next step is the virus infects the cells. This process occurs. So the author of this study proposed a concern, which means that in the case of the old virus, the effect of good antibodies and neutralizing antibodies is obviously higher than this. The role of bad antibodies, so when the vaccine is vaccinated, there is still a relatively good protection against the old virus infection, that is, the upper part of the balance, when the neutralizing antibody is obviously higher than the ADE.
But if in the case of the Delta variant virus, the effect of the bad antibody is because the affinity between it and the Delta variant virus is more obvious and stronger than the old virus, so it is easier to make the Delta variant. Viruses are more likely to bind to the surface of this receptor and invade cells more easily, so this is why people raise a concern that the increased dependence of this antibody may be disadvantageous in dealing with this new variant infection . The effect is not good for people to clear the infection of this variant virus, so it is right. So this means that if the bad antibody increases, it is possible to assume that someone was infected with the old virus before and healed and later it was infected with the Delta variant.
If it is bad If the antibody plays a role in it, it is likely that the Delta variant virus infection behind it may be more likely to worsen into a severe infection. If this happens, be vigilant. The possibility of the ADE effect is also mentioned. This study also suggests that this may be a potential risk of mass vaccination. So how can a vaccine be designed to avoid this ADE effect, so it is necessary to use some The vaccine that lacks the production of bad antibodies is to knock out the fragment of the bad antibody, and then try to avoid the production of this bad antibody.
As you mentioned earlier , many people infected with the Omicron variant are the first to be infected. Is it possible that people with three doses of the vaccine are due to the ADE effect? This possibility really means that it cannot be completely eliminated because we have just mentioned that this includes the ADE effect. A new report in the last November that reported the death of this Covid infection 28 days after the diagnosis , the proportion of fully vaccinated cases is higher than the proportion of non-vaccinated cases. Of course, this interpretation of this data we should also pay attention to because this death is not The death of this Covid infection is just a death 28 days after his diagnosis, so this bad antibody may indeed aggravate the condition, but that is to say, will Omicron also have this hidden danger, then we also hope that the scientists Let’s do a study on the bad antibody of Omicron as soon as possible to see if the affinity has also increased significantly. This is very important. In addition, as more and more data on the administration of the vaccine are released, we find that the vaccine is not getting more and more hits.
The more you are, the better . The methodology of modern medicine is to focus on this part of the virus, find the spike protein, and then design a vaccine. Hope this vaccine can help solve all the problems of the virus. But if you pay too much attention to it, you often lose the whole because the virus is also It's not just protein, right? It's a complete life phenomenon, but there are also many intangible ingredients that people can't see, but they are objectively real. So I really feel that this epidemic has brought a huge impact to people. Hope that people can open their minds and jump out of some thinking boxes to think deeply and rationally about the real reason behind this wave of variants.
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