Can immune responses alone indicate which Corona vaccine is better?

آیا پاسخ‌های ایمنی به تنهایی می‌توانند نشان دهند که کدام واکسن کرونا بهتر است؟

Is there any other way to be sure of the effectiveness of different Corona vaccines other than conducting a controlled clinical trial with newly discovered drugs that require the presence of tens of thousands of people? Many researchers believe that successful corona vaccines, which are widely used today, can be evaluated in a different way than what has been done before. In this new method, all that is needed is to measure the vaccine’s ability to elicit so-called neutralizing antibodies.

These antibodies bind to the virus and prevent it from entering the cell membrane. Several recent studies have suggested other methods of protection. According to an article published June 24, there are other types of antibodies that can be called binding antibodies. These antibodies also attach to the virus but do not block its entry. The third group of immune fighters that try to protect the body against the coronavirus are T cells.

Changes in the type of vaccines and how popular they are may soon depend on the results of such tests. Large vaccine companies are currently trying to find ways to protect against the various types of coronavirus that are occurring around the world. These companies hope that regulators will not insist on conducting clinical trials because not only are these trials time-consuming and expensive, but they are also not ethically sound because they are performed on human specimens because proven vaccines are readily available on the market.

With the help of a well-established protective correlation, the vaccine being tested can be given to a very small group of people and then tested to see if their body responds to the vaccine as needed (annual flu vaccine approvals do the same). Becomes). Thus, health authorities may change the ranking of vaccines or vote on combining their characteristics and matching them. Of course, there may be a need to develop completely new vaccines.

But finding correlations is not easy either. During the attempt to make the corona vaccine, the researchers monitored the antibody responses received and tried to link such responses to participants’ likelihood of becoming ill. In this way, not only can a big step be taken towards a better vaccine, but the information obtained will help to better understand the coronavirus.

“We always get chaotic at this stage of a dream with a strange event because different companies are reluctant to share information,” said Dr. John Moore, an immunologist at Cornell Medical Center. Many experiments to date have failed to statistically measure the correlation between inpatients and mortality. Of course, our most important task is to make a safe and appropriate vaccine for the coronavirus, but we must keep in mind that there are still other ways to evaluate vaccines and we need to get accurate results. The method of evaluating T cells is one of the methods that is not very popular due to the difficulty of measurement.

However, two studies, first published as a pre-published paper in March, underscore Moore and other scientists’ prediction of the essential role of neutralizing antibodies. To standardize the different assays used to evaluate corona vaccines, they compared the level of antibodies extracted in each vaccine with the antibodies received in people who were clinically tested. According to Moore, vaccines that elicit more stimulants provide the best protection for the body than any other condition. Thus, strong evidence of correlation is observed.

“We are very surprised by the results,” said Penny Moore, a virologist at the National Health Laboratory in South Africa who helped measure protective immune responses in various trials of the Corona vaccine. But we are a little skeptical. The question for us is what is the role of other immune responses and in what steps can they be used.

On the other hand, experiments aimed at evaluating the efficacy of RNA messenger (mRNA) vaccines have shown that the level of neutralizing antibodies is extremely low and difficult to measure. However, these vaccines, which are the result of a collaboration between Pfizer-BioNTech and Moderna, offer considerable protection. “This result shows that something beyond neutralizing antibodies is important here,” said David Montefiori, an immunologist at Duke University in the United States. In these experiments, we saw that when the second dose of the vaccine is given, neutrophils, which are responsible for healing damaged tissues and eliminating infections, increase sharply in the body to play a good protective role.

T cells, which modulate B cells, play a positive role in boosting the body’s defenses against the virus. In addition to balancing antibodies in the body, B cells help cleanse the body of infected cells.

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In a study published in February, 12 patients with mild to fatal coronary heart disease were studied. In this study, a team of researchers led by immunologist Antonio Bertoletti of Duke University reported: Patients who initially had a higher level of immunity so that T cells were activated to protect the body were less prone to coronary involvement. Because the body was able to eliminate the infection quickly.

Thus, the effective role of T cells was proved, which was supported by Moore and his colleagues. A June 11 article reviewing the effectiveness of the J&J vaccine (Johnson & Johnson) reported that 96% of people had antibodies found that could neutralize the first type of coronavirus at the onset of the epidemic. And only 19% of them had antibodies that could kill the corona beta virus.

This type of corona virus has spread in South Africa and has become extremely widespread due to negligence in communication. However, the J&J vaccine can provide significant protection against mild or even severe infection. “T cells appear to play a beneficial role in protecting the body against the virus,” says Penny Moore. An experiment in a monkey that was vaccinated and published in the journal Nature last year shows that T cells are able to provide significant protection to the body as long as the vaccine is not injected later than scheduled. .

Binding antibodies, on the other hand, could possibly be more useful than scientists think. An article published June 24 by researchers at the University of Oxford shows that 28 days after the second dose of Astraznka vaccine is injected, neutrophils are produced in the body that can protect up to 80% of the body against the virus. Further studies show that binding antibodies are less effective if they are not more effective in protecting the body.

Scientists still do not know how binding antibodies play this role. Because they do not have a direct effect on blocking infection in the body. One hypothesis is that these antibodies place the virus in the vicinity of macrophages or other cells in the class whose role is to kill viruses, or so-called invaders. Immunologist Galit Alter of the Ragon Institute under the auspices of MGH, MIT and Harvard reported in an article published in the journal Nature Medicine in March that such a function, called Phagocytosis, protects children to a high degree against the coronavirus.

Scientists suspect that it may be re-binding antibodies that are also involved in this process. These antibodies are thought to be produced by neutrophils and help the body fight off aggression.

Research by virologists Shane Crotty and Alessandro Sette of the La Jolla Institute for Immunology shows that people infected with the SARS-CoV-2 virus are more likely to develop the virus if they have T cells and antibodies that work synchronously in the body. They have failed. “The body knows how to use its best weapons to protect itself against any aggressor,” says Crotty.

An epidemic in South Africa, one of the countries that has vaccinated less than 1% of its population against the corona virus, suggests that neutrophils may sometimes not be as effective as we think. In February, the country abandoned the Astrazenka vaccine because, after a test, there were reports of a 22% failure of the vaccine.

To understand this, scientists turned to experimental tube analysis. The antibodies produced by the vaccine have very little neutralizing power against the beta type of coronavirus. Beta is the main cause of infections in the body today. On the other hand, Penny Moore’s studies on the J&J vaccine show that low levels of neutralizing antibodies should not be associated with vaccine protection. “His obsession with neutrophils may deprive him of opportunities related to the Astrazenka vaccine,” he said.

Other scientists, however, believe that it makes sense to use neutrophils as a measure of the relative potency of different vaccines. But they also acknowledge that several experiments must be performed to do this. Chinese researchers published national standards for the eradication of the SARS-CoV-2 virus in Article 23, published in June. “Ranking based on neutrophils has not been a priority for scientists,” says John Moore. But if we pass the third stage tests without a proper answer, we will have to look at neutrophils as a trump card.

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While the answers to questions about the coronavirus are still unclear, scientists must decide whether to provide the results of their data to vaccine manufacturers with all the uncertainty they have. The makers of Pfizer and Moderna are building new generations of their own vaccines that can also protect the body against the corona beta virus by producing higher levels of antibodies. The US Food and Drug Administration has said it will welcome and support the decision to build this new generation of vaccines.

“We may not be able to achieve the ultimate ideal as a result of all this research,” said Peter Gilbert, a biologist who conducts clinical trials at the Hutchinson Cancer Research Center. But the more protection we have against the virus, the more satisfied we will be. We are not looking for perfectionism here, and what matters to us is the desired level of protection of the body.

Alter, on the other hand, says in a worrying tone: “Scientists may end up relying on data obtained with neutrophils to increase the body’s defenses.” But do not worry. If we can not get the protection we need from neutrophils, we will expand our studies to eventually get the right vaccine.

We do not yet know what the relationship is between vaccines that use mRNA against the coronavirus, for example, and other vaccines. “We hope to increase our safety information in this area as well,” said Peter Marks, head of the FDA’s vaccine division.

Sette believes that despite ten different types of vaccines, scientists are open to research. Although vaccine companies provide the vaccine to the public after many tests, we must keep in mind that the information obtained after injecting the vaccine into different people also carries with it valuable information. In the next few months, various laboratories will be able to further develop vaccines by analyzing this piece of information. Today we have a valuable mountain of data available.

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