[Nature] Do you know?

This article is original by Translational Medicine.
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Author: Liz Zee Guide: About a year ago, before Delta and other variants appeared, the virologists Theodora Hatziioannou and Paul Bieniasz of The Rockefeller University in New York had already started.
We have studied a key SARS-CoV-2 protein, which can evade all the antibodies that our body makes to block infection
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The goal of Theodora Hatziioannou and Paul Bieniasz is to identify the spikes (the protein used by SARS-CoV-2 to infect cells) that these neutralizing antibodies target in order to map out the key parts of our body that attack the virus
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Therefore, the researchers mixed and matched the possible related mutations found in the experiment with the virus that is spreading, and tested their "Franken Spike" against a harmless "pseudotype" virus that does not cause COVID-19.
(Franken-spikes)"
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In a study published in Nature in September this year, they reported that a spike mutant containing 20 variants is completely resistant to neutralizing antibodies produced by most infected or vaccinated testers Power-but not for everyone
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Those who have recovered from COVID-19 a few months before the vaccine injection contain antibodies that can resist mutant spikes, which are far more resistant to immune attack than any known naturally occurring mutations Body
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These human antibodies can even block other types of coronaviruses
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Hatziioannou said: "They are likely to be effective against any future variants of SARS-CoV-2
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" While the world is paying attention to the new coronavirus variants, this "super immunity" has become the biggest mystery of the pandemic.
One
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The researchers hope that by mapping the difference between the immune protection of recovery after infection and the immune protection of vaccination alone, a safer way to allow people to get a higher level of protection
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Mehul Suthar, a virologist at Emory University in Atlanta, Georgia, said: "This will affect the booster shot of the vaccine and how our immune response prepares for the next variant
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We can’t wait to figure out these issues
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"The article was published yesterday (October 14) in "Nature", titled "COVID super-immunity: one of the pandemic's great puzzles"
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Soon after the introduction of mixed immunization vaccines in various countries, researchers noticed that people who had previously been infected with COVID-19 and recovered had a different response to the vaccine than ordinary people
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Rishi Goel, an immunologist at the University of Pennsylvania in Philadelphia, who is a member of the team researching super immunity (called "mixed immunity" by most scientists), said: "We found that their antibody levels exceeded the antibody levels of two doses of vaccine
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" A preliminary study on people with mixed immunity found that compared to people who have never been infected with SARS-CoV-2 but only vaccinated, their serum (the part of the blood containing antibodies) can better prevent the virus strain from evading immunity.
For example, the Beta variant and other coronaviruses found in South Africa
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It is not clear whether this is due to high levels of neutralizing antibodies or other properties
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Recent studies have shown that at least part of the reason for mixed immunity comes from immune cells called memory B cells
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Most of the antibodies produced after infection or vaccination come from plasmablasts (plasmablasts have a short survival time in the body).
When these cells inevitably die, the antibody level will drop
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Once the plasmablasts disappear, the main source of antibodies becomes a smaller number of memory B cells triggered by infection or vaccination
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Michel Nussenzweig, an immunologist at the Rockefeller University, said some of the longer-lived cells produced higher antibody quality than plasmablasts
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This is because they evolve and mutate in the lymph nodes, which will help them bind more closely with the spike protein over time
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When people who have recovered from COVID-19 are exposed to the spikes of SARS-CoV-2 again, these cells will multiply and produce more of this highly effective antibody
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The first dose of vaccine for people who have been infected before has the same effect as the second dose of vaccine for people who have never been infected with COVID-19
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The difference between memory B cells induced by high-efficiency antibody infection and memory B cells (and the antibodies they produce) induced by vaccination may be the reason for the stronger mixed immune response
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Nussenzweig said that infection and vaccination expose the spike protein to the immune system in very different ways
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In a series of studies, the Nussenzweig team, including Hatziioannou and Bieniasz, compared the antibody response of people who recovered from infection and those who were vaccinated
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Both have the production of memory B cells, which makes antibodies more effective
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However, researchers say that people who recover from infection have higher levels of antibodies
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The team isolated hundreds of memory B cells from people at different points in time after recovery from infection and vaccination, and each cell produces a unique antibody
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Antibodies caused by natural infections continued to increase in efficacy and breadth of antibodies against variants within a year after infection, while most antibodies caused by vaccination seemed to stop changing within a few weeks after the second vaccination
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Memory B cells evolved after infection are also more likely to produce antibodies to block immune evasion variants such as Beta and Delta than memory B cells after vaccination
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Another study found that compared with vaccinations with mRNA vaccines, infections produce antibody libraries that can identify mutations more regularly by targeting different spike areas
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The researchers also found that people with mixed immunity continue to produce higher levels of antibodies for up to 7 months compared to people who have never been vaccinated
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A team led by Duane Wesemann, an immunologist at Harvard Medical School in Boston, Massachusetts, reported that antibody levels in the mixed-immune population were also more stable
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It’s not surprising that uninfected vaccinators have high antibody levels.
Researchers say that many studies on mixed immunization have not followed up on uninfected vaccinators as long as the time spent on those who have recovered from infection.
By injection or the combination of the two, their B cells may produce antibodies with greater potency and breadth
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A stable memory B cell bank may take several months to establish and mature
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There is some evidence that the antibody levels of people who have not been previously infected are catching up after receiving two vaccinations
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Ellebedy’s team collected lymph node samples from people who received the mRNA vaccine and found signs that up to 12 weeks after the second vaccination, some of the memory B cells caused by the vaccine had mutations, which allowed them to identify multiple coronaviruses.
, Including some viruses that cause the common cold
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Goel and University of Pennsylvania immunologist John Wherry, and their colleagues found that six months after vaccination, the number of memory B cells in uninfected vaccinators continued to increase and evolved a stronger ability to neutralize mutations
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After vaccination, antibody levels drop, but if these cells encounter SARS-CoV-2 again, they will begin to produce antibodies
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Goel said: "The reality is that when you encounter this antigen, there will be a high-quality memory B cell bank to protect you
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" Matthieu Mahévas, an immunologist at Sick Children, said that the third dose of the vaccine may allow uninfected people to reach a level of mixed immunity
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His team found that two months after vaccination, some memory B cells of uninfected vaccinated people could recognize the Beta and Delta variants
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Extending the vaccination interval can also simulate mixed immunization
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In 2021, in the face of a shortage of vaccine supply and a surge in cases, officials in Quebec, Canada recommended that the first and second doses of vaccine be separated by 16 weeks (later reduced to 8 weeks)
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A team led by Andrés Finzi, a virologist at the University of Montreal in Canada, found that the level of SARS-CoV-2 antibodies in people who received this recommendation was similar to people with mixed immunity
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These antibodies can neutralize a series of SARS-CoV-2 variants, as well as the SARS virus that was circulating in 2002-4
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Finzi said: "We can make uninfected people reach almost the same level as people who have previously been infected and vaccinated.
This is our gold standard
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" Scientists say that understanding the mechanism behind mixed immunity will be the key to imitating it.

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The latest research focuses on the antibody response produced by B cells, and it is likely that T cells respond differently to vaccines and infections
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Natural infection also triggers a response to viral proteins
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Some people recover for several months, the virus protein will still remain in the intestines, this persistence may help B cells to enhance the response to SARS-CoV-2
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Researchers say it is also important to determine the actual impact of mixed immunity
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A study in Qatar showed that people who received the Pfizer Biotechnology mRNA vaccine after infection were less likely to test positive for COVID-19 than people without a history of infection
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Gonzalo Bello Bentancor, a virologist at the Osvaldo Cruz Institute in Rio de Janeiro, said mixed immunization may also be responsible for the decline in the number of cases across South America
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Many South American countries experienced very high infection rates in the early stages of the pandemic, but have now vaccinated a large part of their population
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Bello Bentancor said that in terms of blocking transmission, mixed immunity may be better than vaccination alone
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With the accumulation of breakthrough infections caused by Delta variants, researchers including Nussenzweig are actively studying the immunity of people infected with the virus after being vaccinated with COVID-19
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A person's first exposure to influenza virus will bias their response to subsequent exposure and vaccination (this phenomenon is called the primitive antigen effect).
Researchers want to know whether this will happen to SARS-CoV-2
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Those who study mixed immunity emphasize that no matter what the potential benefits are, the risk of SARS-CoV-2 infection should be avoided as much as possible
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Finzi said, "We don't want everyone to be infected and then vaccinated to obtain high levels of antibodies, because this does not guarantee that everyone can recover safely
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" Reference: https:// /d41586-021-02795-x Note: This article aims to introduce the progress of medical research and cannot be used as a reference for treatment options
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If you need health guidance, please go to a regular hospital
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