Why the COVID-19 vaccine can provide stronger immunity than natural infections

Eighteen months after the first officially reported SARS-CoV-2 case appeared in Wuhan, in the early stages of the pandemic, including what immunity is generated from natural infections and how long it lasts. Can start investigating questions that could not be answered. One is protected from reinfection and does vaccination produce better immunity than natural exposure to the virus?

A Recent preprint researchThe Oxford University scientists provide the most thorough explanation of the immune response of COVID-19 patients who have recovered to date. Nearly 80 healthcare professionals were closely tracked for six months after infection, and researchers used a new machine learning approach to analyze immune biomarkers.

“After COVID-19, individuals show very different immune responses from each other, and some people in both the symptomatic and asymptomatic groups show evidence of immunological memory 6 months or earlier after infection. I found that it wasn’t. ” The author of the study explains Christina Dordo.

In general, this study found a correlation between disease severity and a sustained immune response. Over 90% of asymptomatic cases did not show a measurable immune response after 6 months. A quarter of symptomatic cases lacked immunity that lasted for 6 months after infection.

But a little more worrisome was the discovery that few serum samples from infected subjects showed an antibody response to new mutants of the virus. Dold seems to suggest that this may suggest that people infected with the original SARS-CoV-2 strain in 2020 may have little protection from some of the new variants that have begun to circulate. Is called.

“Our concern is that these people may be at risk of being infected again with COVID-19, especially if new variants are in circulation,” says Dold. “This means that it is very important for all of us to get the COVID vaccine.”

But why is the immunity produced by the vaccine different from natural infections?

“Honestly, we don’t know.” Sabra Crane says, Johns Hopkins Bloomberg Immunology Specialist at the Graduate School of Public Health. “The immune system of infected people is trained to target all these different parts of the virus, called antigens. You would think it provides the strongest immunity, but it is not.”

Innate immunity is unpredictable

One of the biggest problems with innate immunity that arises from SARS-CoV-2 infection is how variable and unpredictable it is. A Impressive research Announced earlier this year, they found a surprising range of innate immune responses in recovered COVID-19 patients. Comfortably, the paper saw an immune response from a natural infection that lasted at least eight months, but also showed that some recovered patients showed 100-fold higher immune levels than others. I am.

“Therefore, if you’re playing a basketball game and one gets 1 point and the other gets 100 points, their equivalent performance isn’t considered,” said corresponding author Shane. Crotti explains. USA Today.. “And that’s how we also think about immune responses. They’re there, but not everyone is equal.”

A More recent research, Not yet peer-reviewed and published, but compared long-term antibody responses between naturally infected subjects and subjects immunized with the mRNA vaccine. After two doses of vaccination, antibody levels were found to be up to 10-fold higher than plasma after spontaneous infection.

RBD clues

A strong new study published in the journal provides clues as to why vaccine-induced immunity may be stronger than natural infections. Scientific translation medicine.. This study, by a team at the Fred Hutchinson Cancer Research Center, focused on a specific part of the SARS-CoV-2 virus called the receptor-binding domain (RBD).

Perhaps everyone has heard of the infamous spike protein of SARS-CoV-2. It is this new protein that allows the virus to infect humans by attaching to a receptor called ACE2 that is present in some of our cells.

It is the RBD fragment that acts as a kind of interface between the viral spike protein and the ACE2 receptor in human cells. These are like anchors that help the virus fuse with the ACE2 receptor and eventually infect human cells.

A new study analyzed thousands of possible RBD variants. The goal was to compare how much the vaccine-induced antibody targeted RBD compared to the antibody produced by natural infection.

“By scrutinizing the results, researchers have revealed an important difference in acquired immunity between those who have been vaccinated and those who have previously been infected with SARS-CoV-2,” said the National Institutes of Health. Is written by Francis Collins, the director of. , In the statement Explain why vaccination is important even for people who have been infected before.

“Specifically, antibodies induced by the mRNA vaccine focused on RBD compared to antibodies induced by infections, which often target other parts of the peplomer. In particular, vaccine-induced antibodies targeted a wider range of locations on RBD than those induced by spontaneous infection. “

The results of this new study provide insight into how vaccination is protected against the new SARS-CoV-2 mutant. However, it is not yet clear why vaccination acts so specifically on RBD.

Klein argues that the reason behind strong vaccine immunity may be that the vaccine may be a way to present the immune system with only large amounts of peplomer. This extreme focus on only a portion of the virus can increase the ability to develop effective antibodies.

“It’s like a big red button on the surface of a virus. It really sticks out there, and that’s what our immune system sees most easily.” Klein says.. “By focusing on this one big antigen, we are blindfolding our immune system so that we can only see that one virus.”

Another hypothesis raised by the research team behind the new RBD study is that vaccines, especially mRNA vaccines, present antigens to the immune system in a very different way than natural infections. This includes the fact that vaccines expose different parts of the body to antigens, which do not occur with natural viral infections.

“… Spontaneous infections only expose the body to the virus in the respiratory tract (unless the disease is very severe), but the vaccine is delivered to the muscles. In muscles, the immune system can see it and react actively. It’s even more sexual, “explains Collins.

Hybrid immunity

More and more studies have found that a single vaccination of a previously infected subject can provoke a greater immune response than a double vaccination of an uninfected person.Very recently UCLA-led research Previously infected COVID-19 subjects confirmed that they required only one mRNA vaccination to generate a strong antibody response.

“Our data suggest that people who have previously been infected with COVID-19 respond significantly after the first mRNA vaccination, with little or no effect from the second vaccination. ” Ottoyan says, Senior author of the study. “It is worth considering changing public health policies to take this into account in order to maximize vaccine use and avoid unnecessary side effects.”

Crotty, a vaccine scientist at the La Jolla Institute for Immunology, explains how the combination of innate and vaccine-producing immunity can synergize to create a type of “heterosis.” This means that people previously infected with SARS-CoV-2 are better protected from new variants after vaccination than relying solely on protection from natural infections.

“… Neutralizing antibody against B.1.351[the beta variant] After vaccination of individuals previously infected with non-B.1.351 SARS-CoV-2, 100 times more than infection alone and 25 times more than vaccination alone, even though neither vaccine nor infection was accompanied by B.1.351 spikes. was. Write to Crotty Recent outlook articles..

rapidly Rise of delta variantsThese new discoveries, which appear to be a major variant of SARS-CoV-2, serve as a reminder of the importance of vaccination, whether previously infected or not.

All current vaccines have been shown to provide good protection from new SARS-CoV-2 mutants. And, as Francis Collins emphasizes, adaptive immunity from vaccines provides our best hope in controlling this pandemic.

“Our greatest hope for winning this contest with viruses is to immunize as many people as possible.” Write Collins.. “It saves lives and reduces the likelihood of more mutants appearing that may circumvent protection from current vaccines.” Why the COVID-19 vaccine can provide stronger immunity than natural infections

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