How COVID-19 immunity works at this stage of the pandemic

Ohen SARS-CoV-2 was a brand new virus, it encountered little resistance in immuno-naïve hosts, i.e. us.

Vaccines, boosters and infections have increased our immunity to varying degrees. But what protection does each of these offer at this stage of the pandemic? Here’s what researchers are learning about how the human body responds to COVID-19 and its vaccines and boosters.

Vaccines generate more antibodies than infections

When the immune system encounters a new intruder like SARS-CoV-2, its first response is to produce sticky antibody proteins that attach to the virus and prevent it from binding to cells and infecting them. Viruses cannot reproduce on their own and must co-opt other cells to make more copies of themselves. Thus, the fewer viruses that can infect cells, the fewer viruses that can circulate in a person’s body and make them sick.

Vaccination is the most effective way to initiate this production of antibodies against SARS-CoV-2. Being infected with the virus itself also triggers the process, but to a lesser extent. Studies show that antibody levels against the COVID-19 virus are higher in vaccinated people than in those who are not vaccinated and are infected.

Regardless of how these antibodies are produced, they tend to decline after a few months. Still, that doesn’t mean the immune system has quit the fight.

Antibodies continue to evolve

Just as SARS-CoV-2 evolves and mutates to evade immune defences, antibodies are also improving to seek out and deactivate viruses. They achieve this in several ways. First, they become stickier in order to bind more tightly to the virus. When the immune system first encounters a virus, it may take a dozen antibodies to sufficiently neutralize it, but it may take just one evolved antibody to accomplish the same feat. “With repeated doses [of vaccine], it looks like the antibodies are improving qualitatively, not just quantitatively,” says Dr. Otto Yang, a professor of medicine at the University of California, Los Angeles. “They become more efficient.” The same is true for antibodies generated by infections, but researchers can better track the evolution of antibodies with each successive dose of a COVID-19 injection, because it’s not always obvious when people are infected.

Second, over time, the antibodies diversify and target different parts of the virus as an insurance policy against the mutations the virus generates. “The immune system also relearns,” says Ugur Sahin, co-founder of BioNTech (the company that, along with Pfizer, developed one of the COVID-19 mRNA vaccines). This process takes time, so protection against new variants is not immediate.

But, it works. Dr. David Ho, director of the Aaron Diamond AIDS Research Center at Columbia University, recently reported that people vaccinated and boosted with the original mRNA vaccines generate similar levels of antibodies against some of the new Omicron variants as people who received the updated Omicron-specific booster. This phenomenon, called immune fingerprinting, may explain why people who were vaccinated with the original shots may have decreasing levels of antibodies that make them vulnerable to infection, but once they are infected, even with the latest variants, they do not appear to develop severe COVID-19. This shows that antibodies apparently change in response to new viruses they encounter.

T-cell immunity builds up over time

Once the antibodies have stopped as many viruses as they can from infecting the cells, another population of immune cells kicks in. T cells are designed to recognize and memorize viruses in order to stop future ones more quickly. infections. T cells keep an eye out for known pathogens and arm cells capable of killing and eliminating these intruders before they cause serious illness.

With each vaccination, booster dose or infection, these T cells continue to proliferate. They not only recognize the specific virus they encounter, but, like antibodies, are also flexible enough to evolve and target less mutated parts of SARS-CoV-2. This explains why people vaccinated with the original vaccines are still well protected against serious diseases, even if they are infected with new strains of Omicron.

Past infection does not provide bulletproof immunity

Past infections can also provide some protection, but it’s not long lasting. Antibodies produced after infection peak a few months after recovery and then begin to decline (much like the initial wave of antibodies generated by vaccines). That’s why the US Centers for Disease Control and Prevention recommends people wait about three months after recovering from COVID-19 before getting a booster shot, because their immune system is already boosted and may react more. aggressively with injection side effects.

In a recent studySahin and his team reported that people infected with early Omicron variants, such as BA.1, which first appeared in late 2021, were still susceptible to infection with newer variants such as BA.4/5 , which emerged in early 2022. But even if antibodies cannot prevent infection, T cell response and antibody evolution can protect against severe COVID-19.

Immunity to COVID-19 is complex, but vaccines and boosters are still essential

Since so many people have been vaccinated, vaccinated and infected, it is difficult to say whether which component offers the best protection. And with SARS-CoV-2, immunity didn’t work the way immunologists predicted.

Usually, being infected with a given virus produces broader immunity than getting vaccinated against it. This is because when you are infected, your immune system is exposed to the whole virus and can generate defenses against any part of it. This response is generally more stratified than the limited one caused by vaccines.

However, studies of people vaccinated against COVID-19 can’t stand it. “When we compare vaccinated people to those who received one less vaccine then one breakthrough infection, people with the breakthrough infection should be better protected against another infection, but they are not,” says Sahin. “The Data show that adding a vaccine dose provides better protection than adding an infection.

The reason isn’t entirely clear, but it may have to do with the virus focusing on circumventing the existing immune response so it can continue to infect cells and spread to new hosts. Stimulating a strong immune response is not in the best interest of the virus, as it would make its primary goal of infecting more cells and making more copies of itself a challenge. Vaccines, on the other hand, are designed to kick-start a robust immune response to ensure and put immune system defenses on high alert.

However, neither previous vaccination nor infection necessarily provides protection against later strains of this ever-evolving virus. In his last paperSahin reported that people vaccinated with the Omicron booster targeting BA.4/5 showed strong levels of neutralizing antibodies against previous Omicron strains, but the same was not true for people vaccinated with a BA.1 booster. whose blood was then exposed to BA. .4/5.

There is another important difference between the protection offered by vaccines and natural infections. COVID-19 comes with a risk of symptoms, including long-lasting symptoms in the form of Long COVID. “The risk of natural infection for some infections, such as SARS-CoV-2, always outweighs the potential immune benefits,” says Dr. Egon Ozer, director of the Center for Pathogen Genomics and Microbial Evolution at the Havey Institute for Global Health at Northwestern University.

Will yearly updated COVID-19 boosters be needed?

It is clear that vaccinations and boosters will continue to play an important role in protecting against COVID-19. It will take time for the latest BA.4/5 boosters to generate the widest range of immunity via antibodies and T cells, so public health experts may need a few more months of data to decide if people will need to get additional boosters, and if so, which ones.

The good news is that since Omicron emerged in late 2021, most variants have remained in the Omicron family – mutating in different ways from the main virus, but not enough to classify a virus. entirely new branch of the SARS-CoV-2 tree.

For now, the combination of vaccines, boosters, and infections creates a type of immunity against SARS-CoV-2 that keeps most people from needing hospital care or dying. Regardless of how you generate that immunity, the good news is that the immune system “has a bit of built-in flexibility,” Ozer says. “Not all immune cells are completely identical to each other.”

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