作者：Ruth Jessen Hickman，医学博士；审阅者：AnjuGoel医学博士
Antibodies From Vaccines vs. Antibodies From Natural Infection Similarities and Potential DifferencesBy Ruth Jessen Hickman, MD；Medically reviewed by Anju Goel, MD, MPHUpdated on December 24, 2020
Currently, many people are interested in antibodies—proteins made by the immune system in response to an infection or vaccination. Antibody response is one of the key signs that a person was previously infected (or vaccinated) for a disease such as COVID-19. And sometimes, but not always, antibodies are a signal that an individual is protected from future infection.
What Are Antibodies?
Antibodies are proteins present on the surface of important cells of your immune system called B cells. B cells also release antibodies, partly with the help of another type of immune cell, T cells.
Role in Defeating Initial Infections
Antibodies play a key role in defeating certain types of infections. Through a variety of different mechanisms, in coordination with other parts of your immune system, some antibodies can inactivate and help eliminate pathogens. We think that includes the virus that causes COVID-19 (SARS-CoV-2).However, it takes a while for this to work. If your immune system has never dealt with a particular virus before, it won't have antibodies to the virus ready to go. Antibodies bind very precisely to a specific spot on a given virus. So it takes your immune system a while to figure out what exact antibody will work to neutralize a virus (or other type of pathogen).That's one of the reasons it takes you a while to get better after you are infected with a new virus. Depending on the specific type of antibody, it can take a couple of weeks or so to get the right antibodies produced in large amounts.A specific antibody type called IgM antibodies are usually the first to be produced. Detection of IgM antibodies can sometimes be used as a test for recent infection. For example, an IgM antibody to a specific protein is commonly used to check for recent infection with the hepatitis B virus.Other types of antibodies are usually produced a little later. A particularly important type is IgG antibodies, which tend to be more long-lived than IgM antibodies. This subtype of antibodies is critical not just for controlling initial disease but for preventing future disease if you are re-exposed in the future.
Role in Preventing Future Infections
After an infection, certain T cells and B cells that can recognize the virus stick around for a long time. If they are ever re-exposed to the virus (or other pathogen) again, these special memory cells recognize it quickly and start to respond.This helps the immune system be effective much more quickly. This way, you don't get sick. Or, if you do get sick, you usually only get a very mild version of an illness.When this happens, you are said to have protective immunity to a disease. Depending on the situation, immunity might last for months or years. You might also have partial immunity which offers you some degree of protection, (and a head start to the immune system if you get re-exposed and reinfected) but not total protection.
Antibodies in COVID-19
It's because of this key role in both treating infection and preventing disease that scientists have been so interested in the role of antibodies in COVID-19.One of the treatments being given to some COVID-19 patients as a part of clinical trials is the plasma donated from people who have recovered from the illness. The idea is that that plasma contains antibodies to the virus that might help individuals recover more quickly from infection.Researchers are also hard at work developing cutting-edge synthetic antibody therapies that might end up being an important part of treatment. Antibody products have already received Emergency Use Authorization by the FDA.5 These might be especially helpful early in the disease course.Studying how antibodies work in COVID-19 has also been critical for developing a successful vaccine. Knowledge about antibodies will be important for assessing how immunity to COVID-19—either from infection or from a vaccine—might decrease over time. From this we will learn when people might need booster vaccine shots to re-up their immunity.Even though antibodies are probably the most important means of inducing immunity in COVID-19, they may not be the only part of the immune system with an important role. For example, certain T cells play a role in protective immunity for some infections.6 This will become clearer with time.
Neutralizing vs. Non-Neutralizing Antibodies
One confusing thing is that even though antibodies are important for eliminating and preventing many kinds of infections, not all antibodies the body produces against a virus are effective.Different B cells in the body will produce multiple different antibodies that bind to different sites on the body. But only binding to some of these sites will actually inactivate the virus. For a vaccine to work, it must produce this type of neutralizing antibodies.
What About Antibodies From Natural Infection?
When you develop antibodies through natural infection, your immune system goes through this process of identifying the virus and eventually making effective antibodies. Your B cells make antibodies to different parts of the virus, some of which are effective and some of which are not. These help you eliminate the virus and recover.Hopefully, some of these antibodies also help protect you from future infection. Because the virus that causes COVID-19 is so new, there is still a lot that we don't know about it. But it seems like infection with COVID-19 gives you a relatively high degree of protection from being re-infected, at least in the short term.Very few cases of reinfection with SARS-CoV-2 have been documented worldwide. Because the virus is so widespread, if getting infected didn't give at least some protection, you'd expect many more people to have gotten the virus twice.Also, studies have indicated that people with symptoms of COVID-19 seem to produce antibodies—effective, “neutralizing” antibodies (as assessed in a lab). From our experience with other viruses, we think that that means that getting infected with COVID-19 probably leads to at least some level of protection against future infection.Additionally, studies in animals suggest at least some level of protective immunity, with at least some of this coming from antibody protection.
How Long Might Natural Immunity Last?
How long that immunity lasts is a very important question. Different types of viruses differ in how long protective immunity lasts after infection.Some viruses mutate rather quickly; when you are exposed to a new strain of the virus, your previous antibodies might not work. Immunity to some types of coronavirus may be short-lived, as people can get cold-like symptoms from certain coronaviruses season after season.But coronaviruses don't mutate as rapidly as viruses like influenza, which cause the flu. This might mean that protective immunity might last longer for COVID-19 than it does for something like the flu.Antibodies to COVID-19 do seem to decrease in the months after infection. However, that happens for all infectious diseases. It doesn't necessarily mean that immune protection is decreasing.The B cells actively releasing the relevant antibody may decrease their production in the months after an infection. But memory B cells can continue to circulate in the bloodstream for years in other types of infections. Presumably, these B cells could again start releasing the relevant antibody if they were again exposed to the virus.After they have studied a virus for a long time, scientists can establish certain standards for whether a person is immune based on laboratory standards that can be checked with a blood test (e.g., a certain concentration of a specific antibody). However, this hasn't been established for COVID-19 yet.Because the virus is so new, we'll have to see what it looks like over time. Three months after experiencing symptoms from COVID-19, one study found antibodies in the majority of people.Based on information from related viruses, some scientists estimate that immunity from natural infection might last one to three years.11 But the virus hasn't been around long enough for scientists to fully assess this. It might also make a difference whether one had an asymptomatic, mild, or a severe infection.
What About Antibodies From Vaccination?
Vaccination is a way for your body to build protective immunity without having to get sick first. Different types of vaccines do this in different ways. But in all cases, the immune system is exposed to one or more proteins from the virus (or other pathogen). That allows your immune system to make B cells that make specific antibodies that can neutralize that specific virus.The process of vaccination allows the formation of the memory B cells, just like they do in natural infection. If you are ever exposed to the virus, these B cells go into action right away and release antibodies that can target the virus. They inactivate the virus before you get sick. Or, in some cases, you might get sick but with a much milder case.That's because your immune system already has a head start, one it wouldn't have had if you hadn't been vaccinated.There are a lot of similarities but also sometimes some differences in the type of antibody and immune response you get from vaccination compared to a natural infection. As in response to a live virus, IgM type antibodies usually come first, followed by IgG and some other types of antibodies.And just like in a natural infection, protective immunity doesn't begin the moment you get vaccinated. It takes a couple of weeks or so for your immune system to form the antibodies and groups of B cells that it needs. That's why you don't get full protective coverage from a vaccination right away.For the most part, the antibodies that you form from getting vaccinated are the same kind of antibodies you would get from a natural infection. One difference is that certain types of vaccines only show the immune system part of the relevant virus. Because of that, the immune system doesn't form as many different types of antibodies as it would in the course of a natural infection.However, this doesn't mean that the antibodies formed are any less effective than those formed in a natural infection. To make a vaccine, researchers very carefully select a specific part of the virus that has been demonstrated in pre-clinical studies to trigger an antibody response that effectively neutralizes the virus. It's just that theoretically, someone who has been naturally infected might also have additional antibodies (many of which might be ineffective).Sometimes researchers can use this understanding to help make diagnostic decisions. For example, differences in certain antibodies can sometimes be used to determine if a person has an active or chronic infection with hepatitis B or if they have been successfully vaccinated. People who got the antibodies through natural infection have a specific antibody not found in people who got vaccinated (one not important for developing immunity).Most of the vaccines under development for COVID-19 only show the immune system part of the virus, a protein chosen to prime a strong immune response. (This includes the Pfizer mRNA vaccine.) So, someone who had naturally been infected with the virus might have some additional antibody types not found in someone who had been successfully vaccinated.COVID-19 Vaccines: Stay up to date on which vaccines are available, who can get them, and how safe they are.
Assessing Differences in Natural vs. Vaccine-Induced Immunity
In fact, an important topic for researchers are these potential differences in the protective immune response (including antibodies) between people who got an infection naturally and people who got a vaccine.It is a very complex topic. You can't just compare natural infection to vaccination, because not every vaccine has the same properties, and not every vaccine will trigger exactly the same immune response.In some cases, a specific vaccine might not provide as effective of an antibody response as being naturally infected. But other times, the reverse might be the case, especially if a vaccine has been especially designed to provoke a strong response. We can't make assumptions without studying the specific data over the long-term.
Potential Risks of Antibodies
We usually think about the benefits of antibodies in terms of eliminating infections and providing protective immunity. However, in rare circumstances, binding of an antibody might actually worsen an infection. For example, antibodies might bind to a virus in such a way that help it enter cells more easily.This might mean that a person re-infected after an initial mild infection might then have more severe disease. Or, it theoretically might mean that a person could have a worse response to a potential infection with COVID-19 if they have previously been vaccinated for the disease.This scenario has been called “antibody dependent enhancement.”It has been found in viruses such as dengue, in which it complicated the creation of successful vaccines. In some (but not all) animal studies, it has also been observed in a coronavirus closely related to the one that causes COVID-19—the virus that causes SARS.Because they were aware of this theoretical possibility, researchers have been looking very carefully to see whether this might be a possibility in COVID-19. However, no signs of antibody dependent enhancement have been found in COVID-19.This includes pre-clinical studies and clinical studies that have now included well over 100,000 patients. This has been very reassuring to researchers, but they will continue to monitor for this possibility.This includes the Pfizer mRNA vaccine for COVID-19, the only vaccine as of mid-December 2020 that has been released under an Emergency Use Authorization by the FDA. Researchers will continue to monitor the effects of this vaccine and the others under development. With time, we'll get more data that will hopefully definitively quash this theoretical concern.We'll also continue to learn how immunity and the antibody response changes over time—both after natural infection and after vaccination with different types of COVID-19 vaccines.
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