The Immune System’s Response to Invaders such as the Coronavirus
Antibodies are an important immune response to viruses, bacteria, and other pathogens, but they aren’t the only way the body fights infection.
Booster doses are thought to improve immune protection against SARS-CoV-2, the coronavirus responsible for COVID-19.
However, other scientists wonder whether booster injections are necessary or whether our immune systems are strong enough to avoid receiving more vaccine doses.
Conversations on whether extra COVID-19 vaccine doses are needed right now have focussed on three things: breakthrough infections, declining antibody levels, and the Delta variant as some countries send out booster doses.
All of them are, of course, interconnected.
People will be less protected, especially from the highly contagious Delta form, as antibody levels fall in the months following full vaccination, raising the risk of outbreak illnesses.
Booster doses of SARS-CoV-2, the coronavirus that produces COVID-19, are seen as a strategy to shore up immune protection.
The booster shot debate, on the other hand, is more complicated.
When it comes to the effectiveness of COVID-19 vaccines over time, there isn’t just one form of effectiveness. Some vaccines may still protect the majority of individuals from becoming ill or dying, but they may provide less protection against infections that cause modest symptoms.
Furthermore, antibodies are merely one of the immune system’s tools for fighting illness. Focusing simply on antibody levels ignores the protection provided by other immune system components, some of which are more long-lasting.
Nonetheless, it’s critical to understand how antibodies work and what declining levels can indicate for COVID-19 protection.
What are antibodies?
Antibodies are Y-shaped proteins produced by the immune system as a reaction to infection. They identify and bind to certain molecular structures called antigens, such as those found on a virus or bacterium’s surface.
Many antibodies that protect against coronavirus infection attach to the virus’s surface spike protein, which the virus utilizes to invade cells.
B cells, immunological cells present in the blood, lymph nodes, spleen, and other tissues, create antibodies. A distinct type of antibody is produced by each B cell.
According to scientists, the human immune system can manufacture at least a trillion distinct antibodies, while this number could be much higher.
The B cell is triggered when the body encounters a virus or other pathogen for the first time and a B cell can bind to that infection.
When a B cell is active, it multiplies and divides into several cells, including plasma cells, which are antibody factories.
Antibodies stay in the body for months or years after infection, depending on the pathogen and other variables.
What is the difference between the adaptive and innate immune systems?
The adaptive immune system, which targets specific infections, includes B cells and antibodies.
The innate immune system is the other branch, which provides a general defense against infection.
These two branches can team up to fight a virus or bacteria before you become very ill. If your immune system has never encountered a virus or bacteria before, the innate immune response may detect something is wrong and respond promptly to an invading virus or bacteria.
This is significant because the adaptive immune system can take days to weeks to successfully build up enough antibodies to combat a given infection.
However, once your immune system has been exposed to the virus, it will be better prepared to respond faster the next time. That is, it may be able to fight off an invading bacterium or virus before you see any symptoms.
“You will develop what is called memory cells — both on the T-cell side and the B-cell side — if you have been exposed for the first time to a particular pathogen and your adaptive immune system was involved,” said Ralph Pantophlet, Ph.D., an associate professor at Simon Fraser University who studies antibody responses to HIV and other viruses.
Helper T cells are a type of T cell that induces B cells to make antibodies. Killer T cells, on the other hand, assault cells that have already been infected with a disease.
“It’s usually the antibodies that help shield or minimize that second exposure if you’re re-exposed to the same virus or one that’s extremely similar,” Pantophlet added.
How vaccines work
Vaccines stimulate the immune system in the same way as natural infection does, but without the risk of serious disease.
“[Vaccination] is essentially a ruse to equip the body with antibodies so that when you are exposed to ‘the actual thing,’ you are shielded, at least somewhat, from that assault,” Pantophlet explained.
Vaccines accomplish this by presenting an antigen from a pathogen to the immune system.
Some vaccinations include the pathogen in its whole, albeit in weakened or inactivated form. Others merely contain a portion of the pathogen.
COVID-19 mRNA vaccines instruct our cells on how to produce antibodies against the coronavirus spike protein.
What antibody level is needed?
In reaction to a disease, the immune system produces a variety of antibodies, not just one. Some of these antibodies bind to an antigen quite strongly, whereas others do not.
Antibodies can also be classified as neutralizing or non-neutralizing. Neutralizing antibodies, as the name implies, can “neutralize” a virus.
Certain neutralizing antibodies, for example, bind closely to the coronavirus spike protein and prevent it from infecting the cell in response to SARS-CoV-2.
non-neutralizing antibodies don’t do this — or only do it in a limited way — but they can still help fight viruses.
Pantophlet stated, “Non-neutralizing antibodies do not defend the cell from infection.” Non-neutralizing antibodies, on the other hand, can identify viral antigens that are exposed on the surface of infected cells.
Other sections of the immune system can come along and kill the infected cells when non-neutralizing antibodies bind to these surface antigens.
Most labs assess neutralizing antibodies for COVID-19, according to Pantophlet, “because that provides you a reasonable measure of protection [against infection].”
However, he claims that with COVID-19, we don’t yet know how high neutralizing antibody levels must be to provide some protection against infection or severe sickness.
Identifying this minimum immune response, according to Emily S. Barrett, Ph.D., an associate professor of biostatistics and epidemiology at the Rutgers School of Public Health, is difficult since the immune system has other ways of protecting you besides antibodies. This comprises the immunological response mediated by cells or T-cells.
“Unfortunately, while we would all wish to define a protection level, there is currently no easy answer,” she said.
“What we do know from just monitoring and assessing vaccine effectiveness,” Pantophlet said, “is that when the level of neutralizing antibodies declines, the risk of a breakthrough infection increases.”
Scientists have gotten closer to characterizing this protective immunological response — or “correlate of protection” — for COVID-19 in recent weeks, but we’re still not there.
In the meanwhile, scientists rely on other indicators to determine how effective immunizations are. This includes examining vaccine effectiveness in the actual world, both in specific populations and across time.
Israel took this strategy when planning to roll out COVID-19 boosters this summer.
Breakthrough infections were more common among persons who had been vaccinated earlier in the year than those who had been vaccinated more recently, according to data from the country.
Because there is no correlation of protection for COVID-19, you can’t take an antibody test to evaluate how effectively protected you are against the coronavirus following vaccination or spontaneous infection.
Waning antibody levels not surprising
Antibody levels rise after vaccination or illness but subsequently begin to drop. This is not surprising.
“Antibodies only last a limited time,” Pantophlet explained, “and how long they last are determined by a variety of biological factors.”
The number of time antibodies stays in the blood varies.
According to some studies, antibody levels against the measles virus can last for at least 10 years after two doses of the vaccination.
However, other studies have found that following the second dosage of the COVID-19 mRNA vaccine, antibody levels begin to diminish within a few weeks.
This does not result in an obvious reduction of immune protection right away.
However, research suggests that around 6 months after the second injection, the effectiveness of the Pfizer-BioNTech and Oxford/AstraZeneca vaccines begins to decline.
Pantophlet explained, “It’s apparent that once [antibody levels] start to drop to a certain level, your chances of developing a breakthrough infection increase.” “What this means is that the virus has a better chance of infecting you.”
“However, this does not always imply that you will end up in a hospital or get a serious illness,” he noted.
According to a recent Centers for Disease Control and Prevention (CDC) study, the vaccine’s overall effectiveness against hospitalization times was 86 percent 2 to 12 weeks following the second dose of an mRNA vaccine. It was 84 percent after 13 to 24 weeks.
This was not a statistically significant decline.
“It appears that your immune system as a whole — antibodies, T cells, and the other pieces that are involved — can protect you enough that you don’t necessarily wind up in the hospital,” Pantophlet said three months after receiving the COVID-19 vaccine.
“However, we have no idea — and this is a big if — if that protection will last another six months,” he continued. “That is why there is a disagreement over whether or not a booster should be given.”
Scientists are continuing to track breakthrough infections and people’s immune responses to see how long immune protection lasts after receiving COVID-19 immunization or contracting the virus naturally.
Antibodies cannot reproduce since they are proteins. Antibody-producing B cells, on the other hand, can remain in the body and reproduce as needed.
Antibodies to SARS-CoV-2 were shown to be detectable after 11 months in one research. Plasma cells in the bone marrow were also shown to be capable of generating these antibodies if needed.
According to one of the study’s authors, these cells may be capable of generating antibodies for decades.
If the coronavirus changes dramatically over that time, the immune system may need to learn to recognize and kill the new variety.
Other factors that can alter a vaccine’s effectiveness confound determining how effectively a specific antibody level protects against coronavirus infection or severe COVID-19.
The effectiveness of a vaccination refers to how well it performs in the actual world.
In contrast, its efficacy is a measure of how effectively a vaccine performs in a clinical trial. Other factors that can increase the likelihood of infection or severe sickness are taken into account by researchers during vaccine trials.
The use of a face mask or physical distancing by a vaccinated person can affect their risk of infection following immunization. Vaccine effectiveness can be influenced by community-wide masks or vaccine mandates.
According to a new study, coronavirus cases among fully vaccinated UC San Diego Health personnel increased shortly after California withdrew its mask rule in June of this year, compared to earlier in the year.
Despite this, researchers discovered that persons who were vaccinated in January and February had a higher risk of developing a breakthrough infection than people who were immunized in March and May.
A mix of these things is likely at play.
Immune response varies among people
Vaccine effectiveness in large groups is commonly studied, but people’s immune responses to vaccination and spontaneous infection might vary greatly.
Researchers discovered that patients with severe COVID-19 symptoms were more likely to have detectable antibody levels than those with mild/moderate symptoms in one investigation. Antibody levels were even lower in people who had no symptoms.
Barrett, one of the study’s authors, said, “This was a trend that appeared very immediately after infection and maintained for up to 6 months of follow-up.”
Antibody levels remained stable in the majority of research subjects for up to 6 months following infection, but they grew differently during that time based on symptoms.
Antibody levels rose rapidly in patients with severe symptoms in the first two months, but slowly in people with asymptomatic illnesses during the next six months.
The researchers did not investigate whether patients with higher antibody levels were better protected from reinfection.
“Antibodies were detectable in the great majority of infected individuals,” Barrett said, adding that “you don’t need large circulating antibody numbers to mount an infection response.”
According to another study, even patients with mild COVID-19 infections appear to be protected from reinfection for at least 6 months following infection.
One preprint study showed that diverse groups see similar declines in antibody levels after immunization.
Blood samples from 120 nursing home residents and 92 healthcare professionals who got two doses of the Pfizer-BioNTech COVID-19 vaccine were analyzed.
Antibody levels in both groups were dropped by more than 84 percent after 6 months.
The decreases were also similar in persons who had previously infected the coronavirus compared to those who were “infection-naive,” according to the researchers.
However, older persons who had never been exposed to infection had a lower first antibody response after vaccination.
Other immunizations, particularly the seasonal flu vaccine, cause a reduced immunological response in this age range.
According to research author Dr. David Canaday, a professor at Case Western University’s School of Medicine, 70% of these nursing home residents had “neutralizing [antibody] levels that were very low, near the limit of detection” six months after vaccination.
The research has yet to be peer-reviewed.
The declining antibody levels, combined with the lower starting point for nursing home residents, are especially alarming for this group, according to Canaday, because they may be weak or have other chronic health issues.
“Because of those additional diseases, this massive decline in antibodies puts them at sustained high risk, if not even higher danger,” he said. “This entails a larger chance of needing hospitalization or dying.”
People with compromised immune systems may not have a strong immunological response to vaccination, resulting in lower antibody levels at the start.
This includes organ transplant recipients, cancer patients, that suppress the immune system.
Vaccine effectiveness against hospitalization in patients with immunocompromising diseases was 63 percent across the trial period, according to the CDC.
This is why the CDC recommends that some immunocompromised persons who have received a complete dose of the mRNA COVID-19 vaccination get a booster shot.
This is not a booster shot, which is usually given when antibody levels are low. Instead, the extra dose is intended to help immunocompromised patients reach a starting point that is more comparable to the general population.
Before suggesting a second Johnson and Johnson vaccination dose for patients with weaker immune systems, the CDC is waiting for more information.
While attention has switched to the COVID-19 vaccinations’ potential for losing immunity and the need for boosters, Barrett advises that consumers keep the overall picture in mind.
“The most essential thing for the public to know is that all of the current [COVID-19] vaccinations induce a substantial antibody response,” she said. “That is without a doubt the most effective technique to avoid infection.”