Skip to main content

How Immunity Generated from COVID-19 Vaccines Differs from an Infection

Posted on by

Orginal viral spike is shown binding to antibody from vaccine and from infection. Variant spikes only bind to antibody from vaccine.

A key issue as we move closer to ending the pandemic is determining more precisely how long people exposed to SARS-CoV-2, the COVID-19 virus, will make neutralizing antibodies against this dangerous coronavirus. Finding the answer is also potentially complicated with new SARS-CoV-2 “variants of concern” appearing around the world that could find ways to evade acquired immunity, increasing the chances of new outbreaks.

Now, a new NIH-supported study shows that the answer to this question will vary based on how an individual’s antibodies against SARS-CoV-2 were generated: over the course of a naturally acquired infection or from a COVID-19 vaccine. The new evidence shows that protective antibodies generated in response to an mRNA vaccine will target a broader range of SARS-CoV-2 variants carrying “single letter” changes in a key portion of their spike protein compared to antibodies acquired from an infection.

These results add to evidence that people with acquired immunity may have differing levels of protection to emerging SARS-CoV-2 variants. More importantly, the data provide further documentation that those who’ve had and recovered from a COVID-19 infection still stand to benefit from getting vaccinated.

These latest findings come from Jesse Bloom, Allison Greaney, and their team at Fred Hutchinson Cancer Research Center, Seattle. In an earlier study, this same team focused on the receptor binding domain (RBD), a key region of the spike protein that studs SARS-CoV-2’s outer surface. This RBD is especially important because the virus uses this part of its spike protein to anchor to another protein called ACE2 on human cells before infecting them. That makes RBD a prime target for both naturally acquired antibodies and those generated by vaccines. Using a method called deep mutational scanning, the Seattle group’s previous study mapped out all possible mutations in the RBD that would change the ability of the virus to bind ACE2 and/or for RBD-directed antibodies to strike their targets.

In their new study, published in the journal Science Translational Medicine, Bloom, Greaney, and colleagues looked again to the thousands of possible RBD variants to understand how antibodies might be expected to hit their targets there [1]. This time, they wanted to explore any differences between RBD-directed antibodies based on how they were acquired.

Again, they turned to deep mutational scanning. First, they created libraries of all 3,800 possible RBD single amino acid mutants and exposed the libraries to samples taken from vaccinated individuals and unvaccinated individuals who’d been previously infected. All vaccinated individuals had received two doses of the Moderna mRNA vaccine. This vaccine works by prompting a person’s cells to produce the spike protein, thereby launching an immune response and the production of antibodies.

By closely examining the results, the researchers uncovered important differences between acquired immunity in people who’d been vaccinated and unvaccinated people who’d been previously infected with SARS-CoV-2. Specifically, antibodies elicited by the mRNA vaccine were more focused to the RBD compared to antibodies elicited by an infection, which more often targeted other portions of the spike protein. Importantly, the vaccine-elicited antibodies targeted a broader range of places on the RBD than those elicited by natural infection.

These findings suggest that natural immunity and vaccine-generated immunity to SARS-CoV-2 will differ in how they recognize new viral variants. What’s more, antibodies acquired with the help of a vaccine may be more likely to target new SARS-CoV-2 variants potently, even when the variants carry new mutations in the RBD.

It’s not entirely clear why these differences in vaccine- and infection-elicited antibody responses exist. In both cases, RBD-directed antibodies are acquired from the immune system’s recognition and response to viral spike proteins. The Seattle team suggests these differences may arise because the vaccine presents the viral protein in slightly different conformations.

Also, it’s possible that mRNA delivery may change the way antigens are presented to the immune system, leading to differences in the antibodies that get produced. A third difference is that natural infection only exposes the body to the virus in the respiratory tract (unless the illness is very severe), while the vaccine is delivered to muscle, where the immune system may have an even better chance of seeing it and responding vigorously.

Whatever the underlying reasons turn out to be, it’s important to consider that humans are routinely infected and re-infected with other common coronaviruses, which are responsible for the common cold. It’s not at all unusual to catch a cold from seasonal coronaviruses year after year. That’s at least in part because those viruses tend to evolve to escape acquired immunity, much as SARS-CoV-2 is now in the process of doing.

The good news so far is that, unlike the situation for the common cold, we have now developed multiple COVID-19 vaccines. The evidence continues to suggest that acquired immunity from vaccines still offers substantial protection against the new variants now circulating around the globe.

The hope is that acquired immunity from the vaccines will indeed produce long-lasting protection against SARS-CoV-2 and bring an end to the pandemic. These new findings point encouragingly in that direction. They also serve as an important reminder to roll up your sleeve for the vaccine if you haven’t already done so, whether or not you’ve had COVID-19. Our best hope of winning this contest with the virus is to get as many people immunized now as possible. That will save lives, and reduce the likelihood of even more variants appearing that might evade protection from the current vaccines.

Reference:

[1] Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection. Greaney AJ, Loes AN, Gentles LE, Crawford KHD, Starr TN, Malone KD, Chu HY, Bloom JD. Sci Transl Med. 2021 Jun 8.

Links:

COVID-19 Research (NIH)

Bloom Lab (Fred Hutchinson Cancer Research Center, Seattle)

NIH Support: National Institute of Allergy and Infectious Diseases

254 Comments

  • steve says:

    . . . The disease acquired immunity lasts decades (as per last SARS data) and is broad spectrum: far broader then the spikes and it variants. It is far better and safer to have had the disease than the vaccines. Vaccines are already failing as per Israel data.

    • Stuart says:

      Absolutely numerous studies and real life scenarios in places of high viral load, hospitals etc, show that natural infection is robust and better in the mucosa. Immunity is waning in some vaccinated which is a problem, caveat is it depends on the individual. We also have long lasting T-cell immunity as well, something which is being looked into with the new gen of vaccines, literally based on a good natural immunity….and for those that need them, because not everyone does.

      • Cammy says:

        So are you advocating getting Covid as a way to be protected? I think the basic point is that, for those who want to argue they don’t need the vaccine because they’ve ALREADY had Covid (not a plan to get Covid in lieu of the vaccine…which would be risking death, no matter what age and even with no comorbidities) it doesn’t make sense to avoid another method of protection with a different set of possibly more spike protein specific antibodies. We can’t tell what targets your body’s antibodies are targeting when you have had an infection. At least by getting vaccinated as well you know that you have antibodies produced against a high-yield target–the flag waving spike protein.

        • C.R. says:

          Save lives by giving covid-19 vaccines to those who have not had covid-19 and have not been vaccinated who may catch it and either die or be hospitalized. GIVE number of people who have had covid-19 and either died or who have been hospitalized versus the number of people who have not have not had covid-19 or one of the vaccines: Sputnik V, Astra Zeneca, Moderna, J&J or Pfizer. Obvious who should be vaccinated UNTIL everyone has either had Covid-19 and survived OR been vaccinated.

    • superkuh says:

      Intramuscular vaccination for respiratory viruses does not provide long lasting immunity to the surface mucosa tissues of the upper respiratory tract. The IgG antibodies in body serum do seep into the lower lungs and provide robust protection from serious disease, but they do not prevent infections very long in the nose, sinuses, or throat. This is the disparity many studies are now highlighting but failing to acknowledge the cause of. Intramuscular vaccinations are the *most important first step *and will keep hospitalization down. But the required next step is intranasal vaccination to recruit B and T cells to the upper respiratory mucosa and have the B cells produce local IgA antibodies. This would actually stop infections (infections defined from nasal swab testing).

      It is up to the NIH and other large organizations in the world to get this messaging out there. There are two types of “breakthrough”. There’s the fact that intramusculars don’t protect the upper respiratory mucosa, and then there’s when sars-cov-2 actually manages to infect body organs and the lower lungs. They are entirely different things.

      The variants currently circulating don’t play a huge role in this discrepancy. We’d be seeing the same amount of upper respiratory mucosa infections (without hospitalization) even if there were no Delta and it was just alpha/beta/gamma or even original wuhan sequence sars-cov-2 . . .

      • D Hart MD says:

        There was an article in the NIH blog from August 19, 2021 titled “Intranasal COVID-19 vaccine effective in animal studies,” so work is progressing on that front.

        Regarding your concluding statement, “We’d be seeing the same amount of upper respiratory mucosa infections (without hospitalization) even if there were no Delta and it was just alpha/beta/gamma or even original wuhan sequence sars-cov-2 . . .” I disagree. Delta is 60% more contagious than Alpha and twice as contagious as the original strain. With increased contagiousness there will be an increase in the number of infections (such as we’re seeing now).

      • john Smith says:

        Large Israeli study: Natural immunity provides 13 times more protection against Delta than Pfizer’s vaccine does

  • Michael says:

    Viral load is throughout the body, especially in the gestational system. Covid is in feces. Natural infection is much more robust than a so called vaccine that only fights the spike protein. The immune system is so much more. My father’s cancer doc, one of very few recommended he didn’t have the vaccine but instead take an antibody test and t cell test, as he had covid in 2020. He’s had several tests and all show a immune response over 12 month after infection. Now look at the data in Israel, people are loosing immunity after 4 months….

    • Kirby U. says:

      If you’re lucky, the vaccine will protect you. If you still get infected, you have a shot at gaining natural immunity.

      However, ignoring the opportunity of a vaccine and risking getting serious covid with lasting effects, because natural immunity is better, is not a calculation I’d recommend to anybody. Maybe you would.

      I have no regrets getting vaccinated and still have an intact immune system ready to fight the virus, any variant.

    • Lorri Lester says:

      What kind of antibody, monoclonal therapy? It is suppose to be out of your system in 6 months max. Is this the same as your father took?

  • G. Ching says:

    As a retired pediatrician, I want to remind everyone that pediatric vaccines were required to protect kids from diseases with high rates of morbidity/mortality. Covid-19 does not pose that kind of risk in young people. Perhaps effective herd immunity would be better served if we did not immunize the younger generation, but instead allow them to develop natural immunity from actual viral exposure. Unfortunately, there would of course be some who would suffer serious disease.

    • Joanne M Giannini says:

      G. Ching – The U.K. agrees with you. At this point in time, they are NOT recommending vaccination for kids until more data is available about the longer-term effects of the shots (i.e., heart inflammation) unless there are underlying risk factors like diabetes. And the risk to kids with pre-existing natural immunity from COVID is much less. And yet, no pass for them either. The whole situation makes no logical sense. Risk versus reward has been totally disregarded.

  • Joanne M Giannini says:

    Question for all the scientists on this blog. Just finished reading a study entitled “The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147-receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease” which was posted on July 20, 2021. The study stated that “In conclusion, although more investigation being needed to definitively prove the harmful effects of the S protein on the heart vascular pericytes (PCs) and associated microvasculature in vivo, this work suggests that fragments of the S protein may elicit vascular cell dysfunction through CD147, independently from the infection. This mechanism has the potential to spread cellular and organ injury beyond the infection sites and may have important clinical implications. For instance, in patients with disrupted endothelial barrier and increased vascular permeability due to underlying diseases, such as hypertension, diabetes, and severe obesity, S protein molecules could easily spread to the PC compartment and cause, or exacerbate, microvascular injury.”

    To me it appears that this paper proves that the spike protein itself is a toxin and a pathogenic protein independent of an infection. I understand that this study pertains to the actual virus, but considering that the current vaccines result in your body actually making the S protein, how would the vaccinations not result in people being innoculated with a toxin if it gets into their circulation (which has been shown to happen by a Japanese study)? And when that happens, wouldn’t it stand to reason that it would cause damage in the cardiovascular system? I’m seriously curious to know what mechanism ensures that cardiovascular damage via microclots does not occur via the vaccines and hoping someone more knowledgeable than me can help clear this up.

    • JR says:

      I wonder if that could explain the following. Yesterday, I stopped by an old neighbor’s house who was hosting a small gathering. One of the gent’s there was from a church our family had attended for years. He used to work at UC Berkeley as a scientist and had worked in virology. I confirmed with him my understanding that science has always recognized immunity acquired from surviving a disease. I also said to him that I had heard the risk of the COVID vaccines for people who had recovered from the disease is higher than for those who have never had the disease. At this point, he asked me if I had heard about a couple from the church ( I will not share their names here.) I told him no. He said they both had COVID and recovered. He said about three months after they recovered they took the Pfizer vaccine. He said they did OK with the first dose and the husband did OK with the second dose. The wife died suddenly the day after receiving the second dose. He said her doctor said it had nothing to do with the vaccine because she had comorbidities like high blood pressure, and did not have an autopsy performed. I wonder how many other stories like this are out there that do not show up in the side effect records . . .

    • D Hart MD says:

      Ms. Giannini, I recommend that you look at a video on YouTube titled “Will Vaccine Generated Spike Proteins Bind To Our Cells?” from January 4 of this year. This helps to explain how little to no spike protein is in circulation after a vaccination with mRNA vaccines. It’s 37 minutes long but worth the time, IMO.

      • Joanne M Giannini says:

        Dr. Hart – Thanks for the video tip. I LOVE Dr. Mobeen! I listen to his lectures all the time. But I believe the video you are referencing is out of date. You should check into all the more recent comments on that video. Hundreds of medical researchers and professionals question him on his stance in this video and raise some serious concerns. Comments like “The spike protein, whether from the virus or the vaccine, has the potential to cause prion-like protein deformities that will cause brain diseases in a few years. The difference is the vaccine spike protein is manufactured wherever the mrna can reach in the bloodstream and lymphatic system once injected, whereas the virus usually only affects the mucosal membranes of the upper sinus. Our body’s line of defense to the spike protein is bypassed with the injection. Spike protein is formed at random in the body with the injection. The potential for blood clots and prion like diseases is greatly increased with the injection.

        Dendritic cells are situated in the upper respiratory tract almost outside the organism, on the boundary. There are no dendritic cells inside the blood vessels! Dendritic cells are the key for the regulated adaptive immune response, but in this case they are just skipped. Inside the blood vessels – nature has never seen a spike protein or a respiratory virus or anything similar. Dendritic cells will not and could not present the vaccine generated spike protein. It will only be presented by endothelial cells (those that line the blood vessels from the inside) in the context of MHCI and therefore will activate T8 cells in an unregulated manner, leading to destruction of blood vessels by primed T8 cells. This will happen all over the body including brain, leading to disseminated blood clotting, clotting system exhaustion and consequential bleeding from all organs and skin and brain clots. The unregulated activation of T8 cells will remain as inadequate over-reactive memory, that will mount a hyper-reactive adaptive response upon a future encounter with any coronavirus (there are 100+ strains that infect humans) which will cause atomic bomb like immune reaction that will destroy lungs. The risk is even higher with revaccination.” I just wish there was more clear data and large-scale studies on this subject, as well as the issue of vaccine safety relative to recovered individuals.

        • Francesca Stracke says:

          Worse Than the Disease? Reviewing Some Possible Unintended Consequences of the mRNA Vaccines Against COVID-19 | International Journal of Vaccine Theory, Practice, and Research (ijvtpr.com) Vol 2(1) May 10, 2021, p 38-79. Stephanie Seneff from MIT and this is my favorite statement from the article: “Many who test positive for COVID-19 express no symptoms. The number of asymptomatic, PCR positive cases varies widely between studies, from a low of 1.6% to a high of 56.5% … Those who are insensitive to COVID-19 probably have a very strong innate immune system. The healthy mucosal barrier’s neutrophils and macrophages rapidly clear the viruses, often without the need for any antibodies to be produced by the adaptive system. However, the vaccine intentionally completely bypasses the mucosal immune system, both through its injection past the natural mucosal barriers and its artificial configuration as an RNA-containing nanoparticle…those with a strong innate immune response almost universally experience either asymptomatic infection or only mild COVID-19 disease presentation. Nevertheless, they might face chronic autoimmune disease, as described previously, as a consequence of excessive antibody production in response to the vaccine”

  • Megan Herbert says:

    This seems to be the opposite result of the real world study out of Israel. The study was robust with over 670,000 patients that were real live humans being exposed to the real Delta variant. Immunity from COVID infection was far greater than the vaccinated immunity coverage. Durability of the vaccines begins to wane after six months with breakthrough infection 4-8%, yet reinfection remains very low at <1%. How can you suggest from a lab study that immunity from infection is less effective than vaccine immunity, when real-world data suggests otherwise? They are both immunity. Avoiding infection is the goal-so if you have not gotten COVID the vaccine offers protection without risk of severe illness; if you have got infected already a natural immune response is protective. Why is the US so afraid to say this?

    • Joanne says:

      100% agree with you

    • Travis Ambler says:

      People will use it as a reason not to get vaccinated.

      • Joanne M Giannini says:

        I believe that people actually will use the fact that natural immunity is NOT recognized as a reason to not get vaccinated, the reason being that it feeds into the whole “conspiracy theory” narrative. Since there are NUMEROUS studies indicating that natural immunity is robust and durable, the complete ignorance of the issue by the government is building major distrust. If natural immunity was recognized, it would go a LONG way towards correcting vaccine hesitancy in individuals without any immunity, which should be the concern – not forcing vaccination on individuals who already have demonstrated natural immunity.

  • Steve Barger says:

    Is anyone going to address the issue of dosage? The data in this paper come from people who received two injections of the Moderna vaccine at 250 μg each. The Moderna vaccine is actually administered at 100 μg, and the Pfizer vaccine is administered at 30 μg. What relevance do these data have to real-world vaccinations?!

    • D Hart MD says:

      Good catch. However, from the original article, “The majority of our study focused on 14 individuals who received the 250-μg dose, although we validated key conclusions with a smaller subset of eight trial participants who received the 100-μg dose.”

      • JR says:

        Being that the government is pushing hard at forcing everyone to be vaccinated, by isolating non vaccinated citizens and barring them from going places, notwithstanding the science showing there is no benefit in vaccinating COVID survivors, and ignoring that COVID survivors are at higher risk of serious side effect from the vaccines, has anyone found which vaccine is the least risky for COVID survivors? I personally know a COVID survivor who died the day after the second dose of the Pfizer vaccine, so that one is definitely out for my wife and I. One of our relatives who researched the subject chose the J & J vaccine. He said that one is based on what vaccines for quite some time have been based on, as opposed to the experimental mRNA vaccines. I would sure love to hear from all of you who are truly knowledgeable on the pros and cons, as opposed to those who are simply highly opinionated vaccine zealots.

        • Lisa says:

          Well watch the J&J, we had a friend who died in his yard the day after getting that shot. I personally finally caved to pressure and got two Pfizer shots. The second one was two weeks ago. I was great with the first one but with the second I didn’t ‘feel right’ for a little over a week. I went to the ER five days after getting the 2nd one because my heart rate was all over the place. I also got a blood blister looking type of thing on my gums above my front tooth. However, all of my test results came back okay in the ER. My husband thinks it was anxiety but I had none of that with the first shot.I workout and walked 3 miles and lifted weights after both shots the first night, but after the second one started making me feel bad, I quit working out. I’ll start again this week.

          I had covid in January and still had antibodies in August-tested through my doctors office. I still can not taste and smell 9 months later. Pressure came from family members for me to ‘protect the kids and next generation’.
          If anything…I wish I would have stopped at the first shot and left it at that…or not gotten at all. I feel like I put another chemical man made experiment into my body.

          Good luck with your choice, it is an extremely hard one to make for each of us as individuals. I wish the gov’t would understand we are ALL different. Different weight, height, health conditions, no health conditions. I asked the nurse giving my shot if I could have a smaller dose since I’m 5′ and 100lbs. She said I give the same dose to a 12 year old as I do a 200+ lb man. I said don’t you think that is weird? She just shrugged her shoulders.

        • Joanne M Giannini says:

          JR – I am getting my antibodies checked regularly via SARS-CoV-2 Semi-Quantitative Total Antibody (Spike) test. It quantifies the level of detectable antibodies against the SARS-CoV-2 spike protein receptor binding domain (RBD). From what I have seen coming out of the Israel studies, it appears that 50 AU/mL is protective against transmission (note that this does not take into account T-Cell immunity, which would be protective against serious disease). IF my antibodies drop below that level, I would CONSIDER getting the Novavax vaccine at that time (due to be out this winter), but I would want to wait a bit and see if real world data ends up matching up with the trial results. A protein-subunit approach used by Novavax was first implemented for the hepatitis B vaccine, which has been used in the U.S. since 1986. The pertussis vaccine, which is required for almost all children in U.S. public schools, is also made this way. The Novavax vaccine also appears to have a substantially lower rate of side effects than the currently authorized mRNA and adenovector vaccines . . .

          Speaking of Israel studies, be sure to check out the preprint study “Large-scale study of antibody titer decay following BNT162b2 mRNA vaccine or SARS-CoV-2 infection” published on August 22, 2021. The results state that “A total of 2,653 individuals fully vaccinated by two doses of vaccine during the study period and 4,361 convalescent patients were included. Higher SARS-CoV-2 IgG antibody titers were observed in vaccinated individuals (median 1581 AU/mL IQR [533.8-5644.6]) after the second vaccination, than in convalescent individuals (median 355.3 AU/mL IQR [141.2-998.7]; p<0.001). In vaccinated subjects, antibody titers decreased by up to 40% each subsequent month while in convalescents they decreased by less than 5% per month. Six months after BNT162b2 vaccination 16.1% subjects had antibody levels below the seropositivity threshold of <50 AU/mL, while only 10.8% of convalescent patients were below <50 AU/mL threshold after 9 months from SARS-CoV-2 infection." This is one of the main studies that served as the basis for the introduction of booster shots in Israel – and the same data that the FDA used to evaluate their decision on booster shoots. Why is the CDC/NIH cherry picking data from these studies? They believe the results of this study are good enough to recognize the need for boosters for millions of people, but not to recognize the durability of natural immunity for around 100+ million Americans.

  • Anna says:

    Except multiple people that I know who have had the shots are coming down with Covid in spite of it. None of them have died from it, so I guess I could conclude that the vaccine saved them, except for all of the people I know that did not have the shots equally recovered just as well. That’s just my small sampling of course, we all know of someone who didn’t make it and that keeps our focus.

    The only difference I recently noticed is that my very good friend and her husband who both took the Phizer shot, were able to get out and about and potentially spread it around more in the beginning before they recognized they were coming down with Covid. She now feels guilty for not recognizing she was ill until it really hit her after a few days.

    • D Hart MD says:

      In those with an SARS-CoV-2 infection, asymptomatic transmission occurs irrespective of one’s vaccination status. Search for “Asymptomatic SARS-CoV-2 infection: A systematic review and meta-analysis” on the website of the Proceedings of the National Academy of Sciences (PNAS) from August 24, 2021. Their study showed that of those infected, those with confirmed, asymptomatic infections (not presymptomatic, but truly asymptomatic) comprised anywhere from 20% (elderly) to 47% (children) of the infections.

      Also, those who have breakthrough infections appear to have less viable virus and are contagious for a shorter period of time, relative to an unvaccinated person with an SARS-CoV-2 infection.

  • D Hart MD says:

    Interesting article from September 3, 2021 on the website of the American Association for the Advancement of Science (with a link to the original study at Science Advances) titled “Some COVID-19 Survivors May Be Better Protected From Variants Than Others” showing the sera of those who had recovered from relatively severe SARS-CoV-2 infections (as well as those who had been vaccinated) had good responses to the alpha, beta and gamma variants (Delta was not particularly prominent at the time of the study). However, the sera of those with mild infections “often showed no response to the beta and gamma variants.”

  • 1 2 3

Leave a Comment