https://directorsblog.nih.gov/2021/06/22/how-immunity-generated-from-covid-19-vaccines-differs-from-an-infection/ Skip to main content NIH Director's Blog Subscribe Search [ ] [ ] Search Only Director's Album Toggle navigation * NIH.gov * Blog Home * Director's Album How Immunity Generated from COVID-19 Vaccines Differs from an Infection Posted on June 22nd, 2021 by Dr. Francis Collins 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 Share this: * Click to share on Facebook (Opens in new window) * Click to share on Twitter (Opens in new window) * More * * Click to share on LinkedIn (Opens in new window) * Click to share on Pinterest (Opens in new window) * * Click to share on Tumblr (Opens in new window) * Click to share on Reddit (Opens in new window) * * Click to share on Pocket (Opens in new window) * Click to share on Telegram (Opens in new window) * * Click to share on WhatsApp (Opens in new window) * Click to share on Skype (Opens in new window) * * Click to email this to a friend (Opens in new window) * Click to print (Opens in new window) * * Related Posted In: News Tags: ACE2, acquired immunity, anitbodies, common cold, coronavirus, COVID-19, COVID-19 infections, COVID-19 vaccine, deep mutational scanning, Moderna vaccine, mRNA vaccine, novel coronavirus, pandemic, RBD, receptor binding domain, SARS-CoV-19 variants, SARS-CoV-2, spike protein, vaccines, variants of concern 224 Comments * steve says: August 22, 2021 at 2:42 pm . . . 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. Reply + Stuart says: August 23, 2021 at 5:19 pm 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. Reply + superkuh says: August 26, 2021 at 2:16 pm 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 . . . Reply << Previous 1 2 3 Leave a Comment Cancel reply Recent Items * The Amazing Brain: Tracking Molecular Events with Calling Cards August 24, 2021 * Thanking NIH's Call Center and Contact Investigation Teams August 18, 2021 * The Amazing Brain: A Sharper Image of the Pyramidal Tract August 17, 2021 * The Amazing Brain: Visualizing Data to Understand Brain Networks August 10, 2021 * A Gala Event for Down Syndrome August 9, 2021 Blog Archives Blog Archives [Select Month ] About the NIH Director Francis S. Collins, M.D., Ph.D. Francis S. Collins, M.D., Ph.D. Appointed the 16th Director of NIH by President Barack Obama and confirmed by the Senate. He was sworn in on August 17, 2009. On June 6, 2017. President Donald Trump announced his selection of Dr. Collins to continue to serve as the NIH Director. More about Dr. Collins @NIHDirector on Twitter A small study of patients w/ breathing problems 3+ months after hospitalization for #COVID19 suggests that... https://t.co/TDxWXBCz5L 1 day ago Join us tomorrow for an #NIH Music & Health event. We'll discuss evidence-based music therapies for brain disorders... https://t.co/ ozbXHqPkw2 2 days ago A new technology enables neuroscientists to track key interactions between the #genome and essential proteins in th... https://t.co/ IncuWGlGNc 2 days ago Follow @NIHDirector NIH On Facebook [NIH_FBImag] Follow on Facebook Blog Info Editor Kendall Morgan, Ph.D. Comments and Questions If you have comments or questions not related to the current discussions, please direct them to Ask NIH. You are encouraged to share your thoughts and ideas. 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