https://directorsblog.nih.gov/2021/05/18/human-antibodies-target-many-parts-of-coronavirus-spike-protein/ Skip to main content NIH Director's Blog Subscribe Search [ ] [ ] Search Only Director's Album Toggle navigation * NIH.gov * Blog Home * Director's Album Human Antibodies Target Many Parts of Coronavirus Spike Protein Posted on May 18th, 2021 by Dr. Francis Collins Viral spike with labels Receptor-binding domain (RBD) antibody, N-terminal domain (NTD) antibody, S2 subunit antibodyCaption: People who recovered from mild COVID-19 infections produced antibodies circulating in their blood that target three different parts of the coronavirus's spike protein (gray). Credit: University of Texas at Austin For many people who've had COVID-19, the infections were thankfully mild and relatively brief. But these individuals' immune systems still hold onto enduring clues about how best to neutralize SARS-CoV-2, the coronavirus that causes COVID-19. Discovering these clues could point the way for researchers to design highly targeted treatments that could help to save the lives of folks with more severe infections. An NIH-funded study, published recently in the journal Science, offers the most-detailed picture yet of the array of antibodies against SARS-CoV-2 found in people who've fully recovered from mild cases of COVID-19. This picture suggests that an effective neutralizing immune response targets a wider swath of the virus' now-infamous spike protein than previously recognized. To date, most studies of natural antibodies that block SARS-CoV-2 have zeroed in on those that target a specific portion of the spike protein known as the receptor-binding domain (RBD)--and with good reason. The RBD is the portion of the spike that attaches directly to human cells. As a result, antibodies specifically targeting the RBD were an excellent place to begin the search for antibodies capable of fending off SARS-CoV-2. The new study, led by Gregory Ippolito and Jason Lavinder, The University of Texas at Austin, took a different approach. Rather than narrowing the search, Ippolito, Lavinder, and colleagues analyzed the complete repertoire of antibodies against the spike protein from four people soon after their recoveries from mild COVID-19. What the researchers found was a bit of a surprise: the vast majority of antibodies--about 84 percent--targeted other portions of the spike protein than the RBD. This suggests a successful immune response doesn't concentrate on the RBD. It involves production of antibodies capable of covering areas across the entire spike. The researchers liken the spike protein to an umbrella, with the RBD at the tip of the "canopy." While some antibodies do bind RBD at the tip, many others apparently target the protein's canopy, known as the N-terminal domain (NTD). Further study in cell culture showed that NTD-directed antibodies do indeed neutralize the virus. They also prevented a lethal mouse-adapted version of the coronavirus from infecting mice. One reason these findings are particularly noteworthy is that the NTD is one part of the viral spike protein that has mutated frequently, especially in several emerging variants of concern, including the B.1.1.7 "U.K. variant" and the B.1.351 "South African variant." It suggests that one reason these variants are so effective at evading our immune systems to cause breakthrough infections, or re-infections, is that they've mutated their way around some of the human antibodies that had been most successful in combating the original coronavirus variant. Also noteworthy, about 40 percent of the circulating antibodies target yet another portion of the spike called the S2 subunit. This finding is especially encouraging because this portion of SARS-CoV-2 does not seem as mutable as the NTD segment, suggesting that S2-directed antibodies might offer a layer of protection against a wider array of variants. What's more, the S2 subunit may make an ideal target for a possible pan-coronavirus vaccine since this portion of the spike is widely conserved in SARS-CoV-2 and related coronaviruses. Taken together, these findings will prove useful for designing COVID-19 vaccine booster shots or future vaccines tailored to combat SARS-COV-2 variants of concern. The findings also drive home the conclusion that the more we learn about SARS-CoV-2 and the immune system's response to neutralize it, the better position we all will be in to thwart this novel coronavirus and any others that might emerge in the future. Reference: [1] Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes. Voss WN, Hou YJ, Johnson NV, Delidakis G, Kim JE, Javanmardi K, Horton AP, Bartzoka F, Paresi CJ, Tanno Y, Chou CW, Abbasi SA, Pickens W, George K, Boutz DR, Towers DM, McDaniel JR, Billick D, Goike J, Rowe L, Batra D, Pohl J, Lee J, Gangappa S, Sambhara S, Gadush M, Wang N, Person MD, Iverson BL, Gollihar JD, Dye J, Herbert A, Finkelstein IJ, Baric RS, McLellan JS, Georgiou G, Lavinder JJ, Ippolito GC. Science. 2021 May 4:eabg5268. Links: COVID-19 Research (NIH) Gregory Ippolito (University of Texas at Austin) NIH Support: National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Institute of General Medical Sciences; National Center for Advancing Translational Sciences 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: antibodies, coronavirus, coronavirus vaccine, COVID-19, COVID-19 immune response, immunology, mild COVID-19, N-terminal domain antibody, novel coronavirus, pandemic, RBD, receptor binding domain, receptor-binding domain antibody, S2 subunit antibody, SARS-CoV-19 variants, SARS-CoV-2, spike protein, structural biology, vaccine design 14 Comments * Lisa Phillip Rimland says: May 18, 2021 at 10:14 am This is an amazing study, thank you for posting Dr. Collins, I have been wondering about the possible beneficial immunological effects of having had mild Covid. This study gives us a bigger picture regarding the body's response to Covid, and possibly more insights regarding the design of vaccines and boosters, and gives us hope for the future. Reply + Africa so says: May 19, 2021 at 9:49 pm It looks like from his finding that obtaining an immunity from actually acquiring the Covid 19 infection is better because the antibodies produced target all parts of the spike protein rathr that the targeted RBD portion by the vaccine. With the vaccine, herd immunity will never be achieved because the NTD portion will allow the virus to continue mutating. Reply * Andrew Goldstein says: May 18, 2021 at 12:01 pm Has SARS-CoV-2 antibody cross reactivity been observed with either other viral epitopes or with host antigens? I ask this because the former could be beneficial and the latter detrimental, causing harmful autoimmune reactions. Autoimmune diseases can be triggered by other viral infections or genetic predisposition. Reply * Gary S. says: May 18, 2021 at 12:47 pm How long do the anti-bodies continue once the covid illness is diminished after contracting it? I don't think I need the vaccine since I had the virus in November '20. Reply + Debra Smallwood says: May 18, 2021 at 4:35 pm I had mild covid March 1st of this year. How long do these antibodies protect you from getting covid again? Reply * John Hasty BS, MT(ASCP) Retired says: May 18, 2021 at 1:42 pm The antibodies to the Coronavirus "Target" many antigenic sites including those of the Spike Protein. Everyone is pushing information about the Spike Protein because that the antigen used in the current vaccines. I see only a unified narrow minded point of view and wonder why. Reply * Dr. Imtiyaz says: May 18, 2021 at 1:51 pm The reduction in infection and development of antibodies in response to mild COVID infection in patients with single jab of 20 to 30 days is evident with various amounts of symptomatic relief and recovery. Reply * LA Smith says: May 18, 2021 at 4:04 pm My question is why does big pharma always go for megadollar super cures without adequately exploring chemical entities shelved in years past? I am aware that some effort was made, but not enough. In an emerging crisis, shouldn't quicker, cheaper cures the public can access in a drug store be looked at? Big pharma will always attempt to maximize profits while the public is left hanging. Do we really have to lose 600,000 people before somebody says "We need something inexpensive, already in existence, & easier to get out there." Example: the rebirth of Vancomycin. Reply + camilo Colaco says: May 19, 2021 at 6:32 am aspirin, given coagulopathy? Reply * Claudio Romulo Siqueira Filho says: May 18, 2021 at 5:43 pm One of my students asked me why is it so difficult to make an effective vaccine for the novel coronavirus. My answer was: Imagine that I introduced to you five members of my family. Do you think that you can say that you really know my family? I'm saying this because a few years ago, I had many papers showing that a good vaccine product takes time to be "really well done." For Covid we had less than one year. I think we have a lot to learn about how long it takes to make a good vaccine against the Coronavirus family. Reply + Tim says: May 19, 2021 at 11:20 pm Cornavirus pandemics have been around since 2003 and there have been plenty of publications regarding it not necessarily in the US. Reply * Gwen G. says: May 18, 2021 at 10:12 pm I am immunocompromised. I have been on Prednisone every day for about 10 years for dx of lupus and RA. I have had both Moderna vaccine doses with the last being given 4/11/21. Additionally, I am a pancreatic cancer pt; Whipple 12/5/19 and last chemo 7/28/20 with regular scans for follow up. I got a sore arm after my first vaccine injection but no side effects with the second. Is there a test to see if I have antibodies for COVID 19? I feel I need to know this before I can relax into the new CDC guidelines. Thank you for your prompt reply in advance. Reply * Jean Bosco Sahaha says: May 20, 2021 at 5:12 am It sounds interesting. Reply * Gianni Zuccheri says: May 20, 2021 at 6:12 pm I would like to express a hypothesis starting from what is exposed in several articles. To simplify, I will mention : -- https://directorsblog.nih.gov/2021/05/18/ human-antibodies-target-many-parts-of-coronavirus-spike-protein/ -- The article https://directorsblog.nih.gov/2021/05/06/ "Dynamic View of Spike Protein Reveals Prime Targets for COVID-19 Treatments" reports: " ..They are sugar molecules called glycans that are thought to shield the spike protein by sweeping away antibodies. Also notice areas (purple) that the simulation identified as the most-attractive targets for antibodies, based on their apparent lack of protection by those glycans..." . . . Ozone is a strong oxidant. The spike protein is rich in cysteine residues, permanently oxidized by ozone. If the denaturation of viral structures occurs during treatment with Ozone therapy (it consists in the administration of a mixture of ozone and oxygen, called medical ozone, by autohemotherapy), their original conformation will be altered. The immune-system will face the viral structures, both in their original and altered conformation, thus producing two different lines of antibodies. I will use walnut as a comparison. Most often antibodies are produced (from vaccine or during illness) against what the shell represents. By means of ozone this shell is shattered and thus a content is exposed to which the antibody production would no longer be forced to chase the enemy's changes. Therefore, it does not matter if the shell changes, the kernel is unchanged and finally we can have some fixed points, both in the development of monoclonal therapies and in the study of vaccines. It would also be interesting to assess whether there is a different rate of reinfection between O3-treated patients and those who are not. Reply Leave a Comment Cancel reply Recent Items * Giving Thanks to Everyone at NIH's COVID-19 Vaccine Clinic May 20, 2021 * Understanding Neuronal Diversity in the Spinal Cord May 20, 2021 * Senators Visit NIH May 18, 2021 * Human Antibodies Target Many Parts of Coronavirus Spike Protein May 18, 2021 * Take Your Child to (Tele)Work Day May 17, 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 It takes every one of us doing our part to defeat #COVID19. 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