NIH Support: National Institute of Allergy and Infectious Diseases National Cancer Institute National Institute of General Medical Sciences National Center for Advancing Translational Sciences Gregory Ippolito (University of Texas at Austin) 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. Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes. 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. 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. 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. 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. 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.Īlso noteworthy, about 40 percent of the circulating antibodies target yet another portion of the spike called the S2 subunit. 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. They also prevented a lethal mouse-adapted version of the coronavirus from infecting mice. 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).įurther study in cell culture showed that NTD-directed antibodies do indeed neutralize the virus. It involves production of antibodies capable of covering areas across the entire spike. This suggests a successful immune response doesn’t concentrate on the RBD. 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. 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. The new study, led by Gregory Ippolito and Jason Lavinder, The University of Texas at Austin, took a different approach. 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 RBD is the portion of the spike that attaches directly to human cells. 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. This picture suggests that an effective neutralizing immune response targets a wider swath of the virus’ now-infamous spike protein than previously recognized. 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.Īn 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. But these individuals’ immune systems still hold onto enduring clues about how best to neutralize SARS-CoV-2, the coronavirus that causes COVID-19. Credit: University of Texas at Austinįor many people who’ve had COVID-19, the infections were thankfully mild and relatively brief. Francis Collins Caption: 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). Human Antibodies Target Many Parts of Coronavirus Spike Protein
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