New Research Finds Good News for Designing the Next Generation of Coronaviruses Vaccines

An analysis of blood plasma samples from four people who recovered from SARS-CoV-2 infections shows that most of the antibodies circulating in the blood – about 84% on average – target areas of the viral spike protein outside the receptor binding domain ( RBD). Credit: University of Texas at Austin

Our immune systems cover the SARS-CoV-2 Spike protein with antibodies

The most complete picture to date shows how antibodies produced in humans that effectively fight SARS-CoV-2 work to neutralize the portion of the virus responsible for causing infection. In the journal Science, researchers at the University of Texas at Austin describe the finding, which is good news for designing next-generation vaccines to protect against variants of the virus or future emerging coronaviruses.

Previous research focused on one group of antibodies that target the most obvious part of the coronavirus spike protein called the receptor binding domain (RBD). Since the RBD is the portion of the peak that attaches directly to human cells and allows the virus to infect them, it was correctly believed to be a primary target of the immune system. But by testing blood plasma samples from four people who recovered from SARS-CoV-2 infections, the researchers found that most of the antibodies circulating in the blood – about 84% on average – target areas of the viral spike protein outside the RBD – and apparently for good reason.

“We found that these antibodies paint the entire spike, both the arch and the stem of the spike protein, which looks a bit like an umbrella,” said co-corresponding author Greg Ippolito, a research associate professor at UT Austin’s Department of Health. Molecular Biosciences and an assistant professor of oncology at the university’s Dell Medical School. “The immune system sees the entire peak and tries to neutralize it.”

Many of these non-RBD-targeting antibodies that the team identified act as a powerful weapon against the virus by targeting a region in part of the spike protein residing in what would be the umbrella’s canopy, the N -terminal domain (NTD). These antibodies neutralize the virus in cell cultures and have been found to prevent a lethal, mouse-modified version of the virus from infecting mice.

The NTD is also part of the viral spike protein that often mutates, especially in several variants of concern. This suggests that one reason these variants are so effective at evading our immune system is that they can mutate around one of the most common and powerful types of antibodies in our arsenal.

“There is an evolutionary arms race between the virus and our immune system,” said Jason Lavinder, research associate in the McKetta Department of Chemical Engineering and co-corresponding author of the new study. “We all develop a standard immune response to this virus, targeting this one spot and putting selective pressure on the virus. But then the virus also exerts its evolutionary power by trying to change our selective immune pressure. “

Despite these maneuvers through SARS-CoV-2, the researchers said that about 40% of the circulating antibodies target the stem of the spike protein called the S2 subunit, which is also a component that the virus does not seem to read easily. can change.

“That’s reassuring,” said Ippolito. “That is an advantage that our immune system has. It also means that our current vaccines raise antibodies that target that S2 subunit, which are likely to provide a new layer of protection against the virus. “

That’s also good news for designing next-generation vaccine boosters or vaccines against variants of concern, and even developing a vaccine that can protect against future pandemics of other strains of the coronavirus.

“It means we have a strong rationale for developing the next generation of SARS-CoV-2 vaccines or even a pan-coronavirus vaccine targeting any strain,” said Ippolito.

UT Austin researchers are among the many researchers in the world who are now pursuing the development of a single coronavirus vaccine to combat infection of all coronaviruses, not just SARS-CoV-2.

Reference: “Prevalent, Protective, and Convergent IgG Recognition of SARS-CoV-2 Non-RBD Spike Epitopes” by William N. Voss, Yixuan J. Hou, Nicole V. Johnson, George Delidakis, Jin Eyun Kim, Kamyab Javanmardi , Andrew P. Horton, Foteini Bartzoka, Chelsea J. Paresi, Yuri Tanno, Chia-Wei Chou, Shawn A. Abbasi, Whitney Pickens, Katia George, Daniel R. Boutz, Dalton M. Towers, Jonathan R. McDaniel, Daniel Billick , Jule Goike, Lori Rowe, Dhwani Batra, Jan Pohl, Justin Lee, Shivaprakash Gangappa, Suryaprakash Sambhara, Michelle Gadush, Nianshuang Wang, Maria D. Person, Brent L. Iverson, Jimmy D. Gollihar, John Dye, Andrew Herbert, Ilya J. Finkelstein, Ralph S. Baric, Jason S. McLellan, George Georgiou, Jason J. Lavinder, and Gregory C. Ippolito, May 4, 2021, Science.
DOI: 10.1126 / science.abg5268

The study’s lead author is William Voss, a graduate student at UT Austin. In addition to Lavinder and Ippolito, UT Austin’s senior authors are Jimmy Gollihar, Ilya Finkelstein, Brent Iverson, Jason McLellan, and George Georgiou. Georgiou and Ippolito are also affiliated with UT Austin’s Dell Medical School. Gollihar is also affiliated with the South Army Research Laboratory.

Collaborating institutions include the University of North Carolina at Chapel Hill, the US Army Medical Research Institute of Infectious Diseases, and the Centers for Disease Control and Prevention.

This research was funded in part by the National Institutes of Health, the Clayton Foundation, and the Welch Foundation.