Detail of public bnAbs and how they interact with SARS-CoV-2 (green helix) and MERS-CoV (orange helix)
Results from a Scripps Research and UNC team have pave the way for a vaccine and therapeutic antibodies that might be stockpiled in the event of future coronavirus epidemics.
Scientists from Scripps Research and UNC have discovered antibodies in the blood of some COVID-19 donors that can deter infection from a wide spectrum of coronaviruses—specifically, in individuals who have recovered from the virus and were then vaccinated. This includes not only the COVID-19-causing SARS-CoV-2, but also SARS-CoV-1 and MERS-CoV.
The researchers' detailed analysis of the antibodies and their virus binding sites, published on February 15, 2023, might lead to the development of a wide range of coronavirus vaccines and related antibody therapies. Both may be used against future coronavirus pandemics as well as any future versions of SARS-CoV-2.
Raiees Andrabi, PhD, a Scripps Research associate professor, says her research shows that individual human monoclonal antibodies can be found that protect against all three recently fatal coronaviruses, including SARS-CoV-1, SARS-CoV-2, and MERS-CoV.
Dennis Burton, PhD, professor and James and Jessie Minor Chair of the Department of Immunology and Microbiology, and Ian Wilson, PhD, Hansen Professor of Structural Biology and chair of the Department of Integrative Structural and Computational Biology were among the other Scripps Research co-senior authors.
SARS-CoV-2, along with SARS-CoV-1 (the cause of the 2002-04 SARS epidemic) and MERS-CoV (the cause of deadly Middle East Respiratory Syndrome), belong to a large group of coronaviruses called betacoronaviruses. These viruses mutate at a modestly high rate, creating a significant challenge for the development of new SARS-CoV-2 varieties that can spread even among vaccination recipients.
The Andrabi/Burton/Wilson labs have discovered a vulnerable site that does not mutate much in betacoronaviruses that infect a number of animal species. This site, which is in the S2 region (or base) of the viral spike protein, is relatively conserved on betacoronaviruses that infect a variety of animals.
The S2 site plays a key role in how betacoronaviruses progress from receptor binding to the membrane fusion that allows entry into host cells in the respiratory tract. This suggests that some human antibodies may be targeted to this site in order to provide long-term and widespread protection against betacoronaviruses.
These volunteers were individuals who had recovered from COVID-19 and then were vaccinated. Somewhat to the researchers' surprise, they discovered that antibodies to the vulnerable S2 site were present in the vast majority of people in the latter group—people who had recovered from COVID-19 and then were vaccinated—but at a much lower frequency in the others.
Researchers found that several of these antibodies, not only against SARS-CoV-2, but also against SARS-CoV-1 and MERS-CoV betacoronaviruses, were effective in lab virus neutralization experiments and virus-challenge experiments with mice at UNC.
Burton believes that a vaccination strategy that can induce such antibodies is likely to provide broad protection against a wide range of betacoronaviruses.
Several antibodies that were bound to S2 were studied in structural detail, revealing their common binding sites and modes of binding, providing important information that may assist in the development of future vaccinations targeting this region.
Wilson believes that "stricted rational vaccine strategies" could utilize this molecular evidence of antibody interactions with the S2 domain to design pan-betacoronavirus vaccinations.
The researchers have already applied their findings to the initial design and testing of a feasible "pan-betacoronavirus" vaccine candidate, which might be stored to avoid future epidemics. Potentially, a therapeutic blend of different S2-targeting antibodies, perhaps as a cocktail with antibodies to other spike regions, might be utilized to prevent infection by a novel betacoronavirus or to prevent disease in individuals already infected.
Panpan Zhou, Ge Song, Meng Yuan, Alexandra Schäfer, Fabio Anzanello, Peter Yong, Linghang Peng, Katharina Dueker, Elijah Garcia, Stephen A. Rawlings, Davey M. Smith, David Nemazee, Yana Safonova, Ian A. Wilson, Ralph S. Baric, Lisa E. Gralinski, Dennis R. Burton, and Raiees Andrabi, 15 February 2023, Immunity
Panpan Zhou, Ge Song, Hejun Liu, Longping Tse, Alexandra Schäfer, Fabio Anzanello, Peter Yong, Linghang Peng, Katharina Dueker, Elijah Garcia, Stephen Rawlings, David Nemazee, Joseph Jardine, Yana Safonova, Thomas Rogers, Ian Wilson, Lisa Gralinski, Dennis Burton, and Raiees Andrabi.
The National Institutes of Health (UM1 AI44462, AI036214, 5T32AI007384, U54 CA260543, AI157155, R21 AI145372), the Bill and Melinda Gates Foundation (INV-004923), and the James B. Pendleton Charitable Trust (JB-004923).
