COVID-19 Patient Antibodies Point Researchers Toward Broad Coronavirus Vaccines

Pictured is the conserved SARS-CoV-2 spike receptor binding site for broad vaccine targeting. Courtesy of Meng Yuan

Scientists at Scripps Research have characterized 30 antibodies that recognize a wide range of coronaviruses—successfully blocking not only all the SARS-CoV-2 variants that were tested, but other, related viruses including SARS-CoV-1, which caused the original SARS outbreak with high mortality in 2003, one found only in bats and another from pangolins. The antibodies were all isolated from people with “hybrid immunity” who had been infected with SARS-CoV-2 and subsequently vaccinated against the virus.

The new details on the antibodies, published today in Nature Immunology, are a step toward the next generation of coronavirus vaccines, which may help ward off a broader swath of viruses than the current vaccines specific to SARS-CoV-2.

“It’s very encouraging that despite SARS-CoV-2 mutating, there are still parts of the virus you can target for broad vaccination strategies,” says senior author Raiees Andrabi, PhD, an investigator in the Department of Immunology and Microbiology.

At the same time researchers work to develop new treatments and vaccines for the ongoing COVID-19 pandemic, many are also hoping to prevent the next pandemic. Coronaviruses—a broad group of viruses which also cause some common colds—have been responsible for COVID-19 as well as previous outbreaks caused by SARS-CoV-1 and Middle East Respiratory Syndrome (MERS) virus. A vaccine that helps the immune system recognize not only many SARS-CoV-2 variants, but other SARS-causing coronaviruses, could stop these viruses from spreading throughout the population.

In the new study, Andrabi and his colleagues compared antibody responses elicited in 21 people who had recovered from COVID-19, 10 people who had been vaccinated against COVID-19, and 15 with hybrid immunity from both. People with hybrid immunity showed the strongest and broadest spectrum of antibodies, able to neutralize—or block—five variants of SARS-CoV-2 (Alpha, Beta, Gamma, Delta and Omicron), SARS-CoV-1, as well as a pangolin coronavirus and one from horseshoe bats in China. No antibodies from the vaccination-only or infection-only group could neutralize all the viruses.

The team isolated 107 antibodies from two hybrid immunity donors, screening for molecules that could bind to both SARS-CoV-1 and SARS-CoV-2 spike proteins. Then, they homed in on 30 of those antibodies, many of which also neutralized the bat and pangolin coronaviruses for a closer look.

Most of those 30 antibodies, they found, recognized the same part of the viruses’ structures, called the receptor-binding domain on the spike protein. Certain segments of the receptor-binding domain, the finding suggested, were not changing as different coronaviruses evolved. The 30 antibodies also had similarities when it came to how they were produced by the body, an important clue for researchers in how to design vaccines that prompt the immune system to produce the same antibodies.

To show that the antibodies did not just bind to the viruses in the lab, but could actually impact the immune system’s ability to fight each pathogen, Andrabi’s group, in collaboration with co-senior authors Ralph Baric and Lisa Gralinski at the University of North Carolina at Chapel Hill, observed what happened when mice treated with three of the most potent antibodies—known as CC25.36, CC25.53 and CC25.54—were exposed to SARS-CoV-2, SARS-CoV-1, or the horseshoe bat virus SHC014-CoV. For all three viruses, the mice that had been treated with the antibodies had significantly lower levels of virus in their lungs compared to control mice.

“We saw amazing protection against these three viruses,” says Andrabi. “That tells us that if we are able to induce these antibodies by vaccination, they will likely give you broad protection against diverse SARS-like viruses.”

“Now that we know these antibodies work, the next goal is to design vaccines and to try to elicit similar broadly-neutralizing antibodies by vaccination in approaches that have been pioneered at Scripps Research for HIV,” says Dennis Burton, PhD, co-senior-author and chair of the Department of Immunology and Microbiology.

In addition to Andrabi, authors of the study, “Targeted isolation of diverse human protective broadly neutralizing antibodies against SARS-like viruses,” include Wan-ting He, Rami Musharrafieh, Ge Song, Katharina Dueker, Sean Callaghan, Peter Yong, Nathan Beutler, Jonathan Torres, Reid Volk, Panpan Zhou, Meng Yuan, Hejun Liu, Fabio Anzanello, Tazio Capozzola, Mara Parren, Elijah Garcia, Ian Wilson, Andrew Ward, Thomas Rogers, and Dennis Burton of Scripps Research; Long Ping Tse, David Martinez, Alexandra Schafer, Ralph Baric and Lisa Gralinski of the University of North Carolina at Chapel Hill; Stephen Rawlings and Davey Smith of University of California, San Diego; and Yana Safanova of Johns Hopkins University.