La Jolla researchers discover antibodies that offer broad immunity against SARS viruses, including variants

As the world has witnessed, SARS-CoV-2, the coronavirus that causes COVID-19, is difficult to control because of its ability to rapidly mutate and produce many different variants. But scientists at Scripps Research in La Jolla have identified antibodies that are effective against many different SARS-CoV-2 variants, as well as other SARS viruses like SARS-CoV-1, the lethal virus that caused an outbreak in 2003.

The results indicate that certain animals are surprisingly more able to make these types of “pan-SARS virus” antibodies than humans, giving scientists clues as to how to make better vaccines.

The findings, published Aug. 10 in Science Translational Medicine, reveal the antibody structures that produce the more comprehensive immune response. The researchers found that these neutralizing antibodies recognize a viral spike region that is present across many different SARS viruses and is therefore less likely to mutate over time. That discovery could help in developing next-generation vaccines that can offer additional protection against emerging SARS-CoV-2 variants and other SARS-related viruses.

“If we can design vaccines that elicit the similar broad responses that we’ve seen in this study, these treatments could enable broader protection against the virus and variants of concern,” said senior author Raiees Andrabi, an investigator in the Department of Immunology and Microbiology at Scripps Research.

In the study, rhesus macaque monkeys were immunized with the SARS-CoV-2 spike protein — the outside portion of the virus that enables it to penetrate and infect host cells. Two shots were administered, resembling a strategy used with currently available mRNA vaccines in humans. Unlike those vaccines, however, the macaques were shown to have a broad neutralizing antibody response against the virus, including variants such as Omicron.

Intrigued by the difference, the scientists collaborated with Ian Wilson’s lab at Scripps Research to investigate the antibody structures. They found the antibodies recognize a region on the edge of the site where the spike protein binds to host cells. This is different than the region that the majority of human antibodies target.

“The antibody structures reveal an important area common to multiple SARS-related viruses,” said co-senior author Wilson, a professor of structural biology and chairman of the Department of Integrative Structural and Computational Biology. “This region to date has rarely been seen to be targeted by human antibodies and suggests additional strategies that can be used to coax our immune system into recognizing this particular region of the virus.”

The scientists note that the macaque’s gene coding for the broad neutralizing antibodies — known as IGHV3-73 — is not the same in humans. The dominant immune response in humans is related to the IGHV3-53 gene, which produces a potent but much narrower neutralizing antibody response.

However, the researchers say their discovery opens the door to design and engineer vaccines that elicit more broad protection against SARS-CoV-2 and its many variants.

“According to our study, the macaques have an antibody gene that offers them more protection against SARS viruses,” said Dennis Burton, co-senior author and chairman of the Department of Immunology and Microbiology. “This observation teaches us that studying the effect of a vaccine in monkeys can only take us so far but also reveals a new target for our vaccine efforts that we might be able to exploit by advanced protein design strategies.”

Because the genetics differ, Andrabi says more investigation is needed, not only for identifying new strategies against SARS viruses but also for making sure scientists are using the best translational models for their research. ◆