Research has opened a new door toward vaccine approaches and strategies against SARS viruses.
Scripps Research scientists discovered antibodies that induce broad immunity against SARS viruses, including emerging variants. SARS-CoV-2 is the virus that causes COVID, and mutates so rapidly that controlling it with vaccines is a challenge.
Antibodies effective against many different variants of SARS-CoV-2 were identified by Scripps Research scientists. The antibodies, according to a press release, would be effective against other SARS viruses including SARS-CoV-1, the highly lethal virus that caused an outbreak in 2003.
Research results, published Wednesday in Science Translational Medicine, concluded that certain animals make “pan-SARS virus” antibodies more so than humans, which gives scientists clues as to how to make better vaccines. Scientists found “these neutralizing antibodies recognize a viral spike region that is relatively more conserved, meaning that it is present across many different SARS viruses and is therefore less likely to mutate over time.” The research will enable development of next-generation vaccines with 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,” senior author Raiees Andrabi, PhD, an investigator in the Department of Immunology and Microbiology, said in the press release.
The study observed the immunization with the SARS-CoV-2 spike protein, the portion of the virus that penetrates and infects host cells, in rhesus macaque monkeys. According to the press release, two shots were administered, resembling a similar strategy used with currently available mRNA vaccines in humans. However, the macaques had a broad neutralizing antibody response against the virus, including variants such as Omicron.
The scientists collaborated with Ian Wilson’s lab at Scripps Research to further investigate the antibody structures, and found “the antibodies recognize a conserved region on the edge of the site where the spike protein binds to host cells, called the angiotensin converting enzyme 2 (ACE2) receptor binding site. This is different than the region where the majority of human antibodies target, which overlaps more with the ACE2 receptor binding site and is more variable to change.”
“The antibody structures reveal an important area common to multiple SARS-related viruses,” co-senior author Ian Wilson, DPhil, Hansen Professor of Structural Biology and Chair of the Department of Integrative Structural and Computational Biology, said in the press release. “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 press release stated that the macaque’s gene coding for these broad neutralizing antibodies is not the same in humans. The dominant immune response in humans is related to the macaque’s gene.
“According to our study, the macaques have an antibody gene that offers them more protection against SARS viruses,” Dennis Burton, PhD, co-senior author and chair of the Department of Immunology and Microbiology, said in the press release. “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.”
The study, “Broadly neutralizing antibodies to SARS-related viruses can be readily induced in rhesus macaques,” provides a door into the future of vaccinations for humans, but more investigation is needed to identify strategies against SARS viruses.
Scripps Research is an independent, nonprofit biomedical institute, and trains the next generation of leading scientists at our Skaggs Graduate School. Teams at Scripps Research Translational Institute harness genomics, digital medicine and cutting-edge informatics to understand individual health and render more effective healthcare.
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Rebecca Barnabi
