The Ighv3-73 gene has been identified in macaques, encoding wildcard antibodies capable of recognizing portions of the more conserved Spike protein. According to the authors, these are important steps in obtaining better vaccines
Scientists from the American Scripps Research Institute discovered in macaques “pan-coronavirus” antibodies “effective against many different variants of Sars-CoV-2”, but also “against other Sars viruses such as Sars-CoV-1, the highly lethal pathogen responsible for the 2003 epidemic”. The study, published in Science Translational Medicine, indicates that “some animals are surprisingly more capable of producing this type of anti-pan-Sars virus” than humans, “offering researchers” clues as to how to develop
“. “If we can design vaccines that elicit broad” immune “responses, similar to those seen” in the new work, “they could guarantee greater protection against the virus”.
“And the variants of concern,” says the senior author Raiees Andrabiresearcher in the Scripps Department of Immunology and Microbiology.
The “wildcard” antibodies identified in the study recognize a relatively more conserved portion of the viral Spike protein, which is present in many different Sars viruses and less prone to mutating over time. An element that the authors consider useful for the development of «next generation vaccines», which are «capable of offering additional protection against the emerging variants of Sars-CoV-2 and against other Sars viruses».
In the study, rhesus macaque monkeys were immunized with Sars-CoV-2’s Spike protein, the hook the virus uses to attach and infect target cells. They were administered two doses, according to a strategy similar to that adopted with mRna anti-Covid vaccines. Unlike what happens in humans after the administration of these products, it has been seen, however, that the macaques developed a ‘broad neutralizing antibody response against the virus, including variants such as Omicron. Intrigued by this clear difference, the scientists decided to investigate the structure of macaques’ super antibodies, discovering that they recognize a different Spike region than most human antibodies target: a more conserved area, in fact, located more laterally on the edge of the binding point between Spike and the Ace2 receptor of our cells. This is an “important area, common to several Sars viruses, and which so far has only rarely been the target of human antibodies”, highlights the study’s senior co-author. Ian Wilsonhead of the Scripps Department of Integrated Structural and Computational Biology, which suggests the opportunity to study “additional strategies to be exploited to persuade our immune system to recognize this particular region of the virus”.
The macaque gene that coding for these neutralizing super antibodies anti-Sars – the authors also remark – is Ighv3-73, different from the Ighv3-53 gene that regulates the human immune response, which is powerful, but with a much narrower spectrum. According to the researchers, understanding this could help design vaccines, or vaccine-adjuvant combinations, that induce broader protection against Sars-CoV-2 and its many variants. «From our study – comments the senior co-author Dennis Burtonat the head of the Scripps Department of Immunology and Microbiology – it emerges that macaques have an antibody gene that offers them greater protection against SARS viruses. This observation sets a new goal for our vaccine efforts, which we may be able to achieve using advanced protein design approaches. “
August 10, 2022 (change August 10, 2022 | 20:22)
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