Antibodies that recognize the head area of the spike receptor-binding domain can block the entry of SARS-CoV-2 into cells but use little security versus other coronaviruses, such as the SARS-CoV-1 virus responsible for the extreme acute respiratory syndrome outbreak of 2002. Antibodies that recognize the core region of the spike receptor-binding domain, in contrast, can prevent the entry of numerous coronaviruses into human cells. However, individuals exposed to the viral spike protein tend to produce lots of antibodies against the head region but couple of, if any, antibodies that acknowledge the core area.
Researchers in Japan have established a vaccination method in mice that promotes the production of antibodies that can reduce the effects of not just SARS-CoV-2 however a broad variety of other coronaviruses. If successfully equated to human beings, the technique, to be published today (October 8, 2021), in the Journal of Experimental Medicine, could lead to the advancement of a next-generation vaccine capable of avoiding future coronavirus pandemics.
The SARS-CoV-2 virus accountable for COVID-19 goes into human cells by utilizing its spike protein to bind to a cell surface receptor called ACE2. The receptor-binding domain of the spike protein consists of two parts: a “core” area that is extremely comparable in all coronaviruses, and a more specific “head” region that mediates binding to ACE2.
Antibodies that recognize the head area of the spike receptor-binding domain can block the entry of SARS-CoV-2 into cells however use little protection versus other coronaviruses, such as the SARS-CoV-1 virus accountable for the serious intense breathing syndrome outbreak of 2002. Antibodies that recognize the core region of the spike receptor-binding domain, on the other hand, can avoid the entry of different coronaviruses into human cells. Sadly, nevertheless, individuals exposed to the viral spike protein tend to produce lots of antibodies versus the head region but couple of, if any, antibodies that acknowledge the core region.
The SARS-CoV-2 spike protein drives the viruss entry into cells because its receptor-binding domain– consisting of a head region (red) and a core region (blue)– binds to the human ACE2 protein (gray). Credit: © 2021 Shinnakasu et al. Initially published in Journal of Experimental Medicine. DOI: 10.1084/ jem.20211003.
” This suggests that, although the generation of broadly neutralizing antibodies is possible, SARS-CoV-2 infection and present vaccines are unlikely to offer defense versus the emergence of unique SARS-related viruses,” explains Professor Tomohiro Kurosaki from the WPI Immunology Frontier Research Center at Osaka University in Japan. “Given that prior coronavirus epidemics such as SARS-CoV-1 and MERS-CoV have actually occurred due to zoonotic coronaviruses crossing the types barrier, the capacity for the emergence of comparable viruses in the future presents a substantial hazard to worldwide public health, even in the face of reliable vaccines for current viruses.”.
Kurosaki and coworkers decided to test a new vaccination strategy that might make it possible for the immune system to produce more broadly neutralizing antibodies. The researchers genetically engineered the receptor-binding domain of the SARS-CoV-2 spike protein, covering its head area in extra sugar molecules. These sugar molecules could shield the head area from the body immune system and boost the production of antibodies versus the unshielded core area of the receptor-binding domain.
Mice vaccinated with these crafted proteins produced a much greater proportion of antibodies recognizing the core area of the spike protein receptor-binding domain. These antibodies were able to neutralize the cellular entry of not just SARS-CoV-2 however also SARS-CoV-1 and 3 SARS-like coronaviruses from bats and pangolins.
Much work will require to be done to translate this strategy to humans, but, states Kurosaki, “our data recommend that engineered versions of the spike receptor-binding domain could be a beneficial component for the advancement of broadly protective, next-generation vaccines to prevent future coronavirus pandemics.”.
Reference: “Glycan engineering of the SARS-CoV-2 receptor-binding domain generates cross-neutralizing antibodies for SARS-related viruses” 8 October 2021, Journal of Experimental Medicine.DOI: 10.1084/ jem.20211003.
