Prof Tomohiro Kurosaki (WPI Immunology Frontier Research Center, Osaka University), and his team have developed a vaccination strategy in mice that promotes the production of antibodies that can neutralize not only SARS-CoV-2 but a broad range of other coronaviruses as well.
If successfully translated to humans, the approach, could lead to the development of a next-generation vaccine capable of preventing future coronavirus pandemics.
The Covid virus enters the human cells by using 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” region that is very similar in all coronaviruses, and a more specialized “head” region that mediates binding to ACE2.
Generally people make more anti-head antibodies (Abs), (therefore, we call the head domain as immune-dominant), and less anti-core Abs (we call immune-subdominant).
Antibodies that recognize the head region of the spike receptor-binding domain can block the entry of SARS-CoV-2 into cells but offer little protection against other coronaviruses, such as the SARS-CoV-1 virus of 2002. Antibodies that recognize the core region of the spike receptor-binding domain, in contrast, can prevent the entry of various coronaviruses into human cells. Unfortunately, however, individuals exposed to the viral spike protein tend to produce lots of antibodies against the head region but few, if any, antibodies that recognize the core region.
Prof Kurosaki is developing a way on how to suppress the immune-dominancy on the head-subdomain, thereby skewing the Ab response to the immune-subdominant core –domain, because of the structural similarity to the core-domain among the SARS-related viruses is very high.
He has tried two possible ways - targeted point mutation and deletion of proteins; glycan-engineering. The latter works fine.
This new vaccination strategy that might enable 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 region in additional sugar molecules. These sugar molecules could shield the head region from the immune system and boost the production of antibodies against the unshielded core region of the receptor-binding domain.
Mice immunized with these engineered proteins produced a much higher proportion of antibodies recognizing the core region of the spike protein receptor-binding domain. These antibodies were able to neutralize the cellular entry of not only SARS-CoV-2 but also SARS-CoV-1 and three SARS-like coronaviruses from bats and pangolins.
A lot more work has to go into adapt this into human use but the team is quite hopeful that this could be done.
http://www.ifrec.osaka-u.ac.jp/en/laboratory/tomohiro_kurosaki
If successfully translated to humans, the approach, could lead to the development of a next-generation vaccine capable of preventing future coronavirus pandemics.
The Covid virus enters the human cells by using 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” region that is very similar in all coronaviruses, and a more specialized “head” region that mediates binding to ACE2.
Generally people make more anti-head antibodies (Abs), (therefore, we call the head domain as immune-dominant), and less anti-core Abs (we call immune-subdominant).
Antibodies that recognize the head region of the spike receptor-binding domain can block the entry of SARS-CoV-2 into cells but offer little protection against other coronaviruses, such as the SARS-CoV-1 virus of 2002. Antibodies that recognize the core region of the spike receptor-binding domain, in contrast, can prevent the entry of various coronaviruses into human cells. Unfortunately, however, individuals exposed to the viral spike protein tend to produce lots of antibodies against the head region but few, if any, antibodies that recognize the core region.
Prof Kurosaki is developing a way on how to suppress the immune-dominancy on the head-subdomain, thereby skewing the Ab response to the immune-subdominant core –domain, because of the structural similarity to the core-domain among the SARS-related viruses is very high.
He has tried two possible ways - targeted point mutation and deletion of proteins; glycan-engineering. The latter works fine.
This new vaccination strategy that might enable 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 region in additional sugar molecules. These sugar molecules could shield the head region from the immune system and boost the production of antibodies against the unshielded core region of the receptor-binding domain.
Mice immunized with these engineered proteins produced a much higher proportion of antibodies recognizing the core region of the spike protein receptor-binding domain. These antibodies were able to neutralize the cellular entry of not only SARS-CoV-2 but also SARS-CoV-1 and three SARS-like coronaviruses from bats and pangolins.
A lot more work has to go into adapt this into human use but the team is quite hopeful that this could be done.
http://www.ifrec.osaka-u.ac.jp/en/laboratory/tomohiro_kurosaki
