Japanese researchers have developed a vaccination strategy in mice that promotes the antibody production capable of neutralizing not only the SARS-CoV-2, but also a wide range of other coronaviruses.
As published in the ‘Journal of Experimental Medicine’, if successfully transferred to humans, the method could lead to the development of a new generation vaccine capable of preventing future coronavirus pandemics.
The SARS-CoV-2 virus responsible for COVID-19 enters human cells using its spike protein to bind to a receptor on the cell surface called ACE2. The spike protein receptor-binding domain 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.
Antibodies that recognize the head region of the spike receptor-binding domain may block the entry of SARS-CoV-2 into cells, but offer little protection against other coronaviruses, such as the SARS-CoV-1 virus responsible for the virus. 2002 outbreak of severe acute respiratory syndrome.
In contrast, antibodies that recognize the central region of the spike receptor-binding domain can prevent the entry of various coronaviruses into human cells. Unfortunately, however, individuals exposed to the viral spike protein tend to produce many antibodies against the head region, but few, if any, that recognize the core region.
“This suggests that, although the generation of broadly neutralizing antibodies is possible, it is unlikely that SARS-CoV-2 infection and current vaccines provide protection against the emergence of new SARS-related viruses,” explains Professor Tomohiro. Kurosaki, from the WPI Immune Frontier Research Center at Osaka University, Japan.
“Since previous coronavirus epidemics such as SARS-CoV-1 and MERS-CoV have occurred due to zoonotic coronaviruses crossing the species barrier, the possibility of similar viruses emerging in the future poses a significant threat to the global public health, even in the face of effective vaccines for current viruses ”, he adds.
Kurosaki and his colleagues decided to test a new vaccination strategy that could allow the immune system to produce broader neutralizing antibodies. The researchers genetically modified the spike protein receptor-binding domain of SARS-CoV-2, coating its head region with additional sugar molecules. These sugar molecules could protect the head region of the immune system and enhance the production of antibodies against the unprotected core region of the receptor-binding domain.
In fact, mice immunized with these modified proteins produced a much higher proportion of antibodies that recognized the central region of the spike protein receptor-binding domain. These antibodies were able to neutralize the cellular entry not only of SARS-CoV-2 but also of SARS-CoV-1 and three SARS-like coronaviruses from bats and pangolins.
Much work will be needed to translate this strategy into humans, but according to Kurosaki, “these data suggest that modified versions of the spike receptor-binding domain could be a useful component for the development of broadly protective next-generation vaccines for prevent future coronavirus pandemics ”.