New Vaccination Strategy Developed That Could Prevent Future Coronavirus Outbreaks

Researchers in Japan have developed a vaccination strategy in mice that promotes the production of antibodies that can neutralize not only SARS-CoV-2, but also a wide variety of other coronaviruses. If the approach, published today (Oct. 8, 2021) in the Journal of Experimental Medicine, is successfully translated to humans, it could lead to the development of a next-generation vaccine that could prevent future coronavirus pandemics.

The SARS-CoV-2 virus responsible for COVID-19 enters human cells by using its spike protein to bind to a cell surface receptor called ACE2. The spike protein’s receptor-binding domain consists of two parts: a “core” region that is very similar to all coronaviruses, and a more specialized “head” region that mediates binding to ACE2.

Antibodies that recognize the main region of the spike receptor binding domain can block SARS-CoV-2 entry into cells, but offer little protection against other coronaviruses, such as the SARS-CoV-1 virus responsible for the outbreak of the virus. severe acute respiratory syndrome of 2002. In contrast, antibodies recognizing the core region of the spike receptor binding domain can prevent the entry of various coronaviruses into human cells. Unfortunately, individuals exposed to the viral spike protein tend to produce many antibodies to the core region, but few, if any, antibodies that recognize the core region.

The SARS-CoV-2 spike protein allows the virus to enter cells because its receptor-binding domain — consisting of a main region (red) and a core region (blue) — binds to the human ACE2 protein (grey). Credit: © 2021 Shinnakasu et al. Originally published in Journal of Experimental Medicine. DOI: 10.1084/jem.20211003

“This suggests that while the generation of broadly neutralizing antibodies is possible, SARS-CoV-2 infection and current vaccines are unlikely to protect against the emergence of new SARS-related viruses,” explains Professor Tomohiro Kurosaki of the WPI Immunology Frontier. Research out. Center at the University of Osaka in Japan. “As previous coronavirus epidemics such as SARS-CoV-1 and MERS-CoV have occurred due to zoonotic coronaviruses crossing the species barrier, the potential for the emergence of similar viruses in the future poses a significant threat to global public health, even in the face of effective vaccines for current viruses.”

Kurosaki and colleagues decided to test a new vaccination strategy that could enable the immune system to produce broader neutralizing antibodies. The researchers genetically engineered the receptor-binding domain of the SARS-CoV-2 spike protein and covered the head region with additional sugar molecules. These sugar molecules could protect the main region from the immune system and stimulate the production of antibodies against the unprotected core region of the receptor binding domain.

Indeed, mice immunized with these engineered proteins produced a much higher proportion of antibodies that recognized 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.

Much work will need to be done to translate this strategy to humans, but, Kurosaki says, “our data suggest engineered versions of the spike receptor binding domain could be a useful component for the development of next-generation generically protective vaccines.” prevent future coronavirus pandemics.”

Reference: “Glycan engineering of the SARS-CoV-2 receptor binding domain elicits cross-neutralizing antibodies to SARS-related viruses” Oct 8, 2021, Journal of Experimental Medicine.
DOI: 10.1084/jem.20211003