Creating a Cross-protective Coronavirus Vaccine

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Researchers have found that by targeting the core region of the spike protein receptor-binding domain, which remains structurally similar among SARS-related viruses, they can create a vaccine that offers cross-protection against SARS coronaviruses.

The COVID pandemic, caused by the β-coronavirus SARS-CoV-2, alerted the world to the seriousness of the threat posed by novel viruses. To protect against similar future outbreaks, there is an urgent need for broadly protective vaccines against SARS-related coronaviruses. In a recent study published in Journal of Experimental Medicine, a team of researchers led by Osaka University generated an immune antigen that was based on a conserved protein on the surface of SARS-related viruses. In mice immunised with this antigen, cross-neutralising antibodies against SARS-related viruses were elicited.

The coronavirus spike protein, specifically the receptor-binding domain (RBD) of spike protein that enables the virus to attach to host cells is a target for the development of neutralising antibodies, and a promising vaccine candidate. The RBD is made of two regions: the head, which is more immune-reactive and so has the most antibodies created for it, and the core. The head however changes more rapidly, while the core region is more stable amongst SARS-related viruses. Antibodies raised against this conserved core region of the RBD can therefore generate cross-protection against multiple SARS-related viruses.

As lead authors Ryo Shinnakasu and Shuhei Sakakibara explained, “The key to generating a vaccine that offers broad cross-protection among related viruses is to target a structure on the viral surface that is highly conserved. Our approach was to generate a vaccine in which the non-conserved region was masked from the immune system by the introduction of a carbohydrate molecule (or glycan) by a method known as glycan engineering. This would in turn expose the conserved core region of the RBD of spike protein.” When used to immunise mice, protective antibodies were induced that recognised the RBD core region not only of SARS-CoV-2 but also of other SARS-related viruses, such as bat SARS-like coronavirus, WIV1-CoV.

This finding is particularly promising because it demonstrates the potential for highly protective vaccines against various SARS-related viruses. As senior author Tomohiro Kurosaki warned, “Despite the existence of effective vaccines against current viruses, there is potential for the emergence of similar viruses in the future. This highlights the real need for broadly protective vaccines against SARS-related coronaviruses.”

The novel approach of vaccine design that they describe may help protect against a future global health crisis such as that experienced during the COVID pandemic.

Source: Osaka University

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