Please could you introduce yourself, tell us about your background in immunology, and what inspired your latest research into the ongoing COVID-19 pandemic?
After I got my Ph.D., I trained in fundamental immunology, particularly in the IgG receptor field. Then, I became independent, continuously pursuing B cell biology, and in the last ten years, I have focused on memory B cell biology.
Because the fundamental job of memory B cells is to induce protection against secondary re-infection of pathogens, I am very much interested in the development of next-generation of vaccines for COVID-19.
The virus responsible for the current pandemic is SARS-CoV-2 but other coronaviruses have emerged previously. How is the SARS-CoV-2 virus similar to that of SARS-CoV the virus responsible for the outbreak in 2002?
In regard to the RBD domain in S protein, about overall 75 % homology exists between these two viruses.
Image Credit: Darryl Fonseka/Shutterstock.com
There are two regions involved in the receptor-binding domain of the spike protein in SARS-CoV-2; a “head” region and a “core” region. How do the antibodies produced for these different regions vary?
Usually, people made more anti-head antibodies (Abs) (therefore, we call the head domain as immune-dominant), and less anti-core Abs (we call immune-subdominant).
What problems do these different antibodies have in terms of the current COVID-19 vaccines that have been developed?
In contrast to the existence of structural diversity of the head-domain between SARS-CoV-2 and SARS-related viruses, structures of the core-domain are well conserved among various SARS-related viruses. Hence, if we can make sufficient amounts of high-quality neutralizing Abs against the core domain, we can protect from not only SARS-CoV-2 infection but also from SARS-related viruses.
However, as I mentioned above, people made dominantly Abs against the head, but not core-domain. Thus, in order to focus Abs towards the core-domain, we should suppress the immune-dominancy on the head-domain. Otherwise, we cannot make sufficient Abs against the core domain.
Prior epidemics have occurred due to zoonotic coronaviruses jumping species barriers. Despite us having an effective vaccine for the current coronavirus (SARS-CoV-2), why is there still a significant threat to global public health?
The current COVID-19 vaccine is effective for SARS-CoV-2, but not for other SARS-related viruses (for example, SARS-CoV, WIV1).
How did you carry out your latest research that investigated a new vaccination strategy? What did you discover?
We are thinking and thinking about 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.
We tried two ways; targeted point mutation and deletion of proteins; glycan-engineering. The latter works fine.
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How could your research be replicated and used to develop a next-generation vaccine that is capable of not only neutralizing SARS-CoV-2 but other coronaviruses as well? What further research needs to be carried out before this can be successfully translated to humans?
Because Abs against the core-domain of the RBD is so similar among different SARS-related viruses, they can cross-protect.
Obviously, we should test whether our approach also works in the human immune system.
What are the next steps for you and your research?
By using SARS-CoV-2-infected patients and vaccinated persons, we can try to identify the most high-quality broadly neutralizing monoclonal Abs recognizing the core-subdomain of RBD.
Then, we will design the engineered antigens which specifically induce such bn Abs.
Where can readers find more information?
About Professor Tomohiro Kurosaki
1987 Received Ph.D. from Kyoto University.
1988 Postdoctoral Fellow at the Sloan-Kettering Institute.
1992 Senior Research Scientist at Lederle Laboratories.
1996 Professor at Kansai Medical University.
2001 Group Director at RIKEN.
2008 Specially Appointed Professor at WPI Immunology Frontier Research Center, Osaka University.
2021 Adjunct Professor at Center for Infectious Diseases Education and Research (CiDER), Osaka University.
Professor Kurosaki is currently supervising two laboratories.
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