The spillovers of β-coronaviruses in humans and the emergence of SARS-CoV-2 variants highlight the need for broad coronavirus countermeasures.
A study co-authored by Dr. Jun Siong Low, Postdoc at the Cellular Immunology lab directed by Prof. Federica Sallusto at IRB (Institute for Research in Biomedicine, affiliated to USI) and published in Science on 05.08.2021 describes the structure and the activity of specific antibodies against all β-coronaviruses. This project was made possible thanks to a collaboration between the IRB, Humabs BioMed (a subsidiary of Vir Biotechnology), and the University of Washington.
In this study, the researchers described five monoclonal antibodies, three of which were isolated at the IRB, that can neutralize broadly across the β-coronaviruses genus.
Through structural analysis, they found that all five antibodies target the same site of the Spike glycoprotein (specifically the stem helix region of the more conserved S2 subunit). These antibodies exert their neutralizing capacity by inhibiting the fusion machinery required for viral entry.
One of these antibodies, S2P6, discovered at Humabs, was shown to exhibit effector functions and reduced viral burden in a preclinical model of SARS-CoV-2 infection.
Although these antibodies are usually rare, and their vast majority is of narrow specificities, the ones described in this study display broad activity against β-coronavirus with a high affinity.
“Our goal was to identify antibodies that could target and neutralize all β-coronaviruses. Such discoveries will allow us to use broadly neutralizing antibodies as potential therapeutics and identify the target epitope(s) of such antibodies to inform the design of a pan coronavirus vaccine, a single vaccine against all variants of β-coronavirus, which will be essential for pandemic preparedness” said Dr. Jun Siong Low.
Broad betacoronavirus neutralization by a stem helix-specific human antibody.
Pinto D., Sauer M. M., Czudnochowski N., Low J. S., Tortorici M. A., Housley M. P., Noack J., Walls A. C., Bowen J. E., Guarino B., Rosen L. E., di Iulio J., Jerak J., Kaiser H., Islam S., Jaconi S., Sprugasci N., Culap K., Abdelnabi R., Foo C., Coelmont L., Bartha I., Bianchi S., Silacci-Fregni C., Bassi J., Marzi R., Vetti E., Cassotta A., Ceschi A., Ferrari P., Cippa P. E., Giannini O., Ceruti S., Garzoni C., Riva A., Benigni F., Cameroni E., Piccoli L., Pizzuto M. S., Smithey M., Hong D., Telenti A., Lempp F. A., Neyts J., Havenar-Daughton C., Lanzavecchia A., Sallusto F., Snell G., Virgin H. W., Beltramello M., Corti D. and Veesler D.
Science 2021: DOI: 10.1126/science.abj3321