Recently published in Science, a study led by the Sallusto Laboratory (ETH Zurich and IRB-USI, Bellinzona) and the Veesler Laboratory (University of Washington, Seattle) describes a new class of antibodies that bind to and neutralize most human and animal coronaviruses, including all SARS-CoV-2 variants. These antibodies reveal a new target for the design of universal coronavirus vaccines.
Coronaviruses have been circulating within the human population for decades and seasonally cause common colds. However, multiple recent zoonotic transmission (from animals) have led to the introduction of highly pathogenic SARS-CoV, MERS-CoV and SARS-CoV-2 that have caused epidemics and the current pandemic. In view of the global impact of the current pandemic and the likely occurrence of new zoonotic transmission, there is an urgent need to develop a “universal” vaccination strategy that can offer broad protection against all coronaviruses.
One important component in immunity is antibodies, “Y”-shaped proteins that are produced by B cells of our immune system following infection or vaccination. Antibodies can bind to viruses preventing infection of host cells but are usually highly specific for a given species of virus. In this study, the team searched for a rare class of antibodies that would recognize and neutralize all coronavirus species.
Using an innovative and sensitive methodology, the team isolated a new class of antibodies from infected and vaccinated individuals that binds to and neutralizes most human and animal coronaviruses, including all SARS-CoV-2 variants. These antibodies bind to a region of the coronavirus spike protein called the fusion peptide, which is essential for viral entry into the host cell and is highly conserved among different coronaviruses. Using structural and functional approaches, the team found that the fusion peptide is kept ‘hidden’ in the spike protein and becomes exposed only when the virus spike protein binds to the receptor on the host cell.
This discovery of the fusion peptide as a target for broadly neutralizing antibodies paves the way for the design next generation vaccines capable of inducing such broadly protective antibodies.
This study was made possible through collaborative efforts with Humabs BioMed (subsidiary of Vir Biotechnology), clinical institutions from Switzerland and Italy: Ente Ospedaliero Cantonale (EOC), the Clinica Luganese Moncucco, INGM Milano, and University of Leuven.
Article
ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies
Jun Siong Low, Josipa Jerak, Alejandra Tortorici, Matthew McCallum, Dora Pinto, Antonino Cassotta, Mathilde Foglierini, Federico Mele, Rana Abdelnabi, Birgit Weynand, Julia Noack, Martin Montiel-Ruiz, Siro Bianchi, Fabio Benigni, Nicole Sprugasci, Anshu JoshiJohn E. Bowen, Cameron Stewart, Megi Rexhepaj, Alexandra C. Walls, David Jarrossay, Diego Morone, Philipp Paparoditis, Christian Garzoni, Paolo Ferrari, Alessandro Ceschi, Johan Neyts, Lisa A. Purcell, Gyorgy Snell, Davide Corti, Antonio Lanzavecchia, David Veesler and Federica Sallusto.
Science, 2022. DOI: 10.1126/science.abq2679
The team isolated a new class of antibodies that neutralize different coronaviruses by binding to the conserved fusion peptide of the spike protein.
