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Engineering Immunogens for Vaccine Design

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The human respiratory syncytial virus (RSV) is one of the last early childhood viruses for which there is no vaccination. While most adults infected with RSV exhibit only cold-like symptoms, the virus is responsible for approximately 200,000 deaths per year in children under five. CSSB Associate Member Prof. Dr. Thomas Krey from the University of Lübeck was involved in a recent study which demonstrates that immunogens can be engineered to induce RSV-neutralizing antibodies. The publication which appeared in Science is an important step towards the development of a vaccine for RSV and the result of a long standing collaboration between Krey and Prof. Dr. Bruno Correia from EPFL in Lausanne.

Neutralizing antibodies, as their name indicates, disarm infectious pathogens. These antibodies are known to bind to specific epitopes – the part of a pathogen’s immunogen that is recognized by the immune system.  Using a novel computational design strategy called TopoBuilder, Prof. Correia’s group was able to engineer immunogens that contain specific neutralization epitopes for RSV. “These engineered immunogens were generated via computer modeling,” explains Krey “my group then determined 3D structures of the epitope scaffolds bound to antibody fragments to ensure that these immunogens fold and bind their corresponding antibody the way predicted by the computer.” 

A cocktail formulation of three engineered immunogens was then used to vaccinate mice and nonhuman primates which resulted in the induction of a robust immune response to RSV. The engineered immunogens could be used to create an RSV vaccine which would allow for an unprecedented level of control over induced antibody specificities. “This study is not only an exciting step towards an RSV vaccine but also a brilliant proof of concept for the computational design of epitope-focused vaccines,” explains Krey “this method could be used to develop vaccines protecting from other viruses such as influenza virus, hepatitis C virus and possibly even the new corona virus SARS-CoV-2.”

F. Sesterhenn, C. Yang, J. Bonet, J. T. Cramer, X. Wen, Y. Wang, C. Chiang, L. A. Abriata, I. Kucharska, G. Castoro, S. S. Vollers, M. Galloux, E. Dheilly, S. Rosset, P. Corthésy, S. Georgeon, M. Villard, C. A. Richard, D. Descamps, T. Delgado, E. Oricchio, M. Rameix-Welti, V. Más, S. Ervin, J. F. Eléouët, S. Riffault, J. T. Bates, J. P. Julien, Y. Li, T. Jardetzky, T. Krey & B. E. Correia. De novo protein design enables the precise induction of RSV-neutralizing antibodies. Science